European Cancer Congress 2015 Conference Insight

September 2015

White Paper

The European Cancer Congress 2015

DISCLAIMER

While every care is taken to ensure the accuracy of the information contained in this material, the facts, estimates, and opinions

stated are based on information and sources which, while we believe them to be reliable, are not guaranteed. In particular, it

should not be relied upon as the sole source of reference in relation to the subject matter. No liability can be accepted by

Datamonitor, its directors, or employees for any loss occasioned to any person or entity acting or failing to act as a result of

anything contained in or omitted from the content of this material, or our conclusions as stated. The findings are Datamonitor's

current opinions; they are subject to change without notice. Datamonitor has no obligation to update or amend the research or

to let anyone know if our opinions change materially.

If you have questions about the research, data, and findings within this document you can put your questions directly to the analysts. Simply email your questions to [email protected]. To find out more about Datamonitor Healthcare, contact us at: email [email protected] phone +44 20 7551 9430 Visit our website: www.datamonitorhealthcare.com Or follow us on Twitter: @DatamonitorHC

mailto:[email protected]


http://www.datamonitorhealthcare.com/

White Paper


Datamonitor Healthcare has identified the following key highlights from the 2015 European Cancer

Congress (ECC), which was held on 25–29 September 2015 in Vienna, Austria:

Late-breaking Phase II data revealed a promising future for Roche’s programmed death ligand-1 (PD-L1)

inhibitor atezolizumab in non-small cell lung cancer (NSCLC) and bladder cancer. Interim results from the

pivotal BIRCH study have placed atezolizumab as a front-runner for the first-line treatment of PD-L1-

positive (PD-L1+) NSCLC, ahead of Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co’s Keytruda

(pembrolizumab). In bladder cancer, atezolizumab is likely to be the first programmed death-1 (PD-1)/PD-

L1 immunotherapy to reach the market and could potentially become the new standard of care.

Six of the late-breaking abstracts (LBAs) reported data for PD-1/PD-L1 drugs other than atezolizumab

across a range of different cancer types. The most prominent development was the first look at positive

data from the Phase III CheckMate 025 trial of Opdivo in previously treated renal cell cancer (RCC). The

LBAs also contained new and updated datasets for Keytruda and Opdivo in melanoma and NSCLC, while

intriguing biomarker-stratified efficacy data for AstraZeneca’s anti-PD-L1 durvalumab in NSCLC were also

presented. Merck also communicated early-phase trial data for Keytruda in the rare skin cancer Merkel cell

carcinoma (MCC). These LBAs illustrate the continuing rich investment and expansion in PD-1/PD-L1

development, and as a result it is highly likely that we can expect intense competition between many of

these drugs in the future.

Presentations of pivotal trial results for Exelixis’s multi-tyrosine kinase inhibitor Cometriq (cabozantinib) and

Bristol-Myers Squibb’s Opdivo indicate that major change is coming in the second-line treatment of RCC.

Opdivo significantly improved overall survival (OS) in comparison to Afinitor (everolimus; Novartis) and is

now likely to become the treatment of choice in the second-line setting. Cometriq’s results were not quite

as good as Opdivo’s, but they were still positive and Exelixis will be pleased at the opportunity to expand

Cometriq’s label.

Immatics revealed that the Phase III IMPRINT study of its RCC vaccine IMA901 did not meet its primary

endpoint. Immatics had hoped that the combination of IMA901 with Sutent (sunitinib; Pfizer) would produce

a synergistic immunomodulatory effect that would extend OS compared to Sutent monotherapy, and that

this would enable IMA901 to become the first approved vaccine for the treatment of RCC. Immatics has

taken the difficult decision to shift its focus onto the Adoptive Cellular Therapies (ACT) portion of its

pipeline, effectively ending the development of IMA901.

White Paper


Phase II data for Roche’s PD-L1 atezolizumab in NSCLC and bladder cancer were presented on the

morning of 27 September at ECC 2015. The data from the BIRCH and POPLAR studies for

atezolizumab in locally advanced and metastatic NSCLC and from the IMvigor 210 trial in metastatic

urothelial bladder cancer suggest a very bright future for atezolizumab. The anti-PD-L1 drug

demonstrated durable responses in pretreated advanced NSCLC, suggesting that therapies targeting

PD-L1 are comparable to those targeting PD-1. Indeed, interim results from the pivotal BIRCH study

have placed atezolizumab as a front-runner for the first-line treatment of PD-L1+ NSCLC, ahead of

Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda. Clinical responses to atezolizumab therapy

increased significantly in patients with highly expressed PD-L1 on their tumors. In bladder cancer,

atezolizumab is likely to be the first PD-1/PD-L1 immunotherapy to reach the market and could

potentially become the new standard of care.

Datamonitor Healthcare has summarized the late-breaking results for atezolizumab at ECC 2015 in

the table below.

White Paper


Summary of key atezolizumab results presented at ECC 2015

Abstract Phase (trial name; ClinicalTrials.gov identifier)

Cancer type

Patients Dosing Key efficacy data

14LBA II (POPLAR; NCT01903993)

NSCLC 287; second- and third-line locally advanced or metastatic NSCLC after platinum failure (stratified by PD-L1 expression)

Arm 1: docetaxel 75mg/m2 IV every three weeks Arm 2: atezolizumab 1,200mg IV every three weeks

ITT (all patients): Arm 1: OS = 9.7 months; PFS = 3.0 months; ORR = 15% Arm 2: OS = 12.6 months; PFS = 2.7 months; ORR = 15%High PD-L1: Arm 1: OS = 11.1 months; PFS = 3.9 months; ORR = 13% Arm 2: OS = 15.5 months; PFS = 7.8 months; ORR = 38% Medium and high PD-L1: Arm 1: OS = 7.4 months; PFS = 2.8 months; ORR = 15% Arm 2: OS = 15.1 months; PFS = 3.4 months; ORR = 22%

Low, medium, and high PD-L1: Arm 1: OS = 9.2 months;

White Paper


PFS = 3.0 months; ORR = 17% Arm 2: OS = 15.5 months; PFS = 2.8 months; ORR = 18%

No PD-L1: Arm 1: OS = 9.7 months; PFS = 4.1 months; ORR = 10% Arm 2: OS = 9.7 months; PFS = 1.7 months; ORR = 8%

16LBA II (BIRCH; NCT02031458)

NSCLC 667; first-line or higher PD-L1+ locally advanced or metastatic NSCLC

Atezolizumab 1,200mg IV every three weeks Group 1: first-line Group 2: second-line Group 3: third-line

High PD-L1: Group 1: ORR = 26%; six-month PFS = 48%; six-month OS = 79% Group 2: ORR = 24%; six-month PFS = 34%; six-month OS = 80% Group 3: ORR = 27%; six-month PFS = 39%; six-month OS = 75% Medium and high PD-L1: Group 1: ORR = 19%; six-month PFS = 46%; six-

White Paper


month OS = 82% Group 2: ORR = 17%; six-month PFS = 29%; six-month OS = 76% Group 3: ORR = 17%; six-month PFS = 31%; six-month OS = 71%

21LBA II (IMvigor210; NCT02108652)

Urothelial bladder cancer

439; locally advanced or metastatic urothelial bladder cancer Cohort 1: treatment-naïve or cisplatin-ineligible Cohort 2: disease progression after platinum treatment

Atezolizumab 1,200mg IV every three weeks

Cohort 2 results: Medium and high PD-L1: ORR = 27%; mDoR = NR; PFS = 2.1 months; OS = NR Low, medium, and high PD-L1: ORR = 18%; mDoR = NR; PFS = 2.1 months; OS = 8.0 months ITT (all patients): ORR = 15%; mDoR = NR; PFS = 2.1 months; OS = 7.9 months

ITT = intent to treat; IV = intravenous; mDoR = median duration of response; NR = not reached; NSCLC = non-small cell lung cancer; ORR = overall response rate; OS = overall survival; PD-L1 = programmed death-ligand 1; PFS = progression-free survival

Source: Besse et al., 2015; Rosenberg et al., 2015; Vansteenkiste J, et al., 2015iomarkers from a randomized phase II study (POPLAR) ECC 2015; Vienna,

White Paper


Updated final results from the POPLAR study of atezolizumab show it to be an effective treatment for

pretreated NSCLC and comparable to its potential rival Keytruda. Considering Merck submitted a

supplemental Biologic License Application (sBLA) for its anti-PD-1 therapy based on comparable data

from a Phase Ib study (KEYNOTE-001), atezolizumab’s positive data are likely to support Roche’s US

Food and Drug Administration (FDA) filing in NSCLC, which is planned for early 2016.

Speaking on 27 September, Dr Johan Vansteenkiste of University Hospital Leuven presented full

results from the Phase II POPLAR study. The randomized trial assessed atezolizumab’s safety and

efficacy compared to docetaxel in patients with locally advanced or metastatic NSCLC that had

progressed after platinum-based chemotherapy. Patients were stratified by PD-L1 expression levels

as determined by Roche’s developmental immunohistochemistry assay on tumor cells and infiltrating

immune cells. The primary endpoint was OS, and secondary endpoints included progression-free

survival (PFS), overall response rate (ORR), and safety. As with interim results previously presented

at ASCO 2015, atezolizumab was well tolerated and demonstrated clinical superiority as a second-

and third-line monotherapy compared to docetaxel. Subgroup analyses showed that PD-L1 tumor

expression correlated with response to the drug.

Data from the POPLAR study in 287 previously treated advanced NSCLC patients showed

atezolizumab improved OS by almost three months in comparison to docetaxel (12.6 months versus

9.7 months). PFS in the atezolizumab monotherapy group was 2.7 months compared to a PFS of 3.0

months in the docetaxel arm. The ORR for both groups was the same at 15%. Fewer patients in the

atezolizumab arm experienced treatment-related grade 3–4 adverse events as compared to the

docetaxel arm (11% versus 39%). Patients in the treatment arm were administered atezolizumab

intravenously at a flat dose of 1,200mg every three weeks, while those in the other arm received

75mg/m2 of docetaxel intravenously every three weeks.

NSCLC accounts for over 80% of all lung cancers, and can be further divided into squamous cell

carcinoma, adenocarcinoma, and large-cell carcinoma. NSCLC is one of the most common cancers

globally, and Datamonitor Healthcare forecasts that in the US, Japan, and five major EU markets

(France, Germany, Italy, Spain, and the UK) the incidence of NSCLC will be 505,300 patients in 2014,

rising to 569,000 in 2020.

Atezolizumab is an antibody designed to target PD-L1 on tumor cells, allowing the body’s immune

system to recognize and properly respond to the tumor. PD-1 and its ligands, PD-L1 and PD-L2, are

members of the cluster of differentiation-28 and B7 family. The cell-surface molecules of the B7 family

and the cytotoxic T-lymphocyte antigen 4 family both regulate complex signaling pathways that affect

T-cell activation, tolerance, and immunopathology. The pathways have a similar effect on T-cell

immune response but are distinct from each other.

Austria; 27 Sept 2015; 14LBA.

White Paper


These most recent data from the POPLAR study suggest that therapies targeting PD-L1 are as

efficacious as those that target PD-1. In the overall patient population, atezolizumab extended survival

by 12.6 months and delayed disease progression by 2.7 months, which is in line with data seen in

trials evaluating anti-PD-1 immunotherapies. Clinical trials assessing Opdivo and Keytruda in similar

pretreated patient populations with advanced NSCLC have demonstrated comparable results. In the

Phase III CheckMate 057 trial, Opdivo extended OS by 12.2 months and PFS by 2.3 months, while

Keytruda treatment in the Phase Ib Keynote 001 trial resulted in a 9.3-month OS benefit and a 3.0-

month PFS benefit. In the absence of head-to-head trials comparing PD-1 versus PD-L1 inhibition,

data from the POPLAR trial seem to indicate that targeting PD-L1 is a viable and similarly potent

alternative to Opdivo and Keytruda.

Datamonitor Healthcare has summarized key endpoint data in trials assessing Opdivo, Keytruda, and

atezolizumab in the table below.

Trial data from PD-1 and PD-L1 targeted therapies in pretreated advanced non-small cell lung cancer

PD-1 targeted PD-L1 targeted

Opdivo Keytruda atezolizumab

Phase III CheckMate 057 (n=292)

Phase Ib Keynote 001

(n=394)

Phase II POPLAR (n=144)

OS (months) 12.2 9.3 12.6

PFS (months) 2.3 3.0 2.7

ORR 19.2% 18% 15%

Grade 3–4 AEs 10% 9.5% 11%

AE = adverse event; ORR = overall response rate; OS = overall survival; PFS = progression-free survival

Source: Medtrack, June 2015, Copyright Informa UK; Trialtrove ®, 2015; Citeline

Interim results from the pivotal BIRCH study are the first to demonstrate clinical efficacy in treatment-

naïve PD-L1+ NSCLC patients, placing Roche as a key player in the PD-1/PD-L1 immunotherapy

arena. The results of this trial will be welcome news for Roche as atezolizumab is currently behind

Opdivo and Keytruda in development for NSCLC. Opdivo gained approval in March 2015 for

previously treated advanced squamous NSCLC, while Keytruda has recently submitted an sBLA for

pretreated PD-L1+ advanced NSCLC.

Roche has indicated that data from the BIRCH and POPLAR trials will be submitted to regulatory

bodies in support of atezolizumab’s possible approval in NSCLC. Atezolizumab received breakthrough

therapy designation in February 2015 for the treatment of patients with PD-L1+ NSCLC who have

failed prior platinum-based chemotherapy. Although it is likely that Roche will initially pursue approval

in the pretreated PD-L1+ patient population, first-line data from the BIRCH study could potentially

support a first-line approval. This means atezolizumab could reach the lucrative first-line setting ahead

of its rivals in the PD-1/PD-L1 inhibitor class.

White Paper


On 27 September, Dr Benjamin Besse of the Gustave Roussy Institute of Oncology and Paris Sud

University presented topline results from the Phase II BIRCH study. This single-arm study assessed

atezolizumab monotherapy in patients with PD-L1+ locally advanced or metastatic NSCLC. The

patients were divided into three groups according to the number of previous therapies they had

received, and the primary endpoint of the study was the ORR assessed by an independent review

facility per RECIST v1.1. The secondary endpoints of the study were duration of response, OS, PFS,

and safety. As a monotherapy, atezolizumab met its primary endpoint in all three cohorts and

demonstrated durable response rates while maintaining the same safety profile as observed in

previous studies.

Patients who had the highest levels of PD-L1 expression in all three cohorts of the trial had significant

response rates to single-agent atezolizumab. Advanced NSCLC patients with the highest expression

levels of PD-L1 who received atezolizumab as a first-line, second-line, and third-line therapy had

ORRs of 26%, 24%, and 27%, respectively. Additionally, the respective OS rates at six months were

79%, 80%, and 75%. Around 11% of patients experienced grade 3–4 treatment-related adverse

events.

Atezolizumab’s future commercial potential could be significant if Roche eventually gains approval for

the drug as a first-line therapy for PD-L1+ NSCLC. Datamonitor Healthcare anticipates that the drug

that penetrates the advanced/metastatic NSCLC first-line setting most effectively will be the one that

generates the highest commercial rewards. While it is highly likely that atezolizumab will be indicated

for patients who are PD-L1+, this patient population still represents a substantial portion of the market;

around 34% of NSCLC patients who were initially screened for the BIRCH trial were PD-L1+.

Datamonitor Healthcare expects that Roche’s early release of positive first-line BIRCH trial data

combined with an expedited FDA review may give atezolizumab the advantage over Opdivo and

Keytruda within the first-line PD-L1+ NSCLC treatment setting.

Results from the POPLAR and BIRCH trials presented at ECC 2015 demonstrated a strong correlation

between PD-L1 expression status and response to atezolizumab treatment, adding to the growing

body of evidence supporting PD-L1 as a viable biomarker. Datamonitor Healthcare expects that the

concurrent development of Roche’s companion diagnostic with atezolizumab is likely to facilitate the

drug’s regulatory approvals by identifying the patients who are most likely to benefit from this therapy.

In both the POPLAR and BIRCH studies, patients were stratified by their levels of PD-L1 expression,

which revealed that atezolizumab treatment favored tumors with high PD-L1 levels. The BIRCH study

indicated that 26% of patients with high levels of PD-L1 responded to first-line atezolizumab, while

only 19% of patients with medium levels of the ligand responded to the same treatment. Similar trends

were observed in the patient cohorts who received second- and third-line atezolizumab.

In the POPLAR study, atezolizumab in previously treated advanced NSCLC showed that increasing

levels of PD-L1 correlated with improvements in clinical endpoints. Atezolizumab therapy in patients

with no PD-L1 expression gave similar results to docetaxel and extended survival by 9.7 months. In

patients with the highest levels of the ligand, atezolizumab treatment extended OS significantly by 15.5

White Paper


months. Smaller improvements in OS, PFS, and ORR were also observed in patients with low and

medium levels of PD-L1 expression. Levels of PD-L1 expression were evaluated in tumor cells and

tumor-infiltrating immune cells by an immunohistochemistry assay being developed by Roche

Diagnostics which uses the SP142 antibody.

Datamonitor Healthcare has summarized results from the POPLAR trial based on PD-L1 levels in the

table below.

Stratification of POPLAR trial results by PD-L1 expression

TC3 or IC3 (high) (n=24)

TC2/3 or IC2/3 (medium and high) (n=50)

TC1/2/3 or IC1/2/3 (any expression) (n=93)

TC0 and IC0 (n=51)

OS (months) 15.5 15.1 15.5 9.7

PFS (months) 7.8 3.4 2.8 1.7

ORR 38% 22% 18% 8%

ORR = overall response rate; OS = overall survival; PFS = progression-free survival

Source: Medtrack, June 2015, Copyright Informa UK; Trialtrove ®, 2015; Citeline Although Datamonitor Healthcare anticipates that these correlation data are likely to support

atezolizumab’s possible regulatory approval alongside a companion diagnostic, a biomarker strategy

has yet to be determined. The clinical efficacy observed in patients with little to no PD-L1 expression

makes it unclear at this time which patients, if any, should be selected for PD-1/PD-L1 treatment.

Despite these challenges, new clinical trial data are advancing the PD-L1 biomarker field, and

Datamonitor Healthcare expects that patients and physicians will be more willing to use atezolizumab

if patient selection increases the likelihood of positive results.

Topline results from the pivotal Phase II IMvigor 210 study showed that atezolizumab is an effective

and tolerable therapy in patients with advanced platinum-refractory bladder cancer. The positive

results presented at ECC 2015 put atezolizumab ahead of Merck’s Keytruda and could mean that the

PD-L1 inhibitor may be the first targeted therapy for bladder cancer. In a traditionally hard-to-treat

patient population, atezolizumab has the potential to drastically change treatment paradigms for

advanced bladder cancer. Roche has indicated that it is planning to submit data from the IMvigor 210

study to regulatory authorities in support of atezolizumab for the treatment of patients with PD-L1+

metastatic bladder cancer. The approval process is likely to be expedited since the FDA granted

atezolizumab breakthrough therapy designation in May 2014.

On 27 September, Dr Jonathan Rosenberg of the Memorial Sloan Kettering Cancer Center presented

the first numerical results from the pivotal Phase II IMvigor210 study. In this single-arm study,

atezolizumab was assessed in patients with locally advanced or metastatic urothelial bladder cancer.

Patients were divided into two cohorts and further segmented by PD-L1 expression status. The first

cohort, for which data are still immature and were not presented at ECC 2015, included treatment-

naïve patients with locally advanced or metastatic bladder cancer, while patients with platinum-

White Paper


refractory locally advanced or metastatic bladder cancer were included in the second cohort. The

primary endpoint of the study was ORR, and secondary endpoints included duration of response, OS,

PFS, and safety. Atezolizumab met its primary endpoint in cohort 2, demonstrating an ORR of 15%

with a median PFS of 2.1 months and a median OS of 7.9 months. There were no treatment-related

deaths and atezolizumab’s safety profile remained consistent with previous safety data.

Responses to atezolizumab treatment in platinum-refractory advanced bladder cancer improved

significantly with increasing levels of PD-L1 expression. Patients who had medium to high levels of

PD-L1 expression had an ORR of 27% as compared to 18% in patients with low-to-high levels of the

protein ligand. While the median PFS at a 24-week cutoff remained unchanged between the two

patient populations (2.1 months), higher PD-L1 expression appears to confer an OS benefit. The

median OS in patients with low-to-high PD-L1 levels was eight months, while in the high PD-L1 level

patient population the OS has not yet been reached.

Overall, the pivotal data from IMvigor 210 are highly encouraging for atezolizumab’s future. The high

unmet need in advanced bladder cancer combined with the drug’s positive response rates mean that

Roche is well poised to lead and establish its presence within this indication. Dr Rosenberg

commented that there are no known agents that improve OS in metastatic urothelial bladder cancer,

and that Pierre Fabre’s Javlor (vinflunine) is the only approved therapy in Europe, which demonstrates

an ORR of only 8.6%. Atezolizumab could therefore potentially become the new standard of care and

represents a promising treatment option for patients who have had very poor prognoses. Atezolizumab

is currently in ongoing trials for treatment-naïve advanced bladder cancer as well as Phase III trials

(IMvigor 211) comparing second-line atezolizumab to chemotherapy.

White Paper


Six of the LBAs at ECC 2015 reported data for PD-1/PD-L1 immune checkpoint inhibitors other than

atezolizumab across a range of different cancer types. The most prominent development was the first

look at positive data from the Phase III CheckMate 025 trial of Opdivo in previously treated RCC,

which should guarantee the drug’s approval. The LBAs also contained new and updated datasets for

Keytruda and Opdivo in their main target indications, melanoma and NSCLC, while intriguing

biomarker-stratified efficacy data for AstraZeneca’s durvalumab in NSCLC were also presented. Merck

also communicated early-phase trial data for Keytruda in MCC, the first data for a PD-1 inhibitor for

this disease. These LBAs illustrate that since Opdivo and Keytruda were first approved for melanoma

in 2014, development of the anti-PD-1/PD-L1 class of drugs has expanded significantly, and we can

therefore expect intense competition between many of these drugs in the future.

A summary of the data presented in the LBAs can be found in the table below.

Summary of other PD-1/PD-L1 trial data presented in late-breaking abstracts at ECC 2015

Drug Abstract Phase (trial name)

Cancer type

Patients Dosing Key efficacy data

Opdivo 3LBA III (CheckMate 025)

RCC 821; advanced or metastatic disease who have received prior antiangiogenic therapy

Arm 1: IV Opdivo 3mg/kg every two weeks Arm 2: oral Afinitor 10mg once daily

Median OS: Arm 1: 25.0 months Arm 2: 19.6 months ORR: Arm 1: 25% Arm 2: 5% Median PFS: Arm 1: 4.6 Arm 2: 4.4

durvalumab 15LBA I/II NSCLC 228; advanced disease

Durvalumab monotherapy 10mg/kg every two weeks

ORR: PD-L1+/IFNγ+: 46% PD-L1+/IFNγ-: 13% PD-L1-/IFNγ+: 11% PD-L1-/IFNγ-: 3%

Keytruda 22LBA II MCC 18; advanced disease Keytruda monotherapy 2mg/kg every three weeks

ORR: 80% (out of 10 radiographically evaluable MCC patients)

Opdivo 23LBA II (CheckMate 064)

Melanoma 140; unresectable Stage III or IV melanoma, treatment-naïve or had one prior systemic therapy

Arm 1: IV Opdivo 3mg/kg every two weeks for up to six doses followed by IV Yervoy 3mg/kg every three weeks for up to four doses Arm 2: IV Yervoy 3mg/kg every three weeks for up to four doses followed by IV Opdivo 3mg/kg every two weeks for up to six

PRR: Arm 1: 35.3% (week 13) 41.2% (week 25) Arm 2: 10.0% (week 13) 20.0% (week 25) Progression rate: Arm 1: 38.2% (week 13)

White Paper


Bristol-Myers Squibb has provided the first look at data from the Phase III CheckMate 025 pivotal trial

in RCC (ClinicalTrials.gov identifier: NCT01295827). The company previously announced that the trial

had met its primary endpoint in July 2015, but the data presented at ECC 2015 now reveal the therapy

doses 61.4% (week 25) Arm 2: 38.2% (week 13) 60.0% (week 25)

Keytruda 24LBA Ib (MASTERKEY-265)

Melanoma 21; previously untreated unresectable Stage IIIb–IV with injectable lesions, no prior systemic therapy

T-VEC administered by intralesional injection 10[6] PFU/ml on day one, 10[8] PFU/ml day 22 then every two weeks + IV Keytruda 200mg every two weeks starting day 36

Median treatment dose: T-VEC: 7 doses Keytruda: 5 doses Grade 3 TEAEs: 29% Grade 4 TEAEs: 0% One patient death to PD and not due to treatment

Keytruda 33LBA I (KEYNOTE-001)

NSCLC 449; previously treated late-stage (124 of these patients had PD-L1 TPS ≥50)

IV Keytruda under three different dosing schedules: Arm A: 2mg/kg dose every three weeks Arm B: 10mg/kg dose every three weeks Arm C: 10mg/kg dose every two weeks

ORR: Arm A: 14.5% Arm B: 20.6% Arm C: 17.3% PD-L1 TPS ≥50%: 35.5% Overall: 18.7% Median PFS: Arm A: 3.3 months Arm B: 3.0 months Arm C: 2.6 months PD-L1 TPS ≥50%: 5.8 months Overall: 3.0 months Median OS: Arm A: 7.6 months Arm B: 11.1 months Arm C: 13.3 months PD-L1 TPS ≥50%: 14.0 months Overall: 10.7 months Median DOR: PD-L1 TPS ≥50%: 23.3 months Overall: 23.3 months

DOR = duration of response; IFNγ = Interferon gamma; IV = intravenous; MCC = Merkel cell carcinoma; NSCLC = non-small cell lung cancer; ORR = overall response rate; OS = overall survival; PD = progressive disease; PFS = progression-free survival; PRR = partial response rate; RCC = renal cell cancer; TEAE = treatment-emergent adverse event; TPS = tumor proportion score; T-VEC = talimogene laherparepvec

Source: BioMedTracker, Copyright 2015, reprinted with permission; ClinicalTrials.gov

White Paper


is a significant improvement over current RCC standard of care Afinitor. Opdivo is the first PD-1

inhibitor to demonstrate improved outcomes over Afinitor in previously treated advanced/metastatic

RCC; however, positive Phase III data were also seen at ECC 2015 for Exelixis’s multi-tyrosine kinase

inhibitor Cometriq. Datamonitor Healthcare expects both of these drugs will gain approval for the

treatment of RCC, and that they will be fierce competitors in the future. For more insight into Opdivo

versus Cometriq in RCC, please see below “Late-breaking abstracts presented at ECC 2015 will have

a major impact on the second-line treatment of renal cell cancer.”

The results of the Phase III CheckMate 025 study, which were also published in the New England

Journal of Medicine, demonstrated that Opdivo improved OS in previously treated

advanced/metastatic RCC patients compared to Afinitor, which is the current standard of care for

these patients. Patients in the Opdivo cohort had a median OS of 25.0 months compared with 19.6

months for Afinitor, with clinical benefits observed regardless of PD-L1 expression status. In addition,

the ORR for Opdivo was 25% compared with 5% for Afinitor. Patients treated with Opdivo also had a

higher median PFS (4.6 months Opdivo versus 4.4 months Afinitor), although the difference was not

statistically significant. The safety profile of Opdivo in this trial was consistent with what has been

previously observed: grade 3 and 4 treatment-related adverse events were observed in 19% of

patients in the Opdivo cohort and 37% of patients in the Afinitor cohort (Motzer et al., 2015).

Opdivo and Keytruda are the first PD-1 checkpoint inhibitors to reach the oncology market, with their

approvals for melanoma occurring back in 2014. Since this time, PD-1 has continued to be a key

target for immunotherapy development across skin cancer indications. LBAs at ECC 2015 highlighted

successes in the continued development of Opdivo and Keytruda for melanoma, as well as positive

data that infer the possibility of a future label expansion for Keytruda as a therapy for Merkel cell

carcinoma, a rare and aggressive form of skin cancer.

The CheckMate 064 data presented at ECC 2015 provide insight into additional treatment strategies

for the combination of Opdivo and Yervoy in advanced melanoma (ClinicalTrials.gov identifier:

NCT01783938). Bristol-Myers Squibb is already seeking approval for an Opdivo-Yervoy combination

therapy regimen for the first-line treatment of advanced melanoma (filed with the FDA in September

2015). The CheckMate 064 data demonstrate that the sequential use of Opdivo and Yervoy in

previously treated melanoma might provide patients with clinical benefit, suggesting that the company

can successfully introduce even more flexibility into the use of its two immune checkpoint drugs in the

future.

In the CheckMate 064 study, patients were either given Opdivo followed by Yervoy or Yervoy followed

by Opdivo during the induction therapy period. Following induction treatment, both cohorts received

Opdivo until disease progression or unacceptable toxicity. At the end of the 25-week induction therapy

period, 41.2% of patients who received Opdivo first in the sequence exhibited a partial response

compared to 20.0% of patients who received Yervoy first. In addition, 38.2% of patients who received

Opdivo first demonstrated disease progression versus 60.0% of patients who received Yervoy first.

During the induction periods, the incidence of high-grade adverse events was higher in patients who

received Opdivo initially, with 50% of patients exhibiting grade 3–5 adverse events, compared with

42.9% patients who were given Yervoy initially. No drug-related deaths were reported in either cohort.

White Paper


Data from the Phase Ib/II MASTERKEY-265 trial revealed that the combination of Keytruda and

Amgen’s investigational oncolytic virus T-VEC (talimogene laherparepvec) was well tolerated in

treatment-naïve advanced melanoma patients, although no efficacy data have yet been reported

(ClinicalTrials.gov identifier: NCT02263508). The MASTERKEY-265 data mark the first step in what is

a novel combination in PD-1 development so far, and could be a key point of differentiation for Merck

from competitor combination regimens in the future. T-VEC is the first oncolytic virus to be tested in

combination with a PD-1 for melanoma, and is also the first oncolytic virus to demonstrate efficacy in a

Phase III clinical trial for melanoma. Amgen previously stated in May 2015 that it would advance the T-

VEC and Keytruda combination into a Phase III pivotal trial.

On 27 September, Dr Georgina Long presented safety data from the Phase Ib portion of the

MASTERKEY-265 trial investigating the combination of Keytruda with T-VEC. Patients in this study

were initially given intralesional injections of T-VEC, with Keytruda administration beginning at day 36

of treatment and administered biweekly thereafter. T-VEC and Keytruda combination therapy was

shown to have favorable and non-overlapping adverse event profiles. Of the 21 patients who were

enrolled in the study, 29% exhibited grade 3 treatment-emergent adverse events, and no patients

exhibited grade 4 treatment-emergent adverse events. Although one patient died on study, the cause

of death was deemed to be related to progressive disease and not to treatment. No patients

discontinued therapy due to adverse events. These data demonstrate the safety of T-VEC in

combination with Keytruda at full dose.

Further developments of Keytruda for skin malignancies at ECC 2015 also included interim data from

a Phase II study investigating the therapeutic potential of Keytruda monotherapy in advanced

unresectable MCC (ClinicalTrials.gov identifier: NCT02267603). Although these are very early data

from only a small patient population, they suggest promising efficacy and will raise hopes that

Keytruda can meet some of the high unmet need in this very rare and aggressive form of skin cancer.

Of the 18 patients who received at least one dose of Keytruda, 10 had undergone at least one

radiologic and clinical response assessment. Of these 10, eight showed evidence of response to PD-1

pathway blockade (ORR = 80%). Merck speculates that the high response rate observed thus far may

in part be due to the immune response to antigens from the polyomavirus that often drives MCC.

Since the mechanism of action here is not well understood, future investigations have been planned

and follow-up results are to be presented at a later date.

MCC is a rare and highly aggressive form of skin cancer linked to ultraviolet exposure and Merkel cell

polyomavirus. The difficulty in diagnosing MCC often leads to confirmed diagnoses following

metastasis. Responses to chemotherapy in metastatic MCC are typically not durable, and up to 50%

of patients that are initially determined to be disease-free suffer disease relapse.

Late-breaking abstracts at ECC 2015 also highlighted promising PD-1 immunotherapy developments

in the NSCLC treatment space with Keytruda and durvalumab, as Merck and AstraZeneca look to

challenge Opdivo’s current position as the only PD-1/PD-L1 inhibitor approved for NSCLC.

White Paper


Dr Jean-Charles Soria presented an updated dataset from KEYNOTE-001, the study which formed the

basis of the sBLA that Merck filed for Keytruda in NSCLC in April 2015. Data from this study were last

seen in the New England Journal of Medicine in April 2015 (Garon et al., 2015). The update at ECC

2015 relates to a larger population of previously treated patients enrolled in the study and provided

more information about the drug’s efficacy at different dose levels. Datamonitor Healthcare believes

Keytruda will be approved for the treatment of patients with EGFR mutation-negative and ALK

rearrangement-negative NSCLC whose disease has progressed on or following platinum-containing

chemotherapy. These updated data should solidify Keytruda’s dosing regimen and help to ensure that

the drug can compete effectively with Opdivo, which is currently being reviewed by the FDA for

licensing in non-squamous cell NSCLC (it is already marketed for the smaller squamous-cell NSCLC

population). The FDA has granted priority review for Keytruda with a target decision date of 2 October

2015.

In KEYNOTE-001, patients were placed into one of three dosing schedules (see table above) until

confirmed progression, intolerable toxicity, or investigator decision. The results update at ECC 2015

conveyed that there is a lack of significant exposure-response relationship, and showed similar

efficacy across doses and schedules, supporting the use of 2mg/kg every three weeks for NSCLC.

However, Keytruda demonstrated particularly robust antitumor activity in patients with PD-L1 tumor

proportion score ≥50%, with ORR, median PFS, and median OS higher in this subgroup in comparison

with the total study group. Grade 3 and 4 treatment-related adverse events occurred in 10.5% of

patients, and there were three treatment-related deaths due to cardiorespiratory arrest, interstitial lung

disease, and respiratory arrest.

Phase I/II data from a trial of AstraZeneca’s anti-PD-L1 durvalumab demonstrated promising efficacy

in a very specific population of NSCLC patients (ClinicalTrials.gov identifier: NCT01693562).

Durvalumab development in NSCLC is a long way behind key rivals Opdivo and Keytruda, and

AstraZeneca has sought to differentiate the drug by looking for biomarkers other than PD-L1 for

patient selection. The data presented at ECC 2015 show that interferon-gamma (IFN-gamma) may be

a promising biomarker candidate to be used in combination with the PD-L1 biomarker for patient

selection for durvalumab in NSCLC.

On 27 September, data from a Phase I/II clinical trial of durvalumab monotherapy were presented,

looking at whether treatment response in NSCLC is correlated with high tumoral IFN-gamma mRNA,

PD-L1 protein, and combined IFN-gamma/PD-L1 protein expression. IFN-gamma-negative/PD-L1-

negative patients demonstrated the lowest ORR to durvalumab monotherapy at 3%, while IFN-

gamma-positive/PD-L1-positive patients demonstrated the highest ORR at 46%. While this

demonstrates a significant increase in response over IFN-gamma-negative/PD-L1-negative patients,

the IFN-gamma-positive/PD-L1-positive patient subgroup had the second smallest sample size of the

four subgroups, while IFN-gamma-negative/PD-L1-negative patients were the most common. Patients

expressing either PD-L1 or IFN-gamma, but not both, had similar ORRs, of 13% and 11%.

AstraZeneca is looking to further investigate the effect of IFN-gamma and PD-L1 expression on

durvalumab efficacy in NSCLC, but the data presented suggest that NSCLC patients whose tumors

have elevated IFN-gamma mRNA expression, PD-L1 protein expression, or a combination of both

may be more likely to benefit from durvalumab therapy.

White Paper


The results of pivotal Phase III trials for Exelixis’s Cometriq and Bristol-Myers Squibb’s Opdivo look set

to change the treatment algorithm for previously treated RCC patients. Late-breaking abstracts for

Cometriq’s METEOR trial and Opdivo’s CheckMate 025 trial were presented on 26 September at ECC

2015. Both trials had a positive outcome, and both Opdivo and Cometriq are likely to gain approvals

for the second-line treatment of RCC. Opdivo significantly improved OS in comparison to Afinitor and

is now likely to become the treatment of choice in this setting. Meanwhile, Cometriq’s results were not

quite as good as Opdivo’s, but they were still positive and Exelixis will be pleased at the opportunity to

expand Cometriq’s label.

Cometriq significantly improved PFS in patients with advanced or metastatic RCC in the pivotal

METEOR trial (ClinicalTrials.gov identifier: NCT01865747). This was an open-label Phase III trial

comparing Cometriq to Afinitor in patients with advanced or metastatic RCC with a clear-cell

component that had progressed after treatment with vascular endothelial growth factor receptor

(VEGFR)-targeting tyrosine kinase inhibitors (TKIs). Patients were stratified based on previous

treatments with VEGFR-targeting TKIs and prognostic risk category. The trial met the primary endpoint

of improved PFS with a median of 7.4 months for patients receiving Cometriq compared to 3.8 months

for patients receiving Afinitor, corresponding to a 42% reduction in rate of disease progression or

death. A significant increase in OS was not seen at this interim analysis, but there was a positive trend

of 33% lower death rates for Cometriq (HR: 0.67, p=0.005). The full analysis of OS is expected in

2016. Adverse events observed during the trial were similar for both arms, but 60% of patients

receiving Cometriq had a dose reduction following adverse events compared to 25% of patients

receiving Afinitor. The most common grade 3 or 4 adverse events for patients receiving Cometriq were

hypertension (15%), diarrhea (11%), and fatigue (9%).

Cometriq is a TKI with multiple targets including VEGFR, AXL receptor tyrosine kinase, and

hepatocyte growth factor receptors (c-Met). It is currently approved for the treatment of progressive,

unresectable locally advanced or metastatic medullary thyroid cancer in the US and EU.

Bristol-Myers Squibb presented impressive results from the Phase III CheckMate 025 trial

(ClinicalTrials.gov identifier: NCT01668784). Treatment with the PD-1 inhibitor Opdivo significantly

increased OS and the drug had a favorable safety profile compared to Afinitor. The Phase III trial

enrolled patients with advanced or metastatic RCC with a clear cell component, previously treated with

one or two antiangiogenic therapies. Exclusion criteria included more than three prior treatments with

systemic therapy, brain metastases, and prior treatment with an mTOR inhibitor. Following advice from

an objective independent data monitoring committee, the study was terminated early (in June 2015)

because the primary endpoint of OS had been met. The median OS for patients treated with Opdivo

was 25.0 months compared to 19.6 months for patients treated with Afinitor. Grade 3 or 4 treatment-

related adverse events occurred in 19% of the patients treated with Opdivo compared to 37% treated

with Afinitor, and the most common grade 3 or 4 adverse event associated with treatment with Opdivo

was fatigue (2%). In this study no correlation between PD-1 expression and response to treatment

with Opdivo was seen.

Opdivo is a fully human immunoglobulin G4 PD-1 immune checkpoint inhibitor that binds to the

checkpoint receptor PD-1 expressed on activated T-cells. It is approved for the treatment of

White Paper


unresectable or metastatic melanoma in the US and EU, and for the treatment of metastatic squamous

cellNSCLC in the US.

A summary of Cometriq’s METEOR trial and Opdivo’s CheckMate 025 trial can be found in the table

below.

Overview of key data from the METEOR and CheckMate 025 trials

Phase (trial name; ClinicalTrials.gov identifier)

Sample size

Target patients

Study design

Dosing Key results

Phase III (METEOR; NCT01865747)

658 Advanced or metastatic clear-cell carcinoma, previously treated with VEGFR inhibitors

Multicenter, open-label, randomized

Arm 1: 60mg Cometriq orally once daily Arm 2: 10mg Afinitor orally once daily

PFS: Arm 1: 7.4 months Arm 2: 3.8 months HR: 0.58 (p<0.001) ORR: Arm 1: 21% Arm 2: 5% (p<0.001) Discontinuation due to adverse events: Arm 1: 9% Arm 2: 10% Grade 3 or 4 adverse events: Arm 1: 68% Arm 2: 58%

Phase III (CheckMate 025; NCT01668784)

821 Advanced or metastatic clear-cell carcinoma, previously treated with one or two antiangiogenic agents

Multicenter, open-label, randomized

Arm 1: Opdivo 3mg/kg IV every two weeks Arm 2: 10mg Afinitor orally once daily

OS: Arm 1: 25.0 months Arm 2: 19.6 months (p=0.0018) HR for death: 0.73 (p=0.002) PFS: Arm 1: 4.6 months Arm 2: 4.4 months HR: 0.88 (p=0.11) ORR:

White Paper


Arm 1: 25% Arm 2: 5% OR: 5.98 (p<0.001) Discontinuation due to adverse events: Arm 1: 8% Arm 2: 13% Grade 3 or 4 adverse events: Arm 1: 19% Arm 2: 37%

HR = hazard ratio; IV = intravenous; OR = odds ratio; ORR = overall response rate; OS = overall survival; PFS = progression-free survival

Source: Choueiri et al., 2015; Motzer et al., 2015

The results from the METEOR and CheckMate 025 trials will have a major impact on the treatment

algorithm for second-line RCC therapy. Both Opdivo and Cometriq provided a significant benefit

compared to treatment with Afinitor, and both drugs are likely to gain approvals for this treatment

setting. An editorial in the New England Journal of Medicine that accompanied the publication of these

results recommended that both drugs be used for previously treated advanced RCC. The editorial

suggests that Opdivo should now be the treatment of choice for patients who have disease

progression while they are receiving VEGF-targeted therapy and that Cometriq is a salvage treatment

for patients whose tumors progress during VEGF therapy (Quinn and Lara, 2015). In the absence of

an OS benefit and because of its side-effect profile, Cometriq will not precede Opdivo in the treatment

sequence and will instead be used at third-line or later.

Cometriq’s results were overshadowed by Opdivo’s, but Exelixis will still be pleased by the success of

the METEOR trial and the opportunity to gain approval in another indication. Following the failure of

Cometriq’s development for metastatic castration-resistant prostate cancer, it was crucial that

Cometriq achieve a positive outcome in the METEOR trial. Cometriq will now compete with other

VEGF inhibitors in the crowded RCC market, but will have the advantage of showing significantly

improved PFS in comparison to Afinitor, while the final analysis of the data in 2016 could also reveal

an OS advantage. Undoubtedly the rewards for Exelixis would have been much greater in the

absence of Opdivo’s results, but Cometriq at least has some strong data and will generate some

revenue as a salvage treatment in previously treated patients. Exelixis has stated that it is on track to

complete its New Drug Application filing by the end of 2015, and a European filing is expected to

follow in early 2016.

White Paper


At ECC 2015, Immatics revealed that the Phase III IMPRINT study of its RCC vaccine IMA901 did not

meet its primary endpoint. Immatics had hoped that the combination of IMA901 with Sutent would

produce a synergistic immunomodulatory effect that would extend OS compared to Sutent

monotherapy, and that this would enable IMA901 to become the first approved vaccine for the

treatment of RCC. However, the negative outcome of IMPRINT has driven Immatics to make a difficult

decision to shift its focus onto the ACT portion of its pipeline, effectively ending the development of

IMA901. The company is likely to now quickly advance its ACT candidates from preclinical to clinical

development in a bid to not get left behind by other companies that are already highly active in this

space.

On 27 September at ECC 2015, Dr Brian Rini, professor of medicine at the Cleveland Clinic Taussig

Cancer Center, presented the results from the pivotal Phase III IMPRINT trial (ClinicalTrials.gov

identifier: NCT01265901) of IMA901 in advanced or metastatic RCC. The study failed to meet its

primary endpoint of OS: median OS was 33.1 months in the IMA901 vaccination plus Sutent group,

but median OS in the control group (Sutent alone) had not yet been reached (HR: 1.34; p=0.08). In the

favorable-risk patient subpopulation, OS was comparable between the IMA901 and control arms (33.7

months vs not reached, HR: 0.82; p=0.59). Intermediate-risk patients displayed a longer OS benefit in

the control group (not yet reached) versus the IMA901 vaccination group (27.8 months; HR: 1.52;

p<0.05). A blinded independent central review found that PFS was similar between treatment and

control groups (15.1 vs 15.1 months; HR: 1.05; p=0.62), but an investigator-initiated assessment found

PFS to be longer in the control group compared to the IMA901 vaccination group (17.9 vs 15.1

months; HR: 1.18; p=0.19). This led to a higher median exposure of Sutent in the control group (13.7g

control vs 11.2g IMA901). IMA901-specific CD8 T-cell responses from treatment with the IMA901 and

Sutent combination were reduced by a factor of three compared to the response observed in IMA901’s

Phase II monotherapy trial. IMA901 displayed a favorable safety profile, with mild injection site

adverse events accounting for the most common treatment-related side effects.

In the open-label, randomized, controlled Phase III IMPRINT study, 339 human leukocyte antigen A2-

positive metastatic RCC patients were randomized 3:2 to receive either 10 intradermal vaccinations of

IMA901 plus 75µg of granulocyte-macrophage colony-stimulating factor and 50mg of Sutent, or Sutent

alone. A single injection of cyclophosphamide at 300mg/m2 was administered three days prior to the

first vaccination of IMA901 to reduce regulatory T-cell levels. The patients were stratified by risk group

(Heng risk criteria), nephrectomy status, and region (US, Western EU, and Central Eastern EU).

IMA901 is a fully synthetic cancer vaccine consisting of 10 tumor-associated peptides (TUMAPS) that

are found to be overexpressed on the tumor cells of RCC patients. TUMAPS work by activating

cytotoxic T-cells (class I TUMAPS) and helper T-cells (class II TUMAPS) to target tumor cells. The

helper T-cells assist cytotoxic T-cells by secreting cytokines, and the cytotoxic T-cells directly kill tumor

cells. Thus, IMA901 acts to prime a patient’s own T-cells so that they can recognize TUMAPS

presented on tumor cells, which may otherwise have evaded the immune system.

Early-phase data presented at the 2010 ESMO Cancer Congress suggested IMA901 had promising

efficacy in previously treated RCC patients. The Phase II Study 202 trial (ClinicalTrials.gov identifier:

NCT00523159) tested IMA901 in second-line advanced/metastatic RCC patients who relapsed after

previous treatment with cytokines or kinase inhibitors. Median OS was 19.8 months in all second-line

White Paper


patients (previously treated with cytokines) who received IMA901. The disease control rates at six

months were 31% for post-cytokine patients and 14% in post-TKI patients.

In a press release following the presentation of the IMPRINT data, Dr Carsten Reinhardt, chief medical

officer of Immatics, expressed his disappointment at the failure of the study to meet its primary

endpoint (Immatics, 2015). He stated that the company will continue to evaluate the data, but that it

will now shift its focus towards developing its ACT technology, in partnership with the MD Anderson

Cancer Center. This signifies that development of IMA901 is likely finished, and investors and market

commentators will now be left to worry about the fate of the company’s other pipeline cancer vaccines.

Immatics is developing two other cancer vaccines for colorectal cancer and glioma, which are in

Phase II and Phase I clinical trials, respectively. It is also unclear what effect this will have on

Immatics’ partnership with Roche for TUMAP vaccines in NSCLC, gastric cancer, and prostate cancer.

These vaccines are still presently in preclinical stages.

By choosing to focus on its ACT program, Immatics is joining a host of other biotechnology companies

that are pioneering various cell-based techniques in the immuno-oncology space. The most

developmentally advanced ACT therapies are the personalized chimeric antigen receptor T-cell (CAR-

T) therapies. Juno’s JCAR015 and Novartis’s CTL019 have both achieved promising results in early-

phase clinical trials in acute lymphoblastic leukemia. Both drugs have also received breakthrough

therapy designation for this indication from the FDA. Another CAR-T therapy, Kite’s KTE-C19, has

demonstrated preliminary efficacy in diffuse large B-cell lymphoma (a subtype of non-Hodgkin’s

lymphoma) and chronic lymphocytic leukemia. Pfizer and Cellectis are also partnering on the

development of next-generation allogeneic ACT therapies, representing an “off-the-shelf” approach to

cellular immunotherapy. Immatics’ ACT program will focus on developing both autologous and

allogeneic ACT therapies.

White Paper


Besse B, et al. (2015) Phase II, single-arm trial (BIRCH) of atezolizumab as first-line or subsequent

therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC). ECC

2015; Vienna, Austria; 27 September 2015; 16LBA.

Choueiri TK et al. (2015) Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. The

New England Journal of Medicine, 25 September 2015 <DOI>10.1056/NEJMoa1510016</DOI>.

Garon EB, et al. (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. The New

England Journal of Medicine, 372(21), 2018–28 <DOI>10.1056/NEJMoa1501824</DOI>.

Immatics (2015) Immatics announces results of IMPRINT phase 3 clinical trial investigating the

addition of IMA901 to standard first-line therapy with sunitinib for advanced/metastatic RCC. Available

from: http://immatics.com/immatics-announces-results-of-imprint-phase-3-clinical-trial-investigating-

the-addition-of-ima901-to-standard-first-line-therapy-with-sunitinib-for-advancedmetastatic-rcc/

[Accessed September 27 2015].

Motzer RJ et al. (2015) Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. The New

England Journal of Medicine, 25 September 2015 <DOI>10.1056/NEJMoa1510665</DOI>.

Quinn DI, Lara PN (2015) Renal-Cell Cancer — Targeting an Immune Checkpoint or Multiple Kinases.

The New England Journal of Medicine, 25 September 2015 <DOI>10.1056/NEJMe1511252</DOI>.

Rosenberg J, et al. (2015) Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial

carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210). ECC 2015; Vienna,

Austria; 27 September 2015; 21LBA.

Vansteenkiste J, et al. (2015) Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung

cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II

study (POPLAR). ECC 2015; Vienna, Austria; 27 September 2015; 14LBA.

http://immatics.com/immatics-announces-results-of-imprint-phase-3-clinical-trial-investigating-the-addition-of-ima901-to-standard-first-line-therapy-with-sunitinib-for-advancedmetastatic-rcc/

http://immatics.com/immatics-announces-results-of-imprint-phase-3-clinical-trial-investigating-the-addition-of-ima901-to-standard-first-line-therapy-with-sunitinib-for-advancedmetastatic-rcc/

White Paper


Bringing you a clearer, richer and more responsive view of the pharma & healthcare market.

Complete market coverage

Our independent research and analysis provides extensive coverage of major disease areas,

companies and strategic issues, giving you the perspective to identify opportunities and

threats arising from shifting market dynamics and the insights to respond with faster, more

effective decision-making.

Unique expert capabilities

With teams located across developed and emerging pharma markets, we are uniquely

placed to understand local healthcare trends and provide accurate and reliable

recommendations. By working closely with our partners at MedTrack, Citeline, SCRIP

Intelligence and Informa Healthcare, our experts are able to share data and resources to

produce the most authoritative and robust market intelligence.

Cutting-edge delivery

Available through single reports or via subscription to our state-of-the art online intelligence

service that features intuitive design and interactive capabilities, our analysis offers the

definitive platform to enhance your product management, market assessment and strategic

planning.

To find out more about Datamonitor Healthcare, please contact us at:

email [email protected]

phone +44 20 7551 9430

website: www.datamonitorhealthcare.com

Twitter: @DatamonitorHC


Documents

European Cancer Congress 2015 Conference Insight