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Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

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Page 1: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Page 2: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Moderator

Mary Jo Laffler US Head of Commercial Content, Pink Sheet & Scrip

Panelists

Dr. Peter P. Lee, MD, Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA

Robert Jeng, PhD, Senior Scientific Analyst for Biomedtracker

Allison Bruce, Principal Analyst in Oncology for Citeline

Zachary McLellan, Analyst in Oncology for Datamonitor Healthcare

Page 3: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 3

A phase III trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naive patients with advanced melanoma (MEL)

• NIVO 1 mg/kg Q3W + IPI 3 mg/kg Q3W for 4 doses (followed by NIVO 3 mg/kg Q2W), NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo, until progression or unacceptable toxicity

• Pts stratified by PD-L1 status, BRAF mutation status, and M-stage

• Treatment-naïve pts (N=945) were randomized

• At ≥18 months follow-up, median PFS continued to be significantly longer for NIVO+IPI and NIVO vs IPI (P<0.001), and was numerically longer for NIVO+IPI vs NIVO alone

• Median duration of response in 181/314 (57.6%) NIVO+IPI responders has not been reached, and was 22.3 and 14.4 months in 138/316 (43.7%) NIVO and 60/315 (19.0%) IPI responders

Conclusions:

NIVO+IPI and NIVO alone continue to demonstrate superior clinical activity vs IPI monotherapy. NIVO+IPI appears to have greater efficacy than either agent alone, regardless of PD-L1 expression or BRAF mutation status.

CheckMate 067: PD-1 & CTLA4 HR, hazard ratio; NR, not reached. aExploratory endpoint.

Page 4: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 4

A phase I/II study of pembrolizumab (pembro) in combination with dabrafenib (D) and trametinib (T) for BRAF-mutant advanced melanoma

• 1:1 to pembro 2 mg/kg IV Q3W with D 150 mg orally BID + T 2 mg orally daily or placebo + D + T

• unresectable or metastatic stage III/IV BRAFV600E/K- mutant melanoma and no prior therapy are to be randomized

• Primary end point is PFS; secondary end points are ORR, response duration, and OS

• Recruitment in KEYNOTE-022 is ongoing

Conclusions:

Phase I: The approved doses of pembro in combination with D + T administered concurrently provided a manageable toxicity profile in pts with BRAF-mutant melanoma. A phase II study will further evaluate safety and efficacy of this triplet combination as first-line therapy for BRAF-mutant melanoma.

Phase II: ongoing

KEYNOTE-022:

Page 5: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 5

Immunotherapy Triplet Combinations by Phase and Status

Source: Trialtrove® as of June 2016

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

I

I/II

II

Terminated

Planned

Open

Completed

Page 6: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Moderator

Mary Jo Laffler US Head of Commercial Content, Pink Sheet & Scrip

Panelists

Dr. Peter P. Lee, MD, Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA

Robert Jeng, PhD, Senior Scientific Analyst for Biomedtracker

Allison Bruce, Principal Analyst in Oncology for Citeline

Zachary McLellan, Analyst in Oncology for Datamonitor Healthcare

Analyzing ASCO 2016: Questions for the panel

Questions can be submitted in the chat box at any time

Page 7: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 7

A phase III trial of palbociclib with letrozole compared with letrozole alone in postmenopausal women with ER+/HER2– advanced breast cancer

• P (oral 125 mg/d; 3 wks on/1 wk off) + L (2.5 mg/d continuously) or PLB + L every 28 days until disease progression.

• 666 postmenopausal pts with no prior systemic therapy for advanced breast cancer were randomized 2:1.

• Median PFS was 24.8 mo (P+L) vs 14.5 mo (PLB+L) (HR=0.58 [0.46–0.72], P<0.000001). ORR was improved with P+L (42% vs 35%, P=0.031; 55.3% vs 44.4% in pts with measurable disease [P=0.013]). CBR was 85% vs 70% (P<.0001).

• Serious AEs occurred in 19.6% of patients in the P + L arm versus 12.4% with PBL + L. 36% of patients required dose reduction.

Conclusions:

Significant clinical benefit in ER+/HER2– advanced breast cancer pts who had not received prior systemic therapy for their advanced disease.

Confirms PFS benefit from PALOMA-1.

Longest front-line improvement in median PFS to date for advanced ER+ breast cancer pts.

Phase III studies ongoing.

PALOMA-2: CDK4/6

Page 8: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 8

A phase II study of abemaciclib, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease

• Abemaciclib (200 mg) administered orally on a continuous schedule every 12 hours until unacceptable toxicity or progressive disease.

• 132 pts treated, >90% visceral metastases.

• Median of 3 lines of prior therapy for metastatic disease, including a median of 2 lines of chemotherapy for advanced disease.

• Confirmed ORR (per RECIST v1.1) was 19.7%, the clinical benefit rate (CR + PR + SD ≥ 6 mos) was 42.4%, median PFS was 6.0 mos, and median OS was 17.7 mos. The disease control rate (CR + PR + SD) was 67.4%.

• Most common G3 AE was diarrhea at 20%.

• 49% of patients required at least 1 dose reduction.

Conclusions:

Abemaciclib demonstrates single agent activity in heavily pretreated, refractory HR+/HER2- metastatic breast cancer. Treatment was mostly well tolerated, allowing continuous exposure to therapy.

Phase III MONARCH 2 and MONARCH 3 trials are ongoing.

MONARCH1: CDK4/6

Page 9: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Moderator

Mary Jo Laffler US Head of Commercial Content, Pink Sheet & Scrip

Panelists

Dr. Peter P. Lee, MD, Chair, Department of Immuno-Oncology at City of Hope Comprehensive Cancer Center, CA

Robert Jeng, PhD, Senior Scientific Analyst for Biomedtracker

Allison Bruce, Principal Analyst in Oncology for Citeline

Zachary McLellan, Analyst in Oncology for Datamonitor Healthcare

Analyzing ASCO 2016: Questions for the panel

Questions can be submitted in the chat box at any time

Page 10: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 10

A phase II pivotal randomized study of brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC)

• oral BRG at 90 mg qd (arm A) or 90 mg qd for 7 d followed by 180 mg qd (arm B)

• pts were randomized (arm A/B, n=112/n=110)

• Median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy for advanced disease.

• As of 7 Dec 2015, 63%/74% (A/B) were ongoing; median time on treatment was 25 wk/23 wk. Investigator-assessed ORR in A: 46% (95% CI 36–55%; 39 confirmed responses + 12 single responses awaiting confirmation), including 1 confirmed complete response (CR); ORR in B: 54% (95% CI 44–63%; 49 confirmed responses + 10 single responses awaiting confirmation), including 5 confirmed CRs. Median PFS in A/B: 8.8 mo/11.1 mo (events per arm [A/B]: 44/25).

Conclusions:

In each arm, BRG yielded substantial responses and robust PFS, with an acceptable safety profile. A ph 3 study of BRG at 90 mg qd for 7 d followed by 180 mg qd vs CRZ in TKI-naive, advanced ALK+ NSCLC is planned.

ALTA: ALK inhibitor

Page 11: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Pharma intelligence | informa 11

Randomized open-label phase III trial of alectinib (ALC) versus crizotinib (CRZ) in ALK-inhibitor naive ALK-positive NSCLC

• ALK+ NSCLC pts were randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.)

• 207 pts were enrolled

• The PFS HR of ALC arm to CRZ arm was 0.34 (99.6826% CI: 0.17-0.70, stratified log-rank p<0.0001). Median PFS was not reached (95% CI: 20.3-Not Estimated) in ALC arm while it was 10.2 months (95%CI: 8.2-12.0) in CRZ arm.

• Superiority in PFS had been demonstrated

Conclusions:

At J-ALEX IA, ALC demonstrated significantly prolonged PFS compared with CRZ and was well tolerated with a favorable AE profile.

J-ALEX: ALK inhibitor

Page 12: Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Analyzing ASCO 2016: Developments, takeaways, and implications from the conference

Thank you for joining us today.

Please email questions or comments to [email protected].