Title of articleOlaparib maintenance monotherapy in PSR ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design

Article details

AuthorsAndres M Poveda, Richard Davidson, Christopher Blakeley &Alvin Milner

Article URLwww.futuremedicine.com/doi/10.2217/fon-2019-0343

Trial registration numberNCT03402841

Determine the e�cacy of olaparib maintenance monotherapy by assessment of TFST, TDT and CT-FI, as well as evaluation of investigator-assessed PFS according to tumor HRD status and HRQoL. The trial will also evaluate OS and the safety and tolerability of olaparib

Primary objectives/rationale

Key eligibility criteria

Determine the e�cacy, by investigator-assessed PFS (according to modi�ed RECIST v1.1), of olaparib maintenance monotherapy in patients with non-gBRCA m PSROC

Primary objective

Secondary objectives

Global Open-label

Multicenter Phase III, single-arm

~250 patients (actual sample size 279)

Non-randomized

?~250

Planned study period = 30 months (PFS analysis); OS analysis at ~36 months

Age ≥18 years

Glossary

CT-FI: Chemotherapy-free interval; HRQoL: Health-related quality of life; Non-gBRCA m: Non-germline BRCA1 and/or BRCA2-mutated; OS: Overall survival; PFS: Progression-free survival; PSROC: Platinum-sensitive relapsed ovarian cancer; RECIST v1.1: Response Evaluation Criteria in Solid Tumors; TDT: Time to treatment discontinuation or death; TFST: Time to �rst subsequent therapy or death

P3

Key eligibility criteria

Treatment: olaparib tablets 300 mg (2 x 150 mg) twice daily; oral administration

Treatment will continue until disease progression, unacceptable toxicity, or any other protocol-speci�ed criterion for withdrawal occurs

Histologically diagnosed, relapsed, high-grade serous (including primary peritoneal and/or fallopian tube cancer) or high-grade endometrioid ovarian cancer

Documented non-gBRCA m status

Completed at least two previous courses of platinum-containing therapy:- For the penultimate chemotherapy course before enrollment in the study: • Patient is platinum-sensitive after this treatment • Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab- For the last chemotherapy course immediately before enrollment in the study: • Patients must be, in the opinion of the investigator, in response (partial or complete), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy) with no evidence of rising CA-125, after completing this course • No bevacizumab treatment allowed

Eastern Cooperative Oncology Group performance status 0–1

Tumour sample collected before enrollment

Adequate liver, renal, hepatic and bone marrow function (absolute neutrophil count ≥1.5 × 109/l; platelet count ≥100 × 109/l; hemoglobin ≥10 g/dl)

No prior treatment with a PARP inhibitor is allowed

18+

Study design and treatment including planned sample size, planned study period and study procedures

2019 Future Medicine Ltd

Title of articleLenvatinib plus everolimus or pembrolizumab vs sunitinib in advanced renal cell carcinoma: study design and rationale

Article details

AuthorsViktor Grünwald, Thomas Powles, Toni K Choueiri, Thomas E Hutson, Camillo Porta, Masatoshi Eto, Cora N Sternberg, Sun Young Rha, Corina E Dutcus, Alan Smith, Lea Dutta, Kalgi Mody & Robert J Motzer

Article URLwww.futuremedicine.com/doi/10.2217/fon-2018-0745

Trial registration numberNCT02811861

Compare ORR, OS, safety and tolerability, HRQoL, PFS on next line of therapy between treatment arms; characterize the pharmacokinetics of lenvatinib when coadministered with everolimus or pembrolizumab; and assess the pharmacokinetic/ pharmacodynamic relationship between exposure and e�cacy, biomarkers, and safety

Primary objectives/rationale

Key eligibility criteriaStudy design and treatment including plannedsample size, planned study period and study procedures

Demonstrate that lenvatinib plus everolimus or lenvatinib plus pembrolizumab is superior compared with sunitinib monotherapy in improving PFS in the �rst-line treatment of patients with advanced RCC

Primary objective

Secondary objectives

Global Open-label

Multicenter Phase III, 3-arm

Randomized patients: 1050

Randomized 1:1:1

?1050

Patients will be randomized centrally by an interactive voice- and web-response system in a 1:1:1 ratio to open-label treatment with oral lenvatinib 18 mg/day plus oral everolimus 5 mg/day, oral lenvatinib 20 mg/day plus pembrolizumab 200 mg iv. Q3W or oral sunitinib 50 mg/day on a schedule of 4 weeks on and 2 weeks o�

Age ≥18 years

Outcome measures/end points

Secondary end points ORR by independent imaging review using RECIST v1.1; OS; safety and tolerability and HRQoL

Glossary

HRQoL: Health-related quality of life; MSKCC: Memorial Sloan Kettering Cancer Center; ORR: Overall response rate; OS: Overall survival; Q3W: Every 3 weeks; PFS: Progression-free survival; RCC: Renal cell carcinoma

Primary end point PFS by independent imaging review using RECIST v1.1

P3

Key eligibility criteria

Randomization will be strati�ed according to geographic region (Western Europe and North America versus other), and MSKCC prognostic groups (favorable, intermediate, or poor risk)

Patients will continue to receive treatment until disease progression, unacceptable toxicity, patient request, withdrawal of consent, or study termination.

Histological or cytological con�rmationof RCC with a clear cell component, and documented evidence of advanced disease

≥1 measurable target lesion according to RECIST v1.1, a Karnofsky performance status ≥70, adequately controlled blood pressure (with or without antihypertensive medications), and adequate renal, bone marrow, blood coagulation, and liver function

No prior systemic anticancer therapy for RCC

No radiation therapy within 21 days prior to the �rst dose of study drugs, except for palliative radiotherapy to bone lesions, which is permitted if completed 2 weeks prior to the start of study treatment

Patients with untreated central nervous system metastases or those who had received a live vaccine within 30 days of the planned �rst dose of study drug(s) are also excluded

Exploratory end points include PFS in the lenvatinib plus pembrolizumab arm by immune-related RECIST (irRECIST), duration of response, disease control rates, clinical bene�t rates, and the relationship between blood biomarkers and e�cacy outcomes

18+

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