A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)

Official Title

A PHASE 1B/2 OPEN-LABEL STUDY TO EVALUATE SAFETY, CLINICAL ACTIVITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH OTHER CANCER IMMUNOTHERAPIES IN PATIENTS WITH ADVANCED MALIGNANCIES

Summary:

This is a Phase 1b/2 dose-optimization study to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary antitumour activity of avelumab (MSB0010718C) in combination with other cancer immunotherapies in patients with locally advanced or metastatic solid tumours. The primary purpose is to assess the safety and early signs of efficacy of various avelumab combinations with other cancer immunotherapies, optimizing dosing regimens as appropriate, in a limited series of indications.

Trial Description

Primary Outcome:

• Number of participants with Dose-Limiting Toxicities (DLT)
• Objective Response - Number of Participants With Objective Response

Secondary Outcome:

• Cmax of avelumab (MSB0010718C)
• Cmax of PF-05082566
• Ctrough of avelumab (MSB0010718C)
• Ctrough of PF-05082566
• Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C)
• Anti-Drug Antibody (ADA) levels of PF-05082566
• Time to Tumour Response (TTR)
• Duration of Response (DR)
• Progression-Free Survival (PFS)
• Overall Survival (OS)
• Tumour tissue biomarkers
• Cmax of PF-04518600
• Anti-Drug Antibody (ADA) levels of PF-04518600
• Ctrough of PF-04518600

This is a Phase 1b/2, open-label, multi-centre, multiple-dose, safety, clinical activity, PK, and PD study of avelumab in combination with other immune modulators in adult patients with locally advanced or metastatic solid tumours (eg, non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), gastric cancer, platinum resistant ovarian cancer, bladder cancer, small cell lung cancer (SCLC) and progressing tenosynovial giant cell tumour/pigmented villonodular synovitis (TGCT/PVNS) . In Phase 1b, this includes patients whose disease has progressed on standard of care therapy or for whom no standard therapy is available. In Phase 2, enrollment criteria regarding prior treatment(s) received varies by tumour type. Incorporation of the other immune modulators into this study is based on preclinical and clinical data supportive of single-agent tolerability and potential clinical benefit, as well as non-clinical data suggesting safety, tolerability and clinical benefit of the agent(s) in combination with avelumab. Combinations of avelumab plus other immune modulator(s) to be evaluated are as follows:

• Combination A: avelumab plus utomilumab (4-1BB agonist mAb)

• Combination B: avelumab plus PF-04518600 (OX40 agonist mAb)

• Combination C: avelumab plus PD 0360324 (M-CSF mAb)

• Combination D: avelumab plus utomilumab plus PF-04518600

• Combination F: avelumab plus CMP-001 (TLR9 agonist) and avelumab plus CMP-001 plus utomilumab and avelumab plus CMP-001 and PF-04518600 Each combination will be studied individually in 2 study parts: 1) a Phase 1b Lead-in part to evaluate safety, and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and RP2D (if applicable), of the combination, and 2) a Phase 2 part to evaluate efficacy and further evaluate safety of the selected dose from the Phase 1b portion in pre-specified patient populations.

View this trial on ClinicalTrials.gov