Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies

Official Title

A Multicentre, Open-label, Phase 1b/2 Study To Evaluate Safety And Efficacy Of Avelumab (msb0010718c) In Combination With Chemotherapy With Or Without Other Anti-cancer Immunotherapies As First-line Treatment In Patients With Advanced Malignancies

Summary:

This is a Phase 1b/2, open label, multicentre, safety and clinical activity study of avelumab in combination with chemotherapy as first-line treatment of adult patients with locally advanced or metastatic solid tumours. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and in combination with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial (bladder) cancer (UC) (Cohort A2). As more information is learned about other anti-cancer immunotherapy agents, in future portions of the study, avelumab may be combined with chemotherapy and other anti-cancer immunotherapy agents in patients with these same or different tumour types.

Trial Description

Primary Outcome:

  • Phase 1b lead-in: Number of patients with dose-limiting toxicities in first 2 cycles
  • Confirmed objective response (OR)
Secondary Outcome:
  • Progression-Free Survival (PFS)
  • Duration of Response (DR)
  • Time to Tumour Response (TTR)
  • Overall Survival (OS)
  • Plasma concentrations of cisplatin
  • Plasma concentrations of gemcitabine
  • Plasma concentrations of pemetrexed
  • Plasma concentrations of carboplatin
  • Serum concentrations of avelumab
  • Anti-Drug Antibody (ADA) levels of avelumab
  • Mutational load within baseline tumour tissue
  • PD-L1 expression in baseline and on-treatment tumour tissue
This is a Phase 1b/2, open label, multicentre, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with chemotherapy with or without other anti-cancer immunotherapies, as first-line treatment of adult patients with locally advanced or metastatic solid tumours. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial cancer (UC) (Cohort A2). Given the growing preclinical and clinical indications that combinations of anti-cancer immunotherapies potentially improve patient outcomes compared to results seen with single agents, in portions of the study to be added in the future, avelumab will be evaluated in combination with both standard-of-care chemotherapy and other anti-cancer immunotherapies in patients with advanced malignancies. Each cohort in the study will consist of a Phase 1b lead-in portion to evaluate safety and a Phase 2 cohort expansion to evaluate safety and efficacy. In the Phase 1b safety lead-in portion, up to 12 patients will be enrolled into each cohort and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of treatment. If investigational products administration in a cohort is deemed safe in the Phase 1b lead-in, enrollment will be expanded into the Phase 2 cohort expansion. Up to approximately 40 patients in each cohort (including those enrolled in the Phase 1b lead-in and those enrolled in the Phase 2 cohort expansion) will be enrolled and treated with avelumab plus chemotherapy in the initial portion of the study and, in future portions of the study, with avelumab plus chemotherapy with or without other anti-cancer immunotherapies.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society