ASCO GU 2019: Phase Ib (COSMIC-021) Trial of Cabozantinib in Urothelial Carcinoma or Cabozantinib in Combination with Atezolizumab in patients with Urothelial Carcinoma, Castrate Resistant Prostate Cancer or Renal Cell Carcinoma

San Francisco, CA ( Cabozantinib is a VEGFR2/MET/AXL tyrosine kinase inhibitor with anti-angiogenic, anti-tumor growth and immune regulation properties. Recent studies have demonstrated that cabozantinib may enhance response to immune checkpoint inhibitors (ICI) such as PD-1 and PD-L-1 inhibitors. It is currently approved for patients with advanced or metastatic RCC (mRCC) and has been used in combination therapies for the treatment of renal cell carcinoma (RCC), urothelial carcinoma (UC), and castrate-resistant prostate cancer (CRPC). Atezolizumab is a monoclonal anti-PD-L-1 antibody and is approved for patients with advanced or metastatic UC who progress on platinum-based chemotherapy, in platinum-ineligible patients and in PD-L1 + platinum-ineligible patients.

COSMIC-021 is an international, multi-institutional, open-label, phase 1b trial that will assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of the combination of cabozantinib and atezolizumab in patients with mRCC, mUC, and CRPC. The study has two stages: the dose escalation stage and the expansion stage. In the Dose Escalation Stage, a recommended cabozantinib dose will be established for the combination with standard-dose atezolizumab. In the expansion stage, 18 tumor-specific cohorts (with 30 patients per cohort) will be enrolled in order to evaluate the safety and efficacy of the combination treatment. Two exploratory single-agent cabozantinib (SAC) cohorts will also be enrolled with UC or non-small cell lung cancer (NSCLC) patients.

The seven genitourinary cohorts are as follows: (1) treatment naïve clear cell RCC; (2) non-clear cell RCC, treatment naïve or following systemic anticancer therapy; (3) UC after prior platinum-based therapy; (4) treatment naïve cisplatin-ineligible UC; (5) treatment naïve cisplatin-eligible UC; (6) UC after prior ICI therapy and (7) CRPC after prior enzalutamide and/or abiraterone.

The study began in 2017 and is estimated to come to completion in 2020 after enrollment of 1000 patients. The primary outcome measure of the dose escalation stage is to determine the maximum tolerated dose (MTD) and/or recommended dose of cabozantinib when taken in combination of standard-dose atezolizumab. The primary outcome measure of the dose expansion stage is to determine the preliminary efficacy by estimating the objective response rate (ORR) by RECIST 1.1. The secondary outcome measures are to assess the safety of combination therapy and define adverse events and serious adverse events.

Presented by: Sumanta Pal, MD, Associate Clinical Professor, Department of Medical Oncology & Therapeutics Research, Co-director of City of Hope's Kidney Cancer Program

Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, @selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA