Study of Cabozantinib Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Summary

This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer/gastroesophageal junction cancer/lower esophageal cancer (GC/GEJC/LEC), colorectal cancer (CRC), head and neck (H\&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Subjects enrolled in the SAC cohorts and SAA cohort may receive combination treatment with both cabozantinib and atezolizumab after they experience radiographic progressive disease per the Investigator per RECIST 1.1. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

Timeline

Start

2017-09-05

Primary completion

2023-02-21

Completion

2027-09-30

Publications

• Pal SK, Loriot Y, Necchi A, Singh P, Castellano D, Pagliaro L, Suarez C, McGregor BA, Vaishampayan UN, Hauke RJ, Powles T, Van Herpen CML, Courtney KD, Dreicer R, Sudhagoni R, Schwickart M, Andrianova S, Agarwal N. COSMIC-021 Phase Ib Study of Cabozantinib Plus Atezolizumab: Results from the Locally Advanced or Metastatic Urothelial Carcinoma Cohorts. J Clin Oncol. 2025 May 10;43(14):1650-1662. doi: 10.1200/JCO-24-01675. Epub 2025 Feb 18.
• Li D, Loriot Y, Burgoyne AM, Cleary JM, Santoro A, Lin D, Aix SP, Garrido-Laguna I, Sudhagoni R, Guo X, Andrianova S, Paulson S. Cabozantinib plus atezolizumab in previously untreated advanced hepatocellular carcinoma and previously treated gastric cancer and gastroesophageal junction adenocarcinoma: results from two expansion cohorts of a multicentre, open-label, phase 1b trial (COSMIC-021). EClinicalMedicine. 2023 Dec 21;67:102376. doi: 10.1016/j.eclinm.2023.102376. eCollection 2024 Jan.
• Agarwal N, McGregor B, Maughan BL, Dorff TB, Kelly W, Fang B, McKay RR, Singh P, Pagliaro L, Dreicer R, Srinivas S, Loriot Y, Vaishampayan U, Goel S, Curran D, Panneerselvam A, Schwickart M, Choueiri TK, Pal S. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Lancet Oncol. 2022 Jul;23(7):899-909. doi: 10.1016/S1470-2045(22)00278-9. Epub 2022 Jun 9.
• Pal SK, McGregor B, Suarez C, Tsao CK, Kelly W, Vaishampayan U, Pagliaro L, Maughan BL, Loriot Y, Castellano D, Srinivas S, McKay RR, Dreicer R, Hutson T, Dubey S, Werneke S, Panneerselvam A, Curran D, Scheffold C, Choueiri TK, Agarwal N. Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study. J Clin Oncol. 2021 Nov 20;39(33):3725-3736. doi: 10.1200/JCO.21.00939. Epub 2021 Sep 7.

Drugs

Indications