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

Colorectal Cancer Clinical Trial

Official title: A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

Status Active, not recruiting

Clinical Trial 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.

Clinical Trial Description

• Dose Escalation Stage: to determine the schedule and maximum tolerated dose (MTD) and/or recommended Expansion Stage dose of cabozantinib when taken in combination with a standard dosing regimen of atezolizumab (1200 mg infusion, once every 3 weeks).

• Expansion Stage: to determine the preliminary efficacy (objective response rate [ORR] per RECIST 1.1) and safety of the recommended combination dose of cabozantinib with atezolizumab in eighteen tumor-specific cohorts including subjects with advanced UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N, and DTC.

• Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent cabozantinib in UC, NSCLC, and CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy

• Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent atezolizumab in CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Castration-resistant Prostate Cancer
• Colorectal Cancer
• Differentiated Thyroid Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Head and Neck Cancer
• Hepatocellular Carcinoma
• Lower Esophageal Cancer
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Renal Cell Carcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

• NCT number: NCT03170960
• Study type: Interventional
• Source: Exelixis
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 5, 2017
• Completion date: August 2024