NCT03170960

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

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 914 (actual)
• Sponsor: Exelixis · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

Conditions

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

Interventions

Type	Name	Description
DRUG	cabozantinib	Supplied as 60-mg and 20-mg tablets; administered orally daily at dose levels of 20 mg, 40 mg, or 60 mg.
DRUG	atezolizumab	Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).
DRUG	cabozantinib	Supplied as 60-mg and 20-mg tablets; administered orally daily at the Cohort Review Committee-determined recommended dose from the Dose Escalation Stage
DRUG	cabozantinib	Supplied as 60-mg and 20-mg tablets; administered orally daily at 60 mg qd

Timeline

• Start date: 2017-09-05
• Primary completion: 2023-02-21
• Completion: 2027-09-30
• First posted: 2017-05-31
• Last updated: 2025-08-17

Locations

124 sites across 9 countries: United States, Australia, Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom

Regulatory

• FDA-regulated drug study