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

  • STATUS
    Recruiting
  • End date
    Dec 17, 2022
  • participants needed
    1732
  • sponsor
    Exelixis
Updated on 17 April 2021
cancer
measurable disease
carcinoma
breast cancer
lung cancer
progressive disease
cabozantinib
esophageal cancer
gastric cancer
cancer treatment
solid tumour
solid tumor
triple negative breast cancer
metastatic solid tumor
ovarian cancer
transitional cell carcinoma
atezolizumab
advanced urothelial carcinoma
mammogram
cancer of the ovary
lung carcinoma

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.

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

Details
Condition Non-Small Cell Lung Cancer, Adenocarcinoma, Ovarian disorder, Colorectal Cancer, Endometrial Carcinoma, Malignant neoplasm of kidney, Rectal disorder, Uterine Cancer, Breast Cancer, Ovarian Cancer, Transitional cell carcinoma, Renal Cell Carcinoma, HEPATIC NEOPLASM, HEPATOCELLULAR CARCINOMA, Gastropathy, Gastric Cancer, head and neck cancer, Diet and Nutrition, Chronic Diarrhea, Stomach Discomfort, Skin Wounds, Chronic Shoulder Pain, Vaginal Atrophy, Adverse Effects, Drugs, Injection Port, Breast Cancer - HER2 Positive, Anal Dysplasia, Primary Immunodeficiency, Pediatric Health, Near-Sighted Corrective Surgery, Colon Cancer Screening, Rectal Disorders, Colon cancer; rectal cancer, Ovarian Function, Peripheral Arterial Occlusive Disease, Triple Negative Breast Cancer, Gastroesophageal Junction Adenocarcinoma, Brain Function, Adenocarcinoma of the Gastroesophageal Junction, Differentiated Thyroid Cancer, Gastric Carcinoma, Recurrent Respiratory Papillomatosis, Recurrent Ovarian Cancer, Castration Resistant Prostate Cancer, Razor Bumps (Pseudofolliculitis Barbae), Metastatic Triple-Negative Breast Cancer, Kidney Cancer, Endometrial Cancer, Liver Cancer, Malignant Adenoma, Stomach Cancer, Renal Cell Cancer, Renal Cancer, Lower Esophageal Cancer, Urothelial Carcinoma, clear cell renal cell carcinoma, colorectal neoplasm, ovarian carcinomas, cancer, ovarian, cancer ovarian, cancer of the ovary, gastric cancers, colorectal cancers, nsclc, cancer of the head and neck, ovarian tumors, liver cell carcinoma, cancer, colorectal, colorectal tumor, tumors, colorectal
Treatment Cabozantinib, Atezolizumab
Clinical Study IdentifierNCT03170960
SponsorExelixis
Last Modified on17 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent
Dose-Escalation Stage
Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy
Expansion Stage
Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N cancer, and DTC as outlined above)
Measurable disease per RECIST 1.1 as determined by the investigator
Tumor tissue material available (archival or recent tumor biopsy)
Recovery to baseline or Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
Age eighteen years or older on the day of consent
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Adequate organ and marrow function
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception
Female subjects of childbearing potential must not be pregnant at screening

Exclusion Criteria

Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5, 7, 9, 11, 17, 19 and 20. Other restrictions regarding prior therapy may apply
Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment
Concomitant anticoagulation with oral anticoagulants
Subject is receiving systemic steroid therapy (>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment
Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C)
Pregnant or lactating females
Previously identified allergy or hypersensitivity to components of the study treatment formulations
Diagnosis of another malignancy within 2 years before first dose of study treatment
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