Printer Friendly

Exelixis Updates Phase 1b COSMIC-021 Trial of Cabozantinib in Combination with Atezolizumab in Patients with Advanced Solid Tumors.

M2 PHARMA-July 16, 2019-Exelixis Updates Phase 1b COSMIC-021 Trial of Cabozantinib in Combination with Atezolizumab in Patients with Advanced Solid Tumors

(C)2019 M2 COMMUNICATIONS

- Two original cohorts are being expanded and four new cohorts are being added to the protocol for COSMIC-021, the phase 1b trial of cabozantinib (CABOMETYX) in combination with atezolizumab (TECENTRIQ) in patients with locally advanced or metastatic solid tumors, US-based Exelixis, Inc. (NASDAQ: EXEL) said.

Based on preliminary encouraging activity, as determined by response assessment per Response Evaluation Criteria in Solid Tumors (version 1.1) (RECISTv1.1), and safety data, the original immunotherapy-refractory non-small cell lung cancer (NSCLC) and metastatic castration-resistant prostate cancer cohorts are being expanded to 80 patients each.

Additionally, four new cohorts consisting of two expansion and two exploratory cohorts are being added to COSMIC-021.

The two new expansion cohorts will evaluate the combination of cabozantinib and atezolizumab in patients with metastatic CRPC who have received prior enzalutamide or abiraterone therapy, with or without prior docetaxel therapy.

The two new exploratory arms evaluating single-agent cabozantinib and single-agent atezolizumab in patients with metastatic CRPC are being added to determine the individual contribution of each therapy.

With these additions, the trial now includes 20 expansion cohorts and four exploratory cohorts and aims to enroll up to 1,732 patients with advanced or metastatic solid tumors such as renal cell carcinoma and urothelial carcinoma, among others.

The primary objective in the expansion stage of this trial remains to determine the objective response rate in each cohort.

After reviewing the safety and efficacy data, as determined by response assessment per RECISTv1.1, of patients enrolled in the immunotherapy-refractory NSCLC cohort, 50 additional patients (80 total) with stage IV non-squamous NSCLC who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease will be enrolled at the recommended dose of cabozantinib 40 mg plus atezolizumab 1,200 mg.

An exploratory single-agent cabozantinib cohort was previously added to the protocol. This cohort evaluates the activity of cabozantinib (60 mg daily) in 30 patients with stage IV non-squamous NSCLC who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.

After reviewing the safety and efficacy data, as determined by response assessment per RECISTv1.1, of patients enrolled in the metastatic CRPC cohort, 50 additional patients with metastatic CRPC (80 total) who have histologically or cytologically confirmed adenocarcinoma of the prostate are being enrolled at the recommended dose of cabozantinib 40 mg plus atezolizumab 1,200 mg.

Prior treatment with one novel hormonal therapy for castration-sensitive prostate cancer or metastatic CRPC is permitted. Patients may have previously received docetaxel for metastatic CSPC but no other approved or experimental systemic therapies apart from one poly (ADP-ribose) polymerase inhibitor for metastatic prostate cancer.

A combination-therapy expansion cohort with 30 patients with metastatic CRPC who have histologically or cytologically confirmed adenocarcinoma of the prostate after prior treatment with one NHT for CSPC or metastatic CRPC are being added.

Patients may have previously received docetaxel for metastatic CSPC but no other approved or experimental systemic therapies apart from one PARP inhibitor for metastatic prostate cancer.

30 patients with metastatic CRPC who have histologically or cytologically confirmed adenocarcinoma of the prostate who received docetaxel for metastatic CRPC and at least one NHT for CSPC or metastatic CRPC will be enrolled in a new combination-therapy expansion cohort at the recommended dose of cabozantinib 40 mg plus atezolizumab 1,200 mg.

An exploratory single-agent cabozantinib cohort and exploratory single-agent atezolizumab cohort with patients with metastatic CRPC who have histologically or cytologically confirmed adenocarcinoma of the prostate after prior treatment with one NHT for CSPC or metastatic CRPC are being added.

Patients may have previously received docetaxel for metastatic CSPC but no other approved or experimental systemic therapies apart from one PARP inhibitor for metastatic prostate cancer. The single-agent cabozantinib cohort will initially enroll up to 30 patients, and the single agent atezolizumab cohort will initially enroll up to 10 patients.

COSMIC-021 is a multicenter, phase 1b, open-label study that is divided into two parts: a dose-escalation phase and an expansion cohort phase.

The dose-escalation phase was designed to enroll patients either with advanced RCC with or without prior systemic therapy or with inoperable, locally advanced, metastatic or recurrent UC (including renal, pelvis, ureter, urinary bladder and urethra) after prior platinum-based therapy.

Ultimately, all patients enrolled in this stage of the trial were patients with advanced RCC.

The dose-escalation phase of the study determined the optimal dose of cabozantinib to be 40 mg daily when given in combination with atezolizumab (1200 mg infusion once every 3 weeks). These results were presented at the European Society for Medical Oncology 2018 Congress.

In the expansion phase, the trial is enrolling 20 expansion cohorts in 12 tumor types: RCC, UC, NSCLC, CRPC, triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, hepatocellular carcinoma, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and differentiated thyroid cancer.

Up to a total of 1,720 patients may enroll in this phase of the trial: each expansion cohort will initially enroll approximately 30 patients, and up to 10 cohorts may expand enrollment up to 1,000 additional patients in the expansion phase.

In three exploratory cohorts, approximately 30 patients each with advanced UC, CRPC, or NSCLC will be treated with cabozantinib as a single-agent.

In a fourth exploratory cohort, approximately 10 patients with advanced CRPC will be treated in a single-agent atezolizumab cohort. Exploratory cohorts have the option to be expanded up to 80 patients (cabozantinib) and 30 patients (atezolizumab) total.

Founded in 1994, Exelixis is an oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialisation of new medicines for difficult-to-treat cancers.

Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need.

((Comments on this story may be sent to info@m2.com))
COPYRIGHT 2019 Normans Media Ltd.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2019 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Publication:M2 Pharma
Date:Jul 16, 2019
Words:1007
Previous Article:Gilead and Galapagos Enter 10-Year Research and Development Collaboration.
Next Article:Boehringer Ingelheim Acquires Swiss Biotechnology Firm AMAL Therapeutics.
Topics:

Terms of use | Privacy policy | Copyright © 2020 Farlex, Inc. | Feedback | For webmasters