Therapy Areas: Oncology
Exelixis Releases Results from Two Analyses Evaluating Effect of PD-L1 Expression or Prior Treatment with Checkpoint Inhibitors on Efficacy of Cabozantinib in Patients with Advanced Renal Cell Carcinoma
22 October 2018 - - US-based Exelixis, Inc. (NASDAQ: EXEL) has published results from two analyses evaluating the effect of PD-L1 expression or prior treatment with immune checkpoint inhibitors on the efficacy of cabozantinib in patients with advanced renal cell carcinoma, the company said.

The findings are being presented this week at the European Society for Medical Oncology 2018 Congress being held October 19–23 in Munich, Germany.

An analysis of data from the CABOSUN and METEOR trials demonstrated that cabozantinib improved clinical outcomes regardless of PD-L1 status in patients with advanced RCC, relative to sunitinib or everolimus, the respective comparator arms for each trial.

The late-breaking abstract [LBA 34] is being presented TODAY in the Genitourinary Tumors, Non Prostate poster discussion session starting at 2: 45 p.m. CEST (local Munich time).

Tumor tissue from 110 patients in the CABOSUN trial and 306 patients in the METEOR trial were evaluated to determine whether PD-L1 expression (≥1% of tumor cells) predicted outcomes or response to treatment.

The findings showed that PD-L1 expression was associated with shorter median progression-free survival and overall survival in both METEOR and CABOSUN. Treatment with cabozantinib, however, improved PFS and OS compared with everolimus (METEOR) and sunitinib (CABOSUN) in both PD-L1 positive and PD-L1 negative patients.

An additional analysis evaluating the activity of cabozantinib in 69 patients with advanced RCC who progressed on immune checkpoint inhibitors [abstract 879P] will be presented by lead investigator Bradley McGregor, M.D., Dana-Farber Cancer Institute, at ESMO on Monday, October 22 in a poster display session at 12: 45 p.m. CEST.

This retrospective analysis found that cabozantinib was active in patients previously treated with immune checkpoint inhibitors, either alone or in combination with anti-VEGF or other therapies.

At a median follow-up of 12 months, objective response rate was 33%, disease control rate was 79% and the one-year overall survival rate was 53%.

On May 23, 2016, Exelixis announced that the phase 2 CABOSUN study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment.

The CABOSUN study was conducted by The Alliance for Clinical Trials in Oncology and was sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) under the Cooperative Research and Development Agreement with Exelixis for the development of cabozantinib.

These results were first presented by Dr. Toni Choueiri at the European Society for Medical Oncology (ESMO) 2016 Congress and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016).

In June 2017, a blinded independent radiology review committee confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS.

Results from the IRC review were presented by Dr. Toni Choueiri at the ESMO 2017 Congress.

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria.

Patients were randomised 1: 1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate and safety.

Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate- or poor-risk per the IMDC criteria (Heng, JCO, 2009).

Prior systemic treatment for RCC was not permitted.

METEOR was an open-label, event-driven trial of 658 patients with advanced RCC who had failed at least one prior VEGFR TKI therapy.

The primary endpoint was PFS in the first 375 patients treated. Secondary endpoints included OS and objective response rate in all enrolled patients.

The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia.

Patients were randomized 1: 1 to receive 60 mg of CABOMETYX daily or 10 mg of everolimus daily and were stratified based on the number of prior VEGFR TKI therapies received and on MSKCC risk criteria. No cross-over was allowed between the study arms.

METEOR met its primary endpoint of significantly improving PFS and significantly improved the objective response rate compared with everolimus.

These data were presented at ESMO 2015 and published in The New England Journal of Medicine.

Carbometyx also demonstrated a statistically significant and clinically meaningful increase in OS in the METEOR trial.

Cabozantinib benefit in OS was robust and consistent across all pre-specified subgroups. In particular, benefit was observed regardless of risk category, location and extent of tumor metastases, and tumor MET expression level.

These results were presented on June 5, 2016 at the ASCO annual meeting and concurrently published in The Lancet Oncology.
Login
Username:

Password: