Exelixis bounces back with new prostate cancer data

Exelixis has announced that its lead drug cabozantinib, in combination with Roche’s Tecentriq, demonstrated encouraging results in a phase 1 prostate cancer trial.

The COSMIC-021 trial evaluated the combination treatment in patients with locally advanced or metastatic castration-resistant prostate cancer (CRPC), whose disease had progressed on prior novel hormone therapy.

Exelixis previously attempted to tackle prostate cancer with cabozantinib back in 2014, but the drug was unable to show any survival benefit on its own. Following the disappointing results, Exelixis was forced to slash its workforce by 70%, in order to buy time to bring its other pipeline projects to fruition.

It seems like that sacrifice was worth it, with cabozantinib in combination with PD-1 inhibitor Tecentriq (atezolizumab) hitting the primary endpoint of an improved objective response rate. The ORR was 32% –  that includes two complete responses and 12 partial responses.

Importantly, among the 36 patients with high-risk clinical features – including visceral metastases and/or extra-pelvic lymph node metastases – the ORR was 33%.

"Emerging data suggests a tolerable safety profile and encouraging efficacy for this combination that may hold promise for these patients with limited treatment options, potentially providing patients with more time before the need for treatment with chemotherapy. We look forward to additional results as the trial progresses," said Neeraj Agarwal, professor at Huntsman Cancer Center, University of Utah and an investigator of the trial.

Cabozantinib, a c-MET and VEGFR2 inhibitor, is already approved under the brand name Cometriq as a treatment for progressive, metastatic medullary thyroid cancer in the US and Europe.

It is also approved for use under the name Cabometyx in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) – net product revenues from the entire franchise are expected to be between $725m and $775 this year, according to Exelixis’ recently reported financial guidance for 2020.

Exelixis is also testing cabozantinib in a host of other clinical trials, including a phase 3 trial in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) in previously untreated advanced or metastatic RCC.

It is also testing cabozantinib in combination with Tecentriq in another setting – previously untreated HCC. Analysis from a phase 3 trial of this combination are due as early as the second half of 2020.

Exelixis intends to file the cabozantinib/Tecentriq combination with the FDA for accelerated approval in metastatic CRPC by 2021.