Drug Development

Exelixis, Bristol-Myers mount pivotal study of Cabo/Opdivo combo for frontline kidney cancer

Fouad Namouni, Bristol-Myers Squibb

Just days after reviewing a promising start combining Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) with Cabometyx (cabozantinib), Exelixis is rolling out a late-stage partnership that will take the combo into a pivotal Phase III study as a frontline therapy for kidney cancer. And not satisfied with the one checkpoint tie-up, the South San Francisco-based biotech also announced a deal this morning to collaborate with Roche on a combination of its drug Tecentriq (atezolizumab) and cabo.

Exelixis $EXEL and Bristol-Myers $BMY are splitting the costs on their Phase III program, which will explore the combo, either alone or with Yervoy (ipilimumab), in kidney cancer as well as bladder cancer, hepatocellular carcinoma and possibly other tumor types. The early stage work was done under an agreement with the NCI’s Cancer Therapy Evaluation Program. This new pact marks Exelixis’ and Bristol-Myers’ first R&D collaboration in I/O.

Exelixis shares jump 6% on the news.

Ten days ago Exelixis unveiled the first snapshot of efficacy data for the double and triple combo in genitourinary tumors.

Investigators concluded:

Among the 43 patients who were evaluable for response, the objective response rate (ORR) for all tumor types was 30 percent (38 percent for the doublet dosing schedule and 18 percent for the triplet dosing schedule), with a 7 percent complete response (CR) rate and a 23 percent partial response (PR) rate. Stable disease (SD) was reported in 56 percent of patients. The ORR for patients with mUC was 38 percent, and 2 of 16 patients achieved a CR, while 2 patients with squamous cell carcinoma of the bladder had objective responses (1 CR and 1 PR). In the mUC cohort, 15 of 16 patients had a CR, PR or SD as their best response.

“Combining our Immuno-Oncology portfolio with promising agents which target different and complementary pathways is a key component of our strategy to improve treatment outcomes for patients,” said Fouad Namouni, MD, head of Development, Oncology, Bristol-Myers Squibb.

Bristol-Myers — the one-time leader in checkpoint inhibitors — is continuing to double down on Opdivo after an embarrassing series of setbacks in lung cancer badly dented its share price.

Leerink’s Michael Schmidt gave the deal a quick thumbs up, happy to see Exelixis take a shot at moving to frontline use.

This is positive news since these collaborations could potentially significantly expand Cabometyx commercial potential beyond 2nd lien RCC, while limiting additional incremental R&D spend which is in-line with mgmt.’s business strategy. While some of the Cabometyx opp’ty beyond the currently approved indication in 2nd line RCC is reflected in our model and valuation, the scope of these collaborations exceeds our expectations and could potentially increase the regulatory and commercial probability-of-success for Cabometyx in 1st line RCC. Our estimates are under review.

Exelixis is also sponsoring a Phase Ib study that pairs cabo with Tecentriq in fighting solid tumors. With enrollment planned to begin in the middle of this year, investigators have a shot at later opening up four treatment cohorts: one for previously untreated advanced clear cell renal cell carcinoma and three cohorts of urothelial carcinoma, including platinum eligible first-line patients, first- or second-line platinum ineligible patients and patients previously treated with platinum-containing chemotherapy.

The data from these studies can be made available to Exelixis’ partners, Ipsen and Takeda, for their own development initiatives, provided they opt in. So far though only Ipsen has signed up.

“People with advanced genitorurinary malignancies are in need of additional treatment options that can improve clinical outcomes,” said Sumanta Kumar Pal, MD, co-director, Kidney Cancer Program at City of Hope, and principal investigator in the study. “The combined approach of tyrosine kinase inhibition with cabozantinib alongside immune-checkpoint inhibition has already shown promise in an early phase 1 clinical trial. We look forward to further examining this potential with cabozantinib plus atezolizumab to treat a range of genitourinary and other tumors.”



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