ESMO: Exelixis lays out promising early Cabometyx combo data in prostate cancer, but key discrepancies persist

Exelixis, having already reported one surprising flop over the summer with its combo of Cabometyx and Roche’s Tecentriq in liver cancer, is hoping for a different outcome in difficult-to-treat prostate cancer. Now, the company is touting promising early-stage data it thinks will help it dodge another pitfall.

In Exelixis’ phase 1b COSMIC-021 trial, its tyrosine kinase inhibitor Cabometyx coupled with Roche’s immuno-oncology med Tecentriq demonstrated a clinically meaningful result in a cohort of patients with metastatic castrate-resistant prostate cancer (mCRPC) who were previously treated with Pfizer and Astellas’ Xtandi (enzalutamide) or Johnson & Johnson’s Zytiga (abiraterone acetate), according to details shared at the European Society for Medical Oncology annual congress. 

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To Exelixis, the showing has been strong enough to take to the FDA for feedback over next steps for a regulatory filing in the high-risk group and, potentially, an accelerated approval. A company spokesperson wasn’t available to comment on the status of those discussions or other questions related to its forthcoming presentation.

Specifically, Exelixis defines high-risk patients as those with measurable visceral or extra-pelvic lymph node metastases. Out of the 132 mCRPC patients enrolled in study's cohort 6, 101 were considered high risk, according to Exelixis.

Of the high-risk patients, 27% responded to the treatment and two showed a complete response after a median follow-up of roughly 15 months, according to the study’s investigator. Overall, about 23% of the prostate cancer patients responded to the combo, and three reported complete responses.

However, as RBC Capital analysts pointed out when Exelixis first revealed preliminary findings in late May, those figures were “substantially” lower when assessed by an independent, blinded radiology committee. In the company's ESMO presentation, the committee pegged the combo’s overall response rate closer to 15% and the high-risk response at 18%.

Given that the other metrics were similar between the investigator and the committee, RBC said it was possible that the discrepancy stemmed from how the pair graded a patient’s response through CT and MRI scans.

As for the key high-risk group, patients were able to go 6.8 months without their cancer progressing, although that figure dropped to 5.7 months for the entire cohort. Overall survival for those using the combo was just over 18 months, according to the presentation.

Exelixis reported that side effects were manageable, although just over half of patients experienced grade 3 and 4 side effects that could be severe or life threatening, according to the presentation. Over half of patients experienced diarrhea, 42% had nausea, 43% felt fatigued and roughly a third had a decreased appetite.

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There are about 250,000 new cases of prostate cancer now being diagnosed per year, the American Cancer Society estimates. Chances of surviving are grim when the cancer spreads beyond the prostate, and patients don’t respond to androgen-suppression therapies, with a median survival of less than two years, according to Exelixis. 

The details surrounding Exelixis’ COSMIC-021 trial cohort come after the drugmaker’s Cabometyx-Tecentriq combo had a surprising stumble in a phase 3 liver cancer trial in late June. Pitted against Bayer’s Nexavar, Exelixis said the duo was likely not going to reach statistical significance and prolong patients’ lives in previously untreated hepatocellular carcinoma, the most common type of liver cancer. 

That hasn’t stopped Exelixis. The drugmaker still plans to take the data to the FDA given that the trial met the co-primary endpoint of progression-free survival.