Cabometyx-Tecentriq Combo Leads to Lasting Response in Men with Advanced PC, Phase 1b Trial Data Shows

Cabometyx-Tecentriq Combo Leads to Lasting Response in Men with Advanced PC, Phase 1b Trial Data Shows

The combination of Cabometyx (cabozantinib) and Tecentriq (atezolizumab) is safe and shows clinically meaningful activity, leading to lasting responses in men with metastatic castration-resistant prostate cancer (mCRPC), a Phase 1b trial shows.

The trial’s findings were presented in a poster, “Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of Cohort 6 of the COSMIC-021 Study,” at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium (ASCO GU 2020), held recently in San Francisco.

The global, open-label COSMIC-021 Phase 1b trial (NCT03170960) is evaluating the safety, tolerability, and preliminary efficacy of Exelixis’ Cabometyx in combination with Genentech’s Tecentriq in people with different types of solid cancers. The trial also is assessing the combination’s pharmacokinetic properties — how a drug is absorbed, distributed, and metabolized in the body, then eliminated.

In total, the study aims to enroll up to 1,732 participants with 12 types of solid tumors, including CRPC, kidney, liver, bladder, lung, and breast cancer.

Its initial dose-escalation phase assessed the optimal dosage of Cabometyx in combination with a fixed dose of Tecentriq. The trial’s first part is followed by an expansion phase, in which participants will receive the selected dose to continue studying its safety and efficacy.

Throughout the trial’s first part, Tecentriq was given intravenously (into the vein) every three weeks at a dose of 1,200 mg. The completed dose-escalation phase, which involved 12 patients with advanced kidney cancer, determined that Cabometyx should be administered at a daily dose of 40 mg, given in oral tablets. In this part of the trial, half of the participants responded to the combination therapy, with one even attaining a complete response of total cancer eradication.

Exelixis more recently announced that the mCRPC group of COSMIC-021 — those participants with advanced prostate cancer — had been expanded based on preliminary encouraging safety and effectiveness data.

That group was increased from 30 to 130 men. More information on contacts and recruitment locations can be found here.

The new interim data presented at the ASCO GU meeting showed that, in the group of men with prostate cancer, the combination therapy of Cabometyx and Tecentriq continues to show clinically meaningful activity.

The analysis was based on data from 44 men — median age of 70 — with mCRPC whose disease had progressed while on hormone therapy. More than half (52%) of the patients had received at least two prior lines of hormonal therapy, and nearly a third (27%) had undergone treatment with the chemotherapy agent docetaxel.

At the study’s start, or baseline, 34% of the participants had cancer that had spread to other organs (called visceral metastases), while 61% had cancer that had spread to lymph nodes located outside the pelvic region (or extrapelvic lymph node metastases).

At a median follow-up of 12.6 months, approximately a third (32%) of the patients had responded to the combo therapy and nearly half (48%) achieved a state of stable disease. That yielded a disease control rate of 80%. Among those responding to the treatment, two (4.5%) achieved a complete response and 12 (27%) a partial response of partial cancer eradication.

Among the 36 participants with high-risk clinical features — the presence at the study’s start of cancer in other organs and/or in the lymph nodes outside the pelvic region — approximately a third (33%) responded to the combination therapy.

The median duration, or length of response among all men who responded to the combo therapy was 8.3 months, and the median time of treatment was 6.3 months.

No new safety concerns with the therapy were identified in this group of men. The most common treatment-related adverse events (TRAEs) were fatigue, reported by 57% of participants, nausea, which occurred in 48% of patients, and decreased appetite, reported by 45%. In addition, there were reports of diarrhea (39%), palmar-plantar erythrodysesthesia (PPE) (32%), and vomiting (32%). PPE, or hand-foot syndrome, causes redness, swelling, and pain on the palms of the hands and/or the soles of the feet.

A fatal , or grade 5 event of dehydration was reported in a 90-year-old patient. Only 7% of the participants discontinued treatment due to adverse events unrelated to disease progression.

“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,” Neeraj Agarwal, MD, professor at the Huntsman Cancer Center at University of Utah, and a COSMIC-021 investigator, said in a press release.

“We look forward to additional results as the trial progresses,” Agarwal said.

“We’re happy to share these encouraging results from the metastatic CRPC cohort from COSMIC-021, our first trial evaluating the combination of cabozantinib and atezolizumab,” said Gisela Schwab, MD, president of product development and medical affairs and chief medical officer at Exelixis.

“We look forward to receiving data from the most recent expansion of this CRPC cohort while we are also preparing for the initiation of a Phase 3 pivotal trial in this indication. We are excited about the emerging data in metastatic CRPC and elsewhere and the potential of combining cabozantinib with immunotherapies in this and other difficult-to-treat tumor types,” Schwab added.

Exelixis now is awaiting future data from the remaining patients in the trial’s mCRPC group, as well as regulatory feedback from the U.S. Food and Drug Administration. Depending on those results, the company is planning to request accelerated approval from the FDA for the combination therapy of Cabometyx and Tecentriq in 2021.