Pivotal Phase 3 CONTACT-02 Trial of Cabozantinib/Atezolizumab in mCRPC Initiated

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Exelixis, Inc. has launched the phase 3 CONTACT-02 trial examining cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer who have received prior treatment with 1 novel hormonal therapy.

Exelixis, Inc, has launched the phase 3 CONTACT-02 trial (NCT04446117) examining cabozantinib (Cabometyx) in combination with atezolizumab (Tecentriq) in patients with metastatic castration-resistant prostate cancer (CRPC) who have received prior treatment with 1 novel hormonal therapy.1

“As many patients with advanced CRPC who have progressed on a novel hormonal therapy wish to avoid or delay chemotherapy, more treatment options are needed,” Gisela Schwab, MD, president of Product Development and Medical Affairs and chief medical officer of Exelixis said stated in a recent press release.

“We are encouraged by the positive early-stage results for the combination of cabozantinib and atezolizumab seen for [patients with] prostate cancer in cohort 6 of the COSMIC-021 trial, and we are pleased to begin this pivotal trial that will further evaluate how the combination may improve outcomes for these patients as part of our ongoing partnership with Roche,” Schwab added.

In the global, multicenter, randomized phase 3 trial, investigators plan to enroll approximately 580 patients spanning 250 sites. To be eligible for enrollment, patients must have mCRPC and have received previous treatment with only 1 novel hormonal therapy, such as abiraterone acetate (Zytiga), apalutamide (Erleada), darolutamide (Nubeqa), or enzalutamide (Xtandi).2 Additionally, patients must be aged ≥18 years, have an ECOG performance status of 0 or 1, and adequate organ and marrow function based on laboratory assessments done within 21 days prior to randomization.

If patients received any prior treatment for mCRPC with a nonhormonal therapy; if they were given abiraterone within 1 week, cyproterone within 10 days, or flutamide (Eulexin), nilutamide (Nilandron), bicalutamide (Casodex), enzalutamide, or other androgen-receptor inhibitors within 2 weeks prior to randomization; or if they received radiation therapy within 4 weeks before randomization, they were excluded from the trial. Patients with known brain metastases or cranial epidural disease were not eligible for enrollment unless adequately treated and clinically stable at least 4 weeks before randomization.

For the trial, participants will be randomized 1:1 to receive either cabozantinib at 40 mg once daily plus atezolizumab at 1200 mg every 3 weeks or a second novel hormonal therapy, either abiraterone at 100 mg once daily and prednisone at 5 mg twice daily or enzalutamide at 160 mg daily, as designated by the investigator prior to randomization.

The co-primary end points of the trial are progression-free survival and overall survival, and key secondary end points include objective response rate (ORR), prostate-specific antigen response rate, and duration of response (DOR).

The design of this trial was informed by the data from the ongoing phase 1b COSMIC-021 trial, in which investigators are examining the novel combination in multiple advanced solid tumors, including non–small cell lung cancer (NSCLC), CRPC, and renal cell carcinoma (RCC).

Results from a cohort of patients with mCRPC from the COSMIC-021 trial were presented during the 2020 ASCO Virtual Scientific Program and showed that the combination induced an ORR of 32%.3 Of 44 patients, 3 achieved complete responses with the treatment and 11 experienced partial responses. Furthermore, 21 patients had stable disease, 8 experienced disease progression, and data were unavailable for 1 patient. Overall, the disease control rate with the combination was 80%.

Moreover, the median time to response was 1.6 months and the median DOR was 8.3 months. Notably, the ORR in a subgroup of 36 patients with high-risk clinical features, such as those with visceral metastases and/or extra-pelvic lymph node metastases, was 33%.

For the trial, the median follow-up was 15.8 months. The majority (77%) of participants patients were white and 4.5% were blackAfrican-American. Half of the patients had an ECOG performance status of 0, while the other half had a status of 1. Eighty-two percent of patients were defined to have high-risk mCRPC; 34% patients had visceral metastases and 61% had extra-pelvic lymph node metastases.

More than half of the patients, or 57%, had a Gleason score of ≥8 at the time of their diagnosis. Twenty-seven percent of patients received previous treatment with docetaxel for metastatic castration-sensitive disease, and all 44 patients received prior treatment with a novel hormonal therapy. The median time between the most recent systemic therapy received and trial enrollment was 1.3 months. Seventy percent of participants received previous radiotherapy and 80% underwent prior surgery for their prostate cancer.

With regard toRegarding safety, the rate of grade 3/4 adverse events (AEs) was 59%. Treatment-related AEs were reported in at least 5% of patients, and included fatigue (7%), diarrhea (7%), and hyponatremia (7%). Immune-related AEs that were grade 3/ or 4 occurred in 4 patients. Nineteen patients experienced AEs that led to dose reductions of cabozantinib. Four patients experienced AEs unrelated to disease progression which led to treatment discontinuation of both agents.

CONTACT-02 is part of a clinical trial collaboration between Exelixis and Roche, which includes 2 other phase 3 trials: CONTACT-01 and CONTACT-03. CONTACT-01, initiated in June 2020, is examining the combination in patients with NSCLC who received prior treatment with an immune checkpoint inhibitor and platinum-containing chemotherapy. CONTACT-03 will examine the novel combination in patients with RCC who received prior treatment with an immune checkpoint inhibitor.

References

Exelixis announces initiation of CONTACT-02 phase 3 pivotal trial of cabozantinib in combination with atezolizumab in previously treated metastatic castration-resistant prostate cancer. News release. Exelixis, Inc. June 30, 2020. Accessed June 30, 2020. bit.ly/2VzDL7D.
Study of cabozantinib in combination with atezolizumab versus second NHT in subjects with mCRPC. ClinicalTrials.gov. Updated June 24, 2020. Accessed June 30, 2020. https://clinicaltrials.gov/ct2/show/NCT04446117.
Agarwal N, Loriot Y, McGregor BA, et al. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results of cohort 6 of the COSMIC-021 study. J Clin Oncol. 2020;38(suppl 15):5564. doi:10.1200/JCO.2020.38.15_suppl.556