As reported in JAMA Oncology by Schram et al, the phase IIb tumor-agnostic JAVELIN BRCA/ATM trial has shown that the combination of avelumab and talazoparib did not meet the prespecified objective response rate goal among patients with advanced BRCA1/2-altered or ATM-altered solid tumors. The combination appeared to be more active in a subgroup of patients in the BRCA1/2-altered cohort.
The study enrolled 159 patients into the BRCA1/2 cohort and 41 patients into the ATM cohort from sites in nine countries between July 2018 and April 2020. Patients received avelumab at 800 mg every 2 weeks and talazoparib at 1 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response on blinded independent central review, with the objective of achieving a response rate of 40% in each cohort.
Among the 159 patients in the BRCA1/2 cohort, objective response was observed in 42 (26.4%, 95% confidence interval [CI] = 19.7%–34.0%), including complete response in 9 (5.7%). Median duration of response was 10.9 months (95% CI = 6.2 months to not estimable); responses were ongoing in 17 responders at data cutoff. Among the 41 patients in the ATM cohort, objective response was observed in 2 (4.9%, 95% CI = 0.6%–16.5%).
In the BRCA1/2 cohort, among 119 patients with BRCA1/2-associated tumor types (defined as breast, ovarian, prostate, and pancreatic cancers) vs 40 with non–BRCA1/2-associated cancer types, objective response rates were 30.3% (95% CI = 22.2%–39.3%), including 8 complete responses, vs 15.0% (95% CI = 5.7%–29.8%). The group with non–BRCA1/2-associated tumor types included three patients with uterine leiomyosarcoma; response was observed in all three, with responses ongoing for longer than 24 months. In an exploratory analysis combining the patients with uterine leiomyosarcoma and those with BRCA1/2-associated tumor types into a group defined as BRCA1/2-dependent cancer types, response rates were 32.0% (95% CI = 23.8%–41.0%) in the BRCA1/2-dependent cancer types group vs 8.1% (95% CI = 1.7%–21.9%) in the non–BRCA1/2-dependent cancer types group, with median response durations of 12.5 months (95% CI = 7.4 months to not estimable) vs 5.8 months (95% CI = 5.7 months to not estimable).
Among patients in the BRCA1/2 cohort with available data, objective response was observed in 5 (62.5%) of 8 patients with tumor mutational burden (TMB) ≥ 10 mut/Mb vs 22 (23.9%) of 92 with TMB < 10 mut/Mb.
Grade ≥ 3 treatment-related adverse events occurred in 49.0% of all patients, most commonly anemia (34.0%), thrombocytopenia (15.0%), and neutropenia (11.0%). Treatment-related adverse events led to the discontinuation of any study drug in 11 patients (5.5%). Immune-related adverse events occurred in 25 patients (12.5%) and were grade ≥ 3 in 5 (2.5%). No treatment-related deaths occurred.
The investigators concluded, “In this phase IIb nonrandomized controlled trial, neither the BRCA1/2 nor ATM cohort met the prespecified objective response rate of 40%. Antitumor activity for the combination of avelumab and talazoparib in patients with BRCA1/2 alterations was observed in some patients with BRCA1/2-associated tumor types and uterine leiomyosarcoma; benefit was minimal in non–BRCA-associated cancer types.”
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Pfizer, Merck, and others. For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.