Dr Johnson on Domvanalimab, Zimberelimab, and Etrumadenant in NSCLC

Melissa L. Johnson, MD, director, Lung Cancer Research, Sarah Cannon Research Institute; chair, Oncology Department, member, Medical Executive Committee, TriStar Centennial Medical Center, discusses findings from the phase 2 ARC-7 trial (NCT04262856) in patients with previously untreated metastatic, PD-L1–high non–small cell lung cancer (NSCLC).

ARC-7 included patients with previously untreated stage IV NSCLC and a PD-L1 score of at least 50% who were randomized 1:1:1 to receive monotherapy with the PD-1 inhibitor zimberelimab (AB122; arm 1), a doublet with the TIGIT inhibitor domvanalimab (AB154) plus zimberelimab (arm 2), or a triplet with the A2R antagonist etrumadenant (AB928) plus domvanalimab and zimberelimab (arm 3). A presentation of the data during an ASCO plenary series in December 2022 showed that patients in the domvanalimab-containing arms achieved clinically meaningful objective response rate (ORR) and progression-free survival (PFS) improvements vs those who received zimberelimab alone.

At an updated analysis of this trial that was presented at the 2023 ASCO Annual Meeting, the ORRs were 30%, 40%, and 44% in arms 1, 2, and 3, respectively. In addition, the median PFS was 5.4 months, 9.3 months, and 9.9 months in arms 1, 2, and 3, respectively. The median duration of response was 13.2 months, not reached, and 23.7 months in arms 1, 2, and 3, respectively, and the overall survival data remain immature.

Regarding safety, 100%, 98%, and 98% of patients in arms 1, 2, and 3, respectively, experienced treatment-emergent adverse effects (TEAEs) of any grade, and 64%, 46%, and 60%, respectively, experienced TEAEs of grade 3 or higher. The most common TEAEs of any grade were nausea, fatigue, constipation, dyspnea, pneumonia, decreased appetite, and diarrhea. The most common TEAEs of grade 3 or higher were pneumonia and anemia.

Importantly, the ARC-7 data have remained consistent between the initial presentation of the data in December 2022 and the presentation of the updated analysis in June 2023, Johnson says. The addition of domvanalimab to the PD-1 inhibitor zimberelimab improves clinical outcomes in patients with treatment-naïve, PD-L1–high, metastatic NSCLC, Johnson emphasizes. These findings led to the initiation of the ongoing pivotal phase 3 ARC-10 trial (NCT04736173), which is comparing domvanalimab plus zimberelimab vs pembrolizumab (Keytruda) in this population, Johnson concludes.