Promise of Quavonlimab Plus Pembrolizumab Continues After Extended Follow-Up in Advanced NSCLC

Encouraging anti-tumor activity was observed with the combination of quavonlimab and pembrolizumab (Keytruda) when given as frontline therapy to patients with advanced non–small cell lung cancer (NSCLC) in a phase 1 study (NCT03179436). The combination also had a tolerable safety profile, announced Merck in a press release.

“Updated data from our anti-CTLA-4 antibody quavonlimab in combination with pembrolizumab support the continued development of this new combination and a Phase 3 study of quavonlimab coformulated with pembrolizumab in advanced NSCLC is planned,” stated Vicki Goodman, MD, vice president, oncology clinical research, Merck Research Laboratories.

The first-in-human, open-label, multi-arm study evaluated quavonlimab in combination with pembrolizumab, in which patients received either 25 or 75 mg of the agent every 3 weeks or every 6 weeks in the dose-escalation phase with 100 mg every 3 weeks of pembrolizumab for up to 35 cycles. The primary end point of the study was safety and tolerability, while secondary and exploratory end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).

Overall, the combination had an acceptable safety profile with no unexpected toxicities. Any-grade adverse events (AEs) occurred in 98% of the patients, and treatment-related AEs (TRAEs) occurred in 85%. Grade 3 or higher TRAEs were observed in 36% of the patients in the study, and the most common included increased alanine aminotransferase (8%), pneumonitis (8%), and increased aspartate aminotransferase (6%).

Secondary end points were explored across the 4 cohorts of patients, which included 25 mg of quavonlimab every 6 weeks, 25 mg every 3 weeks, 75 mg every 6 weeks, and 75 mg every 3 weeks. The ORR was 37.5% (95% CI, 22.7-54.2), 40 (95% CI, 24.9-56.7), 27.5 (95% CI, 14.6-43.9), 35.7 (95% CI, 12.8-64.9), respectively. Investigators also evaluated response by PD-L1 status, in which the ORR was 33.3% (95% CI, 16.5-54.0) among those with tumor proportion score (TPS) <1%, 32.1% (95% CI, 19.9-46.3) among those with TPS 1% to 49%, and 50.0% (95% CI, 31.1-68.7) among those with TPS >50%.

Quavonlimab plus pembrolizumab achieved a median PFS was 7.8 months (95% CI, 4.2-14.8), 6.0 (95% CI, 2.0-8.3), 6.0 (95% CI, 3.5-8.1), and 3.4 (1.8-not evaluable [NE]). The median OS, respectively, was 18.1 months (95% CI, 14.2-NE), 18.1 (95% CI, 9.1-21.8), 17.1 (95% CI, 9.0-NE), and 13.7 (95% CI, 3.5-NE), and the median DOR was not reached (NR; 95% CI,4.0-21.6+), 7.9 (95% CI, 2.8-21.4+), 15.9 (95% CI, 3.4-21.4+), and NR (95% CI, 8.8-16.3+).

The safety findings, as well as the efficacy data from this study, support the use of 25 mg quavonlimab every 6 weeks as the recommended phase 2 dose for combination use with pembrolizumab. A phase 3 study is planned to evaluate the combination of quavonlimab plus pembrolizumab in NSCLC.

The purpose of this study was to evaluate the safety and efficacy of the combination in patients with advanced NSCLC after extended follow-up. To be included in this study, patients had to have newly diagnosed stage IIIB/IV NSCLC, and they could not have received prior systemic therapy for advanced stage disease. Patients could not have EGFR mutations or ALK gene rearrangements, nor could they have received neoadjuvant or adjuvant chemotherapy within 6 months of the study drug dosing. Patients of any PD-L1 tumor expression level were allowed on the study, and they had to have measurable disease by RECIST version 1.1 and an ECOG performance status of 0 or 1.

_Reference

_{1. Merck presented three-year survival data for Keytruda (pembrolizumab) in combination with chemotherapy and updated phase 1/2 data for investigational quavonlimab (mk-1308) in combination with Keytruda in advanced non-small cell lung cancer. News Release. Merck. October 16, 2020. Accessed October 19, 2020. https://bit.ly/2T5MDjF​}

_{2. Choi BC, Perets R, Rasco W, et al. Novel anti–ctla4 antibody quavonlimab plus pembrolizumab as first-line therapy for NSCLC: extended follow-up from a phase 1 study. Presented at IASLC 2020 North America Conference on Lung Cancer Worldwide Virtual Event (NACLC 2020); October 16-17. Absract: TS01.02.}