Phase 2 Study Results Suggest Similar Efficacy, Safety of Sintilimab Vs Pembrolizumab in Advanced NSCLC

Sintilimab elicited comparable efficacy and safety vs pembrolizumab (Keytruda), regardless of their use as monotherapy or in combination with chemotherapy, for use in patients with untreated metastatic non–small cell lung cancer, according to a phase 2 randomized trial presented at the 2022 World Conference on Lung Cancer.

Amongst all patients treated with sintilimab alone or combined with chemotherapy, the objective response rate (ORR) was 52.9% (95% CI, 35.1%-70.2%) vs 32.4% (95% CI, 17.4%-50.5%) with pembrolizumab regimens (P = .14). ORRs by individual treatment arm were 46.2% (95% CI, 19.2%-74.9%) with sintilimab monotherapy (arm A; n = 13), 35.7% (95% CI, 12.8%-64.9%) for pembrolizumab monotherapy (arm B; n = 14), 57.1% (95% CI, 34.0%-78.2%) for sintilimab in combination with chemotherapy (arm C; n = 21), and 30.0% (95% CI, 11.9%-54.3%) for pembrolizumab plus chemotherapy (arm D; n = 20). Based on previous trials assessing the efficacy of pembrolizumab, the estimated ORR threshold of 40% was met in the experimental arm.

Patients were randomized 1:1 to receive either PD-1 inhibitor and were further stratified by pathologic subtype and brain metastases. Those with a tumor proportion score of 50% or more received the agent alone and the remainder were administered immunotherapy plus chemotherapy. Both agents were administered at 200 mg every 3 weeks until disease progression, intolerability, or 24 months of therapy; chemotherapy was administered for 4 cycles in those who qualified. The primary end point was ORR with secondary end points of duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Between all arms, patients had comparable baseline characteristics.

Comparing all patients treated with sintilimab and pembrolizumab, the DCRs were 88.2% (95% CI, 72.6%) vs 97.1% (95% CI, 84.7%-99.9%), respectively (P = .036). Breaking that down by individual treatment arms, sintilimab monotherapy arm yielded a DCR of 84.6% (95% CI, 54.6%-98.1%), 100% (95% CI, 76.8%-100%) for pembrolizumab monotherapy, 90.5% (95% CI, 69.6%-98.8%) with the sintilimab combination, and 95.0% (95% CI, 75.1%-99.8%) with the pembrolizumab combination. The median DOR was 11.2 months in the sintilimab treatment arms and was not reached (NR) with pembrolizumab (P = .22).

“[When assessing the changes in target lesions with] monotherapy, outcomes were comparable in the sintilimab and pembrolizumab arms. When patients had a higher PD-L1 expression, they had a better response rate. With the combination therapy, sintilimab plus chemotherapy showed a better [response] than the pembrolizumab plus chemotherapy arm,” Si-Yang Maggie Liu, MD,a fellow in the Department of Hematology in the First Affiliated Hospital at Jinan University in China, said during the presentation.

Median PFS was 8.0 months (95% CI, 4.2-14.0) in arms A and C vs 7.5 months (95% CI, 5.8-NR) in arms B and D, with 12-month rates of 32.5% vs 40.9%, respectively. The median PFS in arm A was 8.4 months (95% CI, 2.8-8.4), 7.5 months (95% CI, 4.1-NR) in arm B, 7.0 months (95% CI, 4.0-14.0) in arm C, and 7.2 months (95% CI, 5.6-NR) in arm D. At 12 months, the PFS rate was not estimable in the sintilimab monotherapy arm, 46.4% in arm B, 33.7% in arm C, and 37.0% in arm D.

Median OS was NR months (95% CI, 9.1-NR) in arms A and C vs 17.5 months (95% CI, 10.7-22.9) in arms B and D, with 12-month rates of 63.6% vs 68.2%, respectively. The median OS was not reached in arm A, 10.7 months (95% CI, 7.5-22.9) in arm B, 15.1 months (95% CI, 8.8-NR) in arm C, and 17.5 months (95% CI, 12.5-NR) in arm D. At 12 months, the OS rates by individual treatment arm were 75.2% (95% CI, 50.6%-99.8%), 49.9% (95% CI, 20.5%-79.3%), 59.4% 995% CI, 37.1%-81.7%), and 80.7% (95% CI, 63.7%-97.8%), respectively.

With a median follow-up of 11.5 months, the median duration of treatment was 7.3 months in the sintilimab monotherapy arm, 7.7 months in the pembrolizumab monotherapy arm, 7.4 months in the sintilimab combination arm, and 6.3 months in the pembrolizumab monotherapy arm.

Any-grade adverse effects (AEs) occurred in 92.3% of patients in arm A, 92.9% in arm B, 100% in arm C, and 90.9% in arm D. In terms of safety, grade 3/4 AEs occurred in 46.2%, 42.9%, 77.3%, and 59.1% of patients, with serious AEs occurring in 61.5%, 50.0%, 45.5%, and 40.9%, respectively. Treatment-related AEs (TRAEs) that leading to death occurred in 7.7%, 14.3%, 18.2%, and 9.1% of patients; with TRAEs leading to discontinuation in 7.7%, 21.4%, 13.6%, and 9.1%; and TRAEs leading to treatment withdrawal in 0.0%, 7.1%, 4.5%, and 9.1%, respectively.

Reference

Liu SYM, Zhou Q, Yan HH, et al. Sintilimab versus pembrolizumab in monotherapy or combination with chemotherapy as first-line therapy for advanced non–small cell lung cancer-results from phase 2 randomized clinical trial (CTONG1901). Presented at the 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract WS08.09.