Efficacy and safety of sintilimab in combination with chemotherapy in previously untreated advanced or metastatic nonsquamous or squamous NSCLC: two cohorts of an open-label, phase 1b study

Abstract

Combining chemotherapy with immunotherapy improves the therapeutic outcome for first-line (1L) patients with advance nonsmall-cell lung cancer (NSCLC). Two cohorts of a phase 1b study (NCT02937116) aimed to evaluate the safety and efficacy of sintilimab, a PD-1 inhibitor, plus chemotherapy in 1L patients with nonsquamous and squamous NSCLC (nsqNSCLC/sqNSCLC); and to identify potential biomarkers for treatment response. Treatment-naïve patients with nsqNSCLC were enrolled and intravenously given sintilimab (200 mg), pemetrexed (500 mg/m2), and cisplatin (75 mg/m2), every 3 weeks (Q3W) for 4 cycles in cohort D. Treatment-naïve patients with sqNSCLC were enrolled and intravenously given sintilimab (200 mg), gemcitabine (1250 mg/m2), and cisplatin (75 mg/m2), Q3W, for 6 cycles in cohort E. The primary objective was to evaluate the safety and efficacy of the treatment. The additional objective was to explore biomarkers for the treatment efficacy. Twenty-one patients with nsqNSCLC, and 20 patients with sqNSCLC were enrolled in cohort D and cohort E, respectively. By the data cutoff (April 17, 2019), 8 (38.1%) patients in cohort D and 17 (85.0%) patients in cohort E experienced grade 3–4 adverse events. The median follow-up duration was 16.4 months (14.8–23.0) in cohort D and 15.9 months (11.7–17.7) in cohort E. The objective response rate was 68.4% (95% CI 43.4%, 87.4%) in cohort D and 64.7% (95% CI 38.3%, 85.8%) in cohort E. Neither PD-L1 expression nor tumor mutation burden value was significantly associated with an improved treatment response. Sintilimab plus chemotherapy exhibited manageable toxicity and an encouraging antitumor activity in patients with nsqNSCLC and sqNSCLC.

Recent updates on Sintilimab in solid tumor immunotherapy

“…Notably, the study revealed that PD-L1 expression, whether tumor proportion score (TPS) ≥ 1% or TPS < 1%, was not correlated with clinical response, and neither did the tumor mutation burden level (TMB). A high TCR Change (TCRC) clonality (> 1) was significantly associated with a better OS, while a low TCRC diversity (< 1) was closely related with a superior PFS [16].…”

Smoking status combined with tumor mutational burden as a prognosis predictor for combination immune checkpoint inhibitor therapy in non‐small cell lung cancer

“…Chen et al found that TMB could not predict treatment efficacy in advanced NSCLC patients treated with camrelizumab combined with apatinib 20 . Another study showed that TMB could not predict the efficacy of sintilimab combined with dual‐drug chemotherapy 21 . In addition, the definition of high TMB measured by different NGS detection platforms (different gene panels) might be different 22 .…”

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

“…The phase 3 trial of sintilimab provided a longer 5.3 months of OS than docetaxel in patients with NSCLC whose disease progressed after chemotherapy ( Yang et al, 2020 ). Besides of monotherapy, sintilimab combined with either chemotherapy or anlotinib as the first-line treatment demonstrated encouraging antitumor activities ( Chu et al, 2021 ; Jiang et al, 2021 ) and combined with anlotinib, it showed a longer PFS of 15 months representing a novel chemotherapy-free regimen of NSCLC ( Zhang et al, 2021 ). The addition of sintilimab to chemotherapy also revealed promising efficacy and manageable safety in untreated gastric/gastroesophageal junction (GEJ) adenocarcinoma ( Jiang et al, 2020 ).…”