Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial

Abstract

Background Sintilimab blocks the interaction between programmed death-1 (PD-1) and its ligands. The safety and efficacy of sintilimab combined with oxaliplatin/capecitabine (CapeOx) as first-line treatment were evaluated in patients with gastric (G)/gastroesophageal junction (GEJ) adenocarcinoma in a phase Ib clinical trial. Methods Patients with locally advanced or metastatic G/GEJ adenocarcinoma without previous systemic treatment were enrolled as one cohort of a multi-cohort study. Sintilimab was administered at a dose of 200 mg intravenously (IV) in combination with CapeOx (1000 mg/m 2 capecitabine orally, bid, D1–14 and 130 mg/m 2 oxaliplatin IV, D1) every 21 days for up to 6 cycles. After combination treatment, patients continued to receive sintilimab (200 mg) at 3 weekly intervals as maintenance therapy until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent, or for up to 24 months. Adverse events (AEs) were monitored to assess safety in terms of their frequency, intensity and causality. The efficacy endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Tumor mutation burden (TMB) was evaluated for its association with clinical response. Results A total of 20 patients were enrolled and received sintilimab plus CapeOx. All patients reported treatment-related AEs (TRAEs). Grade 3–4 TRAEs were found in 11 (55.0%) patients. Seventeen patients obtained partial response and the ORR was 85.0% (95% CI: 62.1–96.8%). Three (15.0%) had stable disease and DCR was 100.0% (95% CI: 83.2–100.0%). As data cutoff of May 1, 2019, the median follow-up was 7.8 months. The median PFS was 7.5 months (95% CI: 6.2–9.4) and median OS had not been reached. The OS rates at 6 months and 12 months were 100.0 and 68.0%. No association was observed between TMB and efficacy. Conclusions Sintilimab combined with CapeOx as first-line treatment demonstrated acceptable safety and promising efficacy. Trial registration ClinicalTrials.gov, NCT02937116 . Registered 8 October 2016.

Sintilimab: A Promising Anti-Tumor PD-1 Antibody

“…In a phase I study NCT02937116, 20 gastric/gastroesophageal junction adenocarcinoma (G/GEJ) patients were enrolled; among them, 200 mg sintilimab was administered intravenously in combination with CapeOx (1,000 mg/m 2 capecitabine orally, bid, days 1-14 and 130 mg/m 2 oxaliplatin intravenously, day 1) every 21 days for up to six cycles; after combination treatment, patients continued to receive sintilimab (200 mg) at 3 weekly intervals as maintenance therapy until progressive disease, unacceptable toxicity, withdrawal of informed consent, or for up to 24 months (53). The combination therapy resulted in PFS of 7.5 months, an ORR of 85% and a DCR of 100% (53). In comparison, nivolumab in combination with CapeOx until disease progression, unacceptable toxicity, or consent withdrawal resulted in PFS, ORR, DCR of 10.6 months, 76.5% (13/17) and 88.2% (15/17) in such patients (54).…”

Recent updates on Sintilimab in solid tumor immunotherapy

“…The OS rates for 6 months and 12 months were 100.0% and 68.0% respectively, suggesting a significant anti-tumor effect and benign tolerability. Interestingly, TMB was not associated with curative effects in the trial [ 25 ]. ATTRACTION-4 was a clinical trial of nivolumab combined with SOX/CapeOX among patients with advanced G/GEJ cancer as the first-line therapy.…”

“…Common sintilimab-associated irAEs are characterized by pyrexia, hypothyroidism, rash, pneumonitis, fatigue and decreased platelet count [ 6 , 12 , 25 ]. Infrequent irAEs symptoms include PNSs [ 21 ], immune induced-myositis/myocarditis and rhabdomyolysis [ 37 ], high-CPK asymptomatic hypothyroid myopathy [ 38 ], cardiac toxicity [ 18 ], and adrenal insufficiency [ 30 ].…”

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

“…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 ).…”