Nivolumab plus Trastuzumab with S-1/Capecitabine plus Oxaliplatin for HER2-Positive Advanced Gastric Cancer: The Ni-HIGH Study
Based on evidence of additive antitumor effect with the addition of an anti–programmed death (PD)-1 antibody to trastuzumab, the open-label, nonrandomized phase 1b Ni-HIGH study investigated the safety and tolerability of nivolumab plus trastuzumab combined with S-1 or capecitabine and oxaliplatin for chemotherapy-naïve patients with HER2-positive advanced gastric cancer. Safety and early efficacy results (during 8 cycles; 6 months) of this study were reported at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
This 2-part study included a safety part (n = 12), followed by expansion to assess efficacy (n = 30). The study enrolled chemotherapy-naïve adult patients (≥20 years of age) with histologically confirmed HER2-positive advanced gastric cancer with measurable lesions that received treatment at 4 Japanese centers between November 2018 and January 2021. Eligible patients received nivolumab (360 mg, day 1) and trastuzumab (cycle 1: 8 mg/kg; cycle 2 onward: 6 mg/kg, day 1), oxaliplatin (130 mg/m2, day 1) in combination with either S-1 (40 mg/m2 twice daily, days 1-14; cohort 1) or capecitabine (1000 mg/m2 twice daily, days 1-14; cohort 2) every 3 weeks until disease progression or unacceptable toxicity. Data cutoff date was July 31, 2021.
A total of 42 patients with HER2-positive advanced gastric cancer were enrolled; of these, 21 patients received nivolumab plus trastuzumab in combination with S-1 plus oxaliplatin (SOX), and 21 patients received nivolumab plus trastuzumab in combination with oxaliplatin plus capecitabine (CapeOx). At data cutoff, 34 patients discontinued protocol treatment, 26 due to progressive disease, and 3 (10.3%) due to an adverse event (AE). Grade ≥3 AEs occurred in 25 (59.5%) patients, including neutropenia in 8 patients (19.0%) and diarrhea in 4 patients (9.5%). Immune-related grade ≥3 AEs occurred in 7 (16.6%) patients, including diarrhea/colitis in 4 (9.5%) patients and endocrine-related AEs in 2 (4.8%) patients.
Overall (both SOX and CapeOx cohorts), an overall response rate (ORR) of 76.2% was achieved, including 2 complete responses (CRs; 4.8%) and 30 partial responses (PRs; 71.4%); the disease control rate (DCR) was 97.6%. Conversion surgery was performed in 2 (4.8%) patients. Median progression-free survival (PFS) was 10.8 months; the 6-month PFS rate was 68.7%. In the SOX cohort, an ORR of 71.4% was achieved, including 1 CR (4.8%) and 14 PRs (66.7%); DCR was 95.2%, median PFS was 8.4 months, and the 6-month PFS rate was 52.4%. In the CapeOX cohort, an ORR of 81.0% was achieved, including 1 CR (4.8%) and 16 PRs (76.2%); DCR was 100%, median PFS was 16.3 months, and the 6-month PFS rate was 85.7%. Median overall survival was not reached in the overall cohort and the CapeOx cohort; median overall survival was 14.0 months in the SOX cohort.
Based on early efficacy results of the Ni-HIGH study, it was concluded that nivolumab plus trastuzumab and either S-1 or capecitabine plus oxaliplatin was tolerable and showed promising antitumor activity in chemotherapy-naïve patients with HER2-positive advanced gastric cancer.
Takahari D, Shoji H, Minashi K, et al. Safety and early efficacy results of a phase Ib study of nivolumab plus trastuzumab with S-1/capecitabine plus oxaliplatin for HER2-positive advanced gastric cancer (Ni-HIGH study). Presented at: 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, January 20-22, 2022. Abstract 276.
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