A multicenter phase I/II trial of induction chemotherapy followed by camrelizumab, apatinib, plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer

8590 Background: Extensive-stage small-cell lung cancer (ES-SCLC) is a highly aggressive tumor with poor prognosis and limited treatment options. It is necessary to explore new first-line therapeutic strategies to improve patients’ outcomes. This study aimed to assess the safety and efficacy of induction chemotherapy followed by camrelizumab, apatinib plus chemotherapy as first-line treatment in patients with ES-SCLC. Methods: Patients (pts) aged 18-75 years with histopathologically confirmed ES-SCLC and ECOG performance score of 0-1 who did not receive systemic treatment were prospectively enrolled to this study. After two 21-day cycles of induction chemotherapy (etoposide 100 mg/m 2 on days 1-3 and carboplatin AUC 5 mg/mL/min on day 1 [EC]), pts received camrelizumab (200 mg, q3w) plus apatinib (250 mg, qd) and EC for 2-4 cycles, then followed by camrelizumab and apatinib as maintenance treatment until disease progression/unacceptable toxicity/up to two years. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), PFS and OS. Targeted sequencing and whole transcriptome sequencing (WTS) were performed for pts who had sufficient tissue samples. Results: From Jan 28, 2021 to Aug 20, 2022, 40 eligible pts were enrolled. At the data cut-off (Jan 21, 2023), the median follow-up time was 13.6 months. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 72.5% (29/40) of pts. The most common grade 3/4 TRAEs were decreased neutrophil count (35.0%, 14/40), anemia (15.0%, 6/40), decreased platelet count (12.5%, 5/40), increased serum alanine aminotransferase (12.5%, 5/40), and hyponatremia (12.5%, 5/40). Hemoptysis was observed in 15.0% of (6/40) pts, all of whom were grade 1-2. No treatment-related deaths occurred. Efficacy was evaluated in 36 pts who received two cycles of induction therapy and had at least one post-treatment efficacy evaluation. The ORR after two cycles of induction chemotherapy was 66.7% (24/36). The overall ORR and disease control rate reached 88.9% (32/36) and 97.2% (35/36), respectively. The median PFS was 7.4 months (95% CI: 6.5-8.3). The 1-year OS rate was 63.4%. Thirty and 20 pts underwent targeted sequencing and WTS, respectively. Pts with high tumor mutational burden level (TMB ≥ 7.0, p < 0.001), high homologous recombination deficiency score (HRD ≥ 34.0, p = 0.012), and altered RB1 (p < 0.001) presented a longer PFS, respectively. WTS suggested that high expression of cancer-associated fibroblast signature was associated with a shorter PFS (p = 0.001). Conclusions: Induction chemotherapy followed by camrelizumab, apatinib plus EC and then maintenance therapy showed acceptable safety and encouraging efficacy, and might be a promising regimen as first-line treatment in ES-SCLC. TMB, HRD and RB1 might be predictive biomarkers of response to the regimen. Clinical trial information: NCT05001412 .