Safety and efficacy of QL1706 plus carboplatin/etoposide (EC) as first-line (1L) treatment for extensive-stage small-cell lung cancer (ES-SCLC): The results from a phase II single-arm study.

8525 Background: Although the combination of PD-L1 inhibitor and platinum-etoposide chemotherapy has been the preferred 1L treatment for patients (pts) with ES-SCLC, the clinical benefit of the addition of PD-L1 inhibitor was still modest. QL1706 is a novel bifunctional antibody, containing a mixture of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 antibodies produced by MabPair. In phase I trials, QL1706 monotherapy has shown promising antitumor efficacy in nasopharynx cancer and cervical cancer, as well as other advanced solid tumors including SCLC (to be published). This study aims to assess the safety and efficacy of QL1706 plus EC in treatment-naïve ES-SCLC. Methods: In this phase II, open-label, single-arm, multi-center study, eligible pts (18-75 years, ECOG 0-1) received 4-6 cycles of QL1706 (5mg/kg, IV, Q3W) plus EC (etoposide, 100 mg/m 2 , D1-3, Q3W; carboplatin, AUC = 5, D1, Q3W), followed by the maintenance therapy of QL1706 until disease progression, intolerable toxicity or other discontinuation events defined in the study protocol. Tumor imaging was performed every 6 weeks for the first year and every 9 weeks thereafter. The primary endpoint is safety. Results: From Apr 18, 2022 to Jul 27, 2022, a total of 40 pts were enrolled with a median age of 58.5 years (range, 38−73). 87.5% pts were men, 80% were smokers and 90% had ECOG PS of 1. As of data cutoff (Jan 16, 2023), the median QL1706-treatment duration was 5.9 (range, 0.7−8.9) mo. Twenty pts remained on treatment and 20 pts discontinued due to progressive disease (16, 40.0%) or patient decision (4, 10.0%). Thirty two (80.0%) pts had at least one TRAE (QL1706-related). Fifteen (37.5%) pts experienced grade 3-4 TRAEs, including neutropenia (8, 20%), thrombocytopenia (4, 10%), anemia (3, 7.5%), WBC count decreased (2, 5.0%), AST increased (2, 5.0%), ALT increased (1, 2.5%), gamma-GT increased (1, 2.5%), rash (1, 2.5%), and diarrhea (1, 2.5%). No grade 5 TRAE occurred. No AE led to discontinuation of any treatment. Of the 39 pts who had at least 1 post-baseline tumor assessment, 37 achieved PR (35 confirmed and 2 unconfirmed) and 1 achieved SD. Thus, the confirmed ORR was 89.7% (95% CI, 75.8%−97.1%), and the DCR was 97.4% (95% CI, 86.5−99.9%) (per RECIST v1.1). The mDoR was 4.5 (95% CI, 4.2−not evaluable) mo, with the longest response duration more than 7.2 mo and ongoing. The mPFS was 5.7 (95% CI, 5.4−7.1) mo, together with 3 mo- and 6 mo-PFS rates of 94.8 (95% CI, 80.8−98.7%) and 44.7% (95% CI, 27.3−60.6%), respectively. With a median follow-up time for OS of 6.2 mo, the mOS has not been reached. Conclusions: QL1706 plus EC chemotherapy showed tolerable safety profile and promising efficacy as first-line treatment for pts with ES-SCLC. These data support further clinical development of QL1706 in ES-SCLC. Clinical trial information: NCT05309629 .