SMET12 and toripalimab combined chemotherapy in patients with advanced non-small cell lung cancer who are treatment-naive or have developed resistance to standard therapy.

Abstract

8570 Background: SMET12 is a recombinant anti-EGFR and CD3 bispecific antibody independently developed by Zhejiang Shimai Pharmaceutical. This study aims to evaluate the efficacy and safety of SMET12 in combination with toripalimab and chemotherapy in treatment-naïve, post-first-line immune checkpoint inhibitor-resistant, and EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) patients who are resistant to TKI treatment. Methods: This is a single-arm, cohort clinical study involving three cohorts. The primary inclusion criteria are histologically confirmed EGFR protein-expressing metastatic NSCLC patients, specifically divided into: (1) Cohort A: treatment-naïve subjects; (2) Cohort B: subjects resistant to first-line immune checkpoint inhibitor therapy; (3) Cohort C: EGFR mutation-positive subjects resistant to TKI treatment. All subjects will receive a combination regimen of SMET12, toripalimab, and chemotherapy after entering the treatment phase, with the chemotherapy cycle being 2-4 cycles. After chemotherapy, subjects with stable or effective results will enter the maintenance therapy phase with SMET12 and toripalimab until disease progression or unacceptable toxicity occurs. The treatment regimen is as follows:SMET12 30μg Q2W + toripalimab 3mg/kg Q2W+ chemotherapy Q3W. Specific chemotherapy regimens are: Cohort A: pemetrexed + carboplatin Q3W for lung adenocarcinoma; nab-paclitaxel + cisplatin Q3W for lung squamous cell carcinoma; Cohort B: docetaxel Q3W; Cohort C: pemetrexed + carboplatin Q3W. The primary endpoints are safety and efficacy indicators, including objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS). Results: From March 7, 2024, to January 21, 2025, a total of 31 patients participated in this study, of which 27 patients were evaluable for efficacy. The results showed: the ORR for Cohort A was 83.3%, DCR was 100%, and the median PFS was 8.3 months (95%CI: 3.79, 12.8); the ORR for Cohort B was 22.2%, DCR was 66.7%, and the median PFS was 4.2 months (95%CI: 3.62, 4.78); the ORR for Cohort C was 41.7%, DCR was 100%, and the median PFS was 7.2 months (95%CI: 5.0, 9.4).Grade ≥3 treatment-related adverse events included leukopenia (19.4%), pneumonia (16.1%), immune-related pneumonitis (13.0%), immune-related hepatitis (3.2%), immune-related myositis (3.2%), and anemia (3.2%). Conclusions: SMET12 in combination with toripalimab and chemotherapy shows good tolerability and efficacy in treatment-naïve, post-immune therapy-resistant EGFR protein-expressing, and post-TKI treatment-resistant EGFR mutation-positive advanced NSCLC patients. Clinical trial information: NCT06208033 .