Abstract Background: Second-line options for non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGAs) remain limited and new therapies are urgently needed. Risvutatug rezetecan (Ris-Rez, also known as HS-20093 or GSK5764227) is a promising B7-H3 targeted antibody-drug conjugate with a payload of topoisomerase 1 inhibitor (TOP1i), and the antitumor activity as a monotherapy in NSCLC has been demonstrated in the first-in-human phase 1 study (NCT05276609). This study (NCT06332170) aims to further explore the therapeutic potential of Ris-Rez combinations in solid tumors. Method: This open label phase 1 study enrolled adult patients with advanced solid tumor into 5 cohorts, comprising of dose escalation and dose expansion phase. In cohort 1a, eligible patients received intravenous Ris-Rez at initial dose of 8. 0 mg/kg and adebrelimab at dose of 20 mg/kg every 3 weeks. The preliminary results of efficacy and safety from a subgroup of cohort 1a, involving pretreated patients with non-squamous (nsq) NSCLC without AGAs, are reported here. Results: As of October 20, 2025, 40 patients with nsq-NSCLC without AGAs were enrolled and received ≥1 dose of treatment, with a median age of 64. 0 years (range: 39, 73) and median follow-up time of 8. 7 months (range: 0. 7, 11. 5). All patients received ≥1 line of systemic anti-tumor therapies: platinum-based chemotherapy (100%), immunotherapy (75. 0%) and antiangiogenic therapy (45. 0%). Of 34 efficacy-evaluable patients, the confirmed objective response rate (cORR) was 47. 1% (95% CI: 29. 8, 64. 9) and disease control rate was 94. 1% (95%CI: 80. 3, 99. 3). The 9-month duration of response rate was 90. 0% (95% CI: 47. 3, 98. 5) and median progression-free survival (mPFS) was 11. 2 (95% CI: 11. 2, not reached NR) months. Similar efficacy results were observed in patients who had previously received chemotherapy and immunotherapy but were naive to TOP1i, with a cORR of 52. 2%. Antitumor activity was observed across PD-L1 subgroups: cORR in patients with tumor proportion score (TPS) 1 was 33. 3%, with mPFS of 11. 2 (95% CI: 4. 2, NR) months; and 62. 5% in patients with TPS≥1, with an immature mPFS. Treatment emergent adverse events (TEAEs) leading to dose reduction and discontinuation occurred in 20. 0% and 7. 5% of patients. No TEAEs led to death. Grade ≥3 TEAEs reported in ≥20% patients were white blood cell count decreased (30%), lymphocyte count decreased (30%), neutrophil count decreased (30%) and anaemia (25%). Conclusion: Based on the efficacy of Ris-Rez monotherapy, the combination with adebrelimab showed a trend toward improved efficacy in previously treated patients with nsq-NSCLC without AGAs and no new safety signals were observed. Citation Format: Hua Zhong, Haifeng Liu, Wei Zheng, Linlin Wang, Baogang Liu, Fangling Ning, Yongzhong Luo, Qiming Wang, Weiliang Zhu, Jianying Zhou, Qingwei Zhao, Ruoyu Wang, Xiang Li, Juan Li, Runbo Zhong, Yizhou Jin, Xiangru Mao, Jing Wang, Qingyuan Liu, Xiaoqing Zhang. Combination of risvutatug rezetecan and adebrelimab in previously treated advanced nsq-NSCLC without actionable genomic alterations: Results from ARTEMIS-101, a phase 1 study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT038.
Zhong et al. (Fri,) studied this question.