Abstract CT037: A first-in-human phase 1 trial of a novel claudin 6 (CLDN6)-targeting antibody drug conjugate (ADC) QLS5132 in patients (pts) with platinum-resistant ovarian cancer (PROC)

Abstract Background: QLS5132 is a highly selective ADC composed of a humanized anti-CLDN6 hIgG1 antibody and a novel topoisomerase-1 inhibitor as cytotoxic payload via a hydrophilic cleavable linker LK1b, with a drug-to-antibody ratio of 8. QLS5132 showed an expanded therapeutic window and potent antitumor activity in PROC in preclinical studies. Methods: The trial (NCT06932094) recruited pts with histologically or cytologically confirmed advanced PROC, who failed or had no standard therapy. Accelerated titration design and Bayesian optimal interval design were adopted in dose-escalation stage. QLS5132 was administered via intravenous infusion once Q3W at dose levels of 1. 6 mg/kg, 3. 2 mg/kg, 4. 8 mg/kg, 5. 6 mg/kg, and 6. 4 mg/kg. Two dose levels would be selected in dose-expansion phase. The primary endpoints were safety. Results: As of Jan 21, 2026, 28 pts with advanced PROC were enrolled (ovarian cancers: 26 pts, fallopian tube cancers: 2 pts). The dose-escalation for the 6. 4 mg/kg cohort was completed. Median age was 57. 5 years. Ten (35. 7%) pts received ≥5 lines of prior treatment, 25 (89. 3%) pts received prior bevacizumab, and 22 (78. 6%) pts received prior polyADP ribose polymerase inhibitors. Dose-limiting toxicity of grade 4 platelet count decreased occurred in one patient at 6. 4 mg/kg dose level. Twenty-six (92. 9%) pts experienced TEAEs (treatment-related, 92. 9%). The most common TRAEs of any grade with incidence 50% were nausea (85. 7%), anorexia (60. 7%), anemia (53. 6%), and weakness (53. 6%). Alopecia, bone pain, back pain, hypoesthesia, and mucositis oral occurred in one (3. 6%) patient, respectively. No interstitial lung disease, ocular toxicity, or febrile neutropenia occurred. Most gastrointestinal TRAEs were grade 1 or 2. Nine (32. 1%) pts experienced grade ≥3 TRAEs. The hematological TRAEs of grade ≥3 occurred in 2 (66. 7%) pts at 6. 4 mg/kg dose level, and 5 (20. 0%) pts at 6. 4 mg/kg dose level. TRSAEs occurred in one (3. 6%) patient at 6. 4 mg/kg dose level, which were hematologic toxicities. There were no TRAEs leading to treatment discontinuation or death. Nine pts achieved PR (2 in 3. 2 mg/kg, 5 in 4. 8 mg/kg, and 2 in 6. 4 mg/kg dose level), including 2 pts with undetected CLDN6 expression. In 18 efficacy-evaluable pts across all dose levels, the ORR and DCR were 50. 0% and 94. 4%, respectively. In 17 efficacy-evaluable pts at ≥3. 2 mg/kg dose levels, the ORR and DCR were 52. 9% and 100%, respectively. QLS5132 showed response regardless of baseline CLDN6 expression. After multiple administrations, the CA125 levels in most pts showed a decreasing trend compared with baseline. Conclusions: QLS5132 was well-tolerated under potential recommended dose levels (6. 4 mg/kg) and presented remarkable antitumor activity in pts with advanced PROC. Patients enrollment for PROC, non-small cell lung cancer, gastric cancer, and other cancers are ongoing. Citation Format: Yang Xiang, Zhengbo Song, Juan Li, Liang Chen, Yang Sun, Dongling Zou, Yongsheng Li, Songling Zhang, Yanhua Ding, Yu Gu, Xin Liu, Tao Zhang, Xiaoyan Kang, Weikang Tao, Tao Zhu. A first-in-human phase 1 trial of a novel claudin 6 (CLDN6) -targeting antibody drug conjugate (ADC) QLS5132 in patients (pts) with platinum-resistant ovarian cancer (PROC) 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 CT037.