The efficacy and safety of RC88 in patients with ovarian cancer, non-squamous-non-small-cell lung-carcinoma and cervical cancer: Results from a first-in-human phase 1/2 study.

5551 Background: RC88 is a first-in-class, antibody-drug conjugate (ADC) targeting mesothelin (MSLN) with the payload of Monomethyl auristatin E. MSLN, a glycosylphosphatidylinositol-anchored protein, is overexpressed in several solid tumors with limited expression in normal tissues. RC88-C001 is a single-arm, open-label, multi-center phase 1/2 study evaluating RC88 in patients (pts) with MSLN-expressing advanced solid tumor (NCT04175847). This abstract mainly reports the efficacy results from the dose expansion part (phase 2) of the study. Methods: Pts with MSLN-expressing advanced malignant solid tumors that have failed after standard therapies were enrolled in this study. MSLN was tested by IHC. For phase 2 study, the primary endpoint was ORR by investigator per RECIST v1.1 with secondary endpoints including DCR, PFS, and safety. Results: As of 19 December, 2023, 164 pts with advanced solid tumor were enrolled. Dose escalation phase was completed, and 2.0 mg/kg and 2.5 mg/kg Q3W were expanded in phase 2. In ovarian cancer cohort, 60 pts were enrolled and all with 2+ or 3+ MSLN expression. Forty-two (70%) were FIGO stage IV. Thirty-three (55%) had prior bevacizumab, and 29 (48.3%) had prior PARPi. The number of previous lines of systemic therapy were 2-7. Fifty-four (90%) pts were platinum-resistant. Among the 43 pts with at least one post-baseline tumor assessment, the ORR was 37.2% (16/43). In pts with prior 2-4 lines of therapies, the ORR was 45.5% (10/22) in 2.0 mg/kg and 33.3% (2/6) in 2.5mg/kg. In non-squamous-non-small-cell lung-carcinoma, 26 pts progressed on previous systemic therapy were enrolled and 23 (88.4%) had received ≥ 2 lines of prior therapies. Twenty-three pts had one post-baseline tumor assessment; the ORR was 21.7% (5/23). Among the 15 pts without driver gene mutations, 11 (73%) had received prior platinum-doublet chemotherapy and PD-(L)1 inhibitor. The ORR was 33.3% (5/15) with 1 CR. In cervical cancer, 18 pts progressed on previous systemic therapy were enrolled. In 17 pts with one post-baseline tumor assessment, 11 (64.7%) had received ≥ 2 lines of prior therapies; 12 (70.5%) had prior platinum-doublet chemotherapy and PD-(L)1 inhibitor. The ORR was 35.3% (6/17). TEAEs were reported in 161 pts (98.2%), with 40.2% ≥grade 3 TEAEs. Twenty-three pts (14%) had SAE related to RC88. The most frequent TRAEs were white blood cell count decreased (46.3%), neutrophil count decreased (42.1%), anemia (34.1%), nausea (32.3%), and aspartate aminotransferase increased (31.1%). The overall safety profile was better in 2.0mg/kg than 2.5mg/kg, therefore 2.0mg/kg was chosen as RP2D in further studies in China. Conclusions: RC88 demonstrated tolerable safety and encouraging preliminary efficacy in MSLN-expressing solid tumors, warranting further investigations. Clinical trial information: NCT04175847 .