Introduction CLDN6 is highly expressed in multiple cancers with little to no expression in normal tissues, thus is an ideal target to explore a novel therapeutic. TORL-1–23 is first-in-class ADC targeting the tumor-specific antigen CLDN6.

Methods A first in human, 2-part study (TORL123–001 [NCT05103683]) is characterizing the safety, tolerability, pharmacokinetics (PK), maximum tolerated dose (MTD), and antitumor activity of TORL-1–23 monotherapy in participants with ovarian and other advanced solid tumors. Dose escalation (Part 1) implemented an accelerated titration design with up to 6 participants per dose level cohort. Dose expansion (Part 2) will assess participant cohorts with CLDN6-expressing tumors including gynecologic cancers using a CLDN6 IHC companion diagnostic.

Results 19 patients with platinum-resistant/refractory ovarian cancer were evaluated across 8 dose levels (0.2 to 2.4 mg/kg IV every 3 weeks, 21 day cycles) (data cutoff 01APR2023). Most pts had ≥ 3 prior treatment lines in the metastatic setting. The most common treatment-related adverse events were Gr1 peripheral neuropathy (n=3), Gr1/2 fatigue (n=2), and Gr1 nausea (n=2). Dose-limiting toxicities have not been observed. PK data show sustained exposure over the dosing interval. Partial responses (PR) were reported in 6/18 efficacy evaluable participants with CLDN6+ ovarian cancer across all dose levels. 3 of 4 participants with ovarian cancer responded at the 2.4 mg/kg dose level.

Conclusion/Implications In participants with heavily-pretreated CLDN6-expressing ovarian cancer, the novel TORL-1–23 ADC shows a favorable safety/tolerability profile and encouraging antitumor activity. Dose finding is ongoing to identify optimal doses for subsequent development.