PR062/#686  First-in-human phase 1 study of torl-1–23, a novel claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) in patients with ovarian cancer

• Published in: International journal of gynecological cancer Vol. 33; no. Suppl 4; p. A66
• Main Authors: Konecny, Gottfried, Hendrickson, Andrea Wahner, Winterhoff, Boris, Chander, Cinthiya, Bilic, Sanela, Davenport, Simon, Chung, Adrine, Miller, Lei-Lani, Press, Michael, Letrent, Stephen, Slamon, Dennis
• Format: Journal Article
• Language: English
• Published: Oxford BMJ Publishing Group Ltd 07.11.2023; BMJ Publishing Group LTD
• Subjects: Featured Posters: Poster Rounds with the Professors; Ovarian cancer; Tumors
• ISSN: 1048-891X; 1525-1438
• DOI: 10.1136/ijgc-2023-IGCS.102

IntroductionCLDN6 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.MethodsA 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.Results19 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/ImplicationsIn 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.