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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
  1. Gottfried Konecny1,
  2. Andrea Wahner Hendrickson2,
  3. Boris Winterhoff3,
  4. Cinthiya Chander1,
  5. Sanela Bilic4,
  6. Simon Davenport5,
  7. Adrine Chung6,
  8. Lei-Lani Miller6,
  9. Michael Press5,
  10. Stephen Letrent7 and
  11. Dennis Slamon8
  1. 1UCLA, Obstetrics and Gynecology, Los Angeles, USA
  2. 2Mayo Clinic, 200 First St Sw, Rochester, USA
  3. 3University of Minnesota, Division of Gynecologic Oncology, Minneapolis, USA
  4. 4Vanadro, Pharmacology, Urbandale, USA
  5. 5University of Southern California, Department of Pathology, Los Angeles, USA
  6. 6Translational Research in Oncology-US, Clinical Operations, Los Angeles, USA
  7. 7TORL Biotherapeutics, Clinical Development, Culver City, USA
  8. 8University of California Los Angeles, Department of Medicine, Los Angeles, USA


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.

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