Initial results of dose finding in a first-in-human phase 1 study of a novel Claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 in patients with advanced solid tumors.

• DOI: 10.1200/jco.2023.41.16_suppl.3082
• Publication Date: 2023-06-04T15:23:35Z
• Authors: Gottfried E. Konecny; Andrea Elisabeth ...; Boris Winterhoff; Cinthiya Chander; Sanela Bilic; Simon Davenport; Adrine Chung; Lei-Lani Miller; Michael F. Press; Stephen P. Letrent; Dennis J. Slamon
• Keywords: Tolerability

3082 Background: CLDN6, a member of the claudin family tight junction proteins, is expressed at high levels in multiple human malignancies and has little to no expression normal tissues. This profile makes CLDN6 an ideal target for development new therapeutics. TORL-1-23 first-in-class ADC targeting tumor-specific antigen CLDN6. Methods: TORL123-001 (NCT05103683) ongoing, 2-part, first study characterize safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase 2 (RP2D) monotherapy participants with advanced solid tumors. Serum pharmacokinetics (PK), immunogenicity clinical efficacy are also assessed. administered as 30-minute IV infusion once every 3 weeks 21-day cycles. During Part 1 (Dose Escalation), cohorts 6 evaluated each level according accelerated titration design. In Expansion), several patients CLDN6-expressing cancers will be confirm RP2D ovarian cancer, NSCLC, other using IHC companion diagnostic. Results: As 01FEB2023, 22 (n=18), testicular (n=3), endometrial (n=1) were enrolled treated across 8 ranging from 0.2 2.4 mg/kg weeks. 95% pts had received ≥ prior lines treatment metastatic setting. The most common treatment-related adverse events Gr1/2 fatigue (n=5), Gr1 peripheral neuropathy (n=4), nausea (n=3). No DLTs have been reported reductions required. Preliminary PK data demonstrate sustained exposure over 21 day dosing interval low serum MMAE indicating off-target outside tumor. Partial responses (PR) observed 4/17 evaluable CLDN6+ disease (3 ovarian, testicular). Dose escalation ongoing updated results presented. Conclusions: favorable safety/tolerability characteristics preliminary antitumor activity heavily-pretreated cancers. Doses above historic MTD containing ADCs may explored given up mg/kg. finding identify optimal doses subsequent development. Clinical trial information: NCT05103683 .