TORL Bio Presents Promising Phase 1 Data for CLDN6-Targeted ADC TORL-1-23 in Advanced Cancers
Key Insights
TORL-1-23 demonstrates clinically meaningful and durable responses in patients with Claudin 6 (search) positive platinum-resistant ovarian cancer (search), with a manageable safety profile.
The Phase 1 study included patients with ovarian, non-small cell lung cancer (search), and other CLDN6+ cancers, with expansion cohorts currently under investigation.
Data supports the initiation of a registration-enabling Phase 2 study in patients with CLDN6+ platinum-resistant ovarian cancer (search), addressing a significant unmet need.
TORL BioTherapeutics (search) presented updated Phase 1 results for TORL-1-23, a Claudin 6 (search) (CLDN6) targeted antibody-drug conjugate (ADC), at the 2024 European Society of Medical Oncology Congress (ESMO) in Barcelona, Spain. The data from the TORL123-001 (TRIO-049) trial, presented by Gottfried E. Konecny, M.D. of UCLA Medical Center, showed encouraging antitumor activity and a manageable safety profile in patients with advanced cancers.
The ongoing Phase 1 study enrolled 81 patients with CLDN6+ ovarian, testicular (search), endometrial (search), non-small cell lung cancer (search) (NSCLC (search)), and other cancers. These patients, heavily pretreated with an average of 4 prior therapeutic regimens, were evaluated for safety and efficacy across 11 dose cohorts (0.2 mg/kg to 4.0 mg/kg) administered intravenously every 3 weeks.
Key Findings from the Phase 1 Study
TORL-1-23 was generally well-tolerated at doses ranging from 0.2 mg/kg to 2.4 mg/kg every 3 weeks. The most common adverse events were grade 1 or 2 fatigue, peripheral neuropathy, and alopecia. The most frequent grade 3+ adverse event was neutropenia (search). Notably, febrile neutropenia, interstitial lung disease, and ocular toxicities were not observed at these doses.
To mitigate neutropenia (search), prophylactic pegfilgrastim was implemented at doses of 3.0 mg/kg or higher, proving effective in reducing the incidence of this adverse event. The maximum tolerated dose (MTD) has not yet been identified, and dose escalation is ongoing.
Encouraging antitumor activity was observed across all enrolled cancer histologies and dose levels in this heavily pretreated population. Specifically, at doses of 2.4 mg/kg and 3.0 mg/kg every 3 weeks, deep and durable confirmed responses were seen in 9 out of 20 (45%) patients with CLDN6+ platinum-resistant/refractory ovarian cancer (search) (PROC). The median duration of response exceeded 6 months at both dose levels.
Clinical Significance and Future Directions
According to Dennis Slamon, MD, PhD, Professor of Medicine and Chief of the Division of Hematology/Oncology at UCLA’s David Geffen School of Medicine, the emerging Phase 1 profile of TORL-1-23 suggests that this ADC may achieve the objective of molecularly targeted therapeutics in cancer: to significantly enhance efficacy while maintaining or improving safety over established treatments, particularly for patients with platinum-resistant ovarian cancer (search), where there is a serious unmet medical need.
Phase 1 evaluation of TORL-1-23 in NSCLC (search) and other CLDN6+ cancers is ongoing. TORL BioTherapeutics (search) is initiating a multi-dose Phase 2 study designed to support accelerated registration in CLDN6+ PROC.
About Claudin 6
Claudin 6 (search) (CLDN6) is a tumor-specific transmembrane protein overexpressed in multiple cancers, including ovarian, non-small cell lung, endometrial (search), and testicular (search) cancers, with limited expression in normal tissues. Its overexpression is implicated in cancer initiation, progression, and metastasis, and correlates with shortened survival outcomes in ovarian cancer (search) patients, making it an ideal target for antibody-drug conjugate development.