A Phase I, First in Human, Dose-Escalation Study of TORL-1-23 in Participants With Advanced Cancer

Study Identifier:
TORL123-001
CT.gov Identifier:
NCT05103683
EudraCT Identifier:
202451718940
EU Trial (CTIS) Number:
2024-517189-40-00
Study Contact Information:
N/A
Recruiting

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Study Summary

To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-1-23 in patients with advanced cancer

Study Objectives

To characterize the safety, tolerability, and DLT and determine the MTD and RP2D for TORL-1-23

To characterize the PK of TORL-1-23 and its breakdown products (MMAE and TORL-1-23 MAB)

To assess the preliminary antitumor activity of TORL-1-23 in participants with advanced cancer

To assess the immunogenicity of TORL-1-23

To characterizes the safety, tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of TORL-1-23 in participants with advanced solid tumors.

Pharmacokinetics (PK), immunogenicity and clinical efficacy are also assessed.

In Dose Escalation, cohorts up to 6 participants are evaluated at each dose level according to an accelerated titration design. In Dose Expansion, patients with CLDN6-expressing cancers will be evaluated to confirm the RP2D in ovarian cancer, NSCLC, and other CLDN6+ cancers using an IHC companion diagnostic. Doses above the historic MTD for MMAE containing ADCs are being evaluated given the favorable safety/tolerability at doses <2.4 mg/kg.

To 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 expansion (Part 2) will assess participant cohorts with CLDN6-expressing tumors including gynecologic cancers using a CLDN6 IHC companion diagnostic.

Part 2, expansion, of TORL's phase 1 study to assess the safety, pharmacokinetics, biomarkers, and antitumor activity of TORL-1-23.

Study objectives include evaluation of safety, tolerability, DLTs, RP2D, antitumor activity, and correlation of CLDN6 levels with response

Part 2: Pts with CLDN6-expressing cancers will be evaluated to confirm the RP2D in ovarian cancer, NSCLC, and other cancers using a CLDN6 IHC companion diagnostic.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Ovarian
Solid Tumor
Endometrial
Testicular
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: Monotherapy Dose Finding - Part 1 TORL-1-23 Drug: TORL-1-23 antibody drug conjugate (ADC) Experimental: Expansion as Monotherapy - Part 2 TORL-1-23 Drug: TORL-1-23 antibody drug conjugate (ADC) Patients received TORL-1-23 from 0.2 to 2.4 mg/kg IV every 21 days ASCO 2023: TORL-1-23 given IV every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal. Intrapatient dose escalation allowed Patients were administered IV every 3 weeks. Dose escalation (Part 1) implemented an accelerated titration design with up to 6 participants per dose level cohort. 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) TORL-1-23 is administered as a 30-min IV infusion Q3W. IGCS 2024: Part 1: subjects received escalating doses of TORL-1-23 across 10 dose levels (0.2 to 4.0 mg/kg).
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Advanced solid tumor
  • Measurable disease, per RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate organ function
Exclusion criteria
  • Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade < or =1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements
  • Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of TORL-1-23
  • Progressive or symptomatic brain metastases
  • Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection
  • History of significant cardiac disease
  • History of myelodysplastic syndrome (MDS) or AML
  • History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded
  • If female, is pregnant or breastfeeding

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Dublin
Dublin, Ireland, D07 R2WY
Investigator
Austin Duffy
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer
Ovarian
Solid Tumor
Endometrial
Testicular