A Phase 1, First in Human Study of TORL-4-500 in Patients With Advanced Cancer

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; Hepatocellular Carcinoma
• Interventions: Drug: TORL-4-500

• Registration Number: NCT06005740
• Lead Sponsor: TORL Biotherapeutics, LLC

Brief Summary

This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-4-500 in patients with advanced cancer.

For Part 1, any advanced or metastatic solid tumor malignancy will be evaluated including, for example, adrenocortical carcinoma (ACC).

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2023-08-15
• Study First Submitted QC: 2023-08-15
• Study First Posted: 2023-08-22
• Study Start: 2023-12-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-18
• Last Update Posted: 2024-10-22
• Primary Completion: 2025-10-31
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Advanced solid tumor
• Measurable disease, per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate organ function

Read More

Exclusion Criteria

• Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤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-4-500
• 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy Dose Dose Finding - Part 1	TORL-4-500	TORL-4-500 iv once every 3 weeks
Expansion as Monotherapy - Part 2	TORL-4-500	TORL-4-500 iv once every 3 weeks

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	28 Days	Highest administered dose with \< 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants
Recommended Phase 2 Dose (RP2D)	up to 2 years	Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data
Incidence and severity of adverse events and serious adverse events	up to 2 years	Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	up to 2 years	Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1
Duration of Response (DOR)	up to 2 years	Time from CR or PR to objective disease progression or death to any cause
Progression Free Survival (PFS)	up to 2 years	PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause
Time to Response (TTR)	up to 2 years	Time from start of treatment to complete response or partial response
1 Year Overall Survival (1YOS)	1 year	Proportion of participants alive at 1 year from the start of treatment to death from any cause
2 Year Overall Survival (2YOS)	2 years	Proportion of participants alive at 2 years from the start of treatment to death from any cause
Number of anti-drug antibody (ADA) Positive Participants	up to 2 years	Immunogenicity will be measured by the number of participants that are ADA positive.
Maximum Serum Concentration of TORL-4-500 (Cmax)	21 days	PK assessment
Minimum Serum Concentration of TORL-4-500 (Cmin)	21 days	PK assessment
Maximum Serum Concentration of TORL-4-500 at Steady State (Cmax,ss)	63 days	PK assessment
Minimum Serum Concentration of TORL-4-500 at Steady State (Cmin,ss)	63 days	PK assessment
Time of Maximum Serum Concentration of TORL-4-500 (Tmax)	21 days	PK assessment
Time of Minimum Serum Concentration of TORL-4-500 (Tmin)	21 days	PK Assessment
Time of Minimum Serum Concentration of TORL-4-500 at Steady State (Tmin,ss)	63 days	PK Assessment
Terminal Half-life (t1/2) of Serum TORL-4-500-ADC	63 days	PK Assessment
Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-4-500	21 days	PK Assessment
Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-4-500	63 days	PK Assessment
Apparent volume of distribution during the terminal phase (Vz) of TORL-4-500	63 days	PK Assessment
Clearance (CL) of TORL-4-500	63 days	PK Assessment
Accumulation ratio (Rac) of TORL-4-500	63 days	PK Assessment

Trial Locations

Locations (5)

Torrance Memorial Physician Network; 🇺🇸 Torrance, California, United States

McGill University Health Centre; 🇨🇦 Montréal, Quebec, Canada

Providence Medical Foundation; 🇺🇸 Fullerton, California, United States

UCLA - JCCC Clinical Research Unit; 🇺🇸 Los Angeles, California, United States

University Health Network, Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada