First in Human Study of TORL-2-307-MAB in Participants With Advanced Cancer

A Phase 1, First in Human, Dose-Escalation Study of TORL-2-307-MAB in Participants With Advanced Cancer

This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of TORL-2-307-MAB in patients with advanced cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Advanced Solid Tumor; Pancreas Cancer; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: TORL-2-307-MAB

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
• United States
  • California
    • Fullerton, California, United States, 92835
      • Providence St. Jude Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA - JCCC Clinical Research Unit
    • Torrance, California, United States, 90505
      • Torrance Memorial Medical
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School OF Medicine-Siteman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≤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-2-307-MAB
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Dose Finding - Part 1; TORL-2-307-MAB	Drug: TORL-2-307-MAB; monoclonal antibody
Experimental: Expansion as Monotherapy - Part 2; TORL-2-307-MAB	Drug: TORL-2-307-MAB; monoclonal antibody

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1	up to 2 years
Duration of Response (DOR)	Time from CR or PR to objective disease progression or death to any cause	up to 2 years
Progression Free Survival (PFS)	PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause	up to 2 years
Time to Response (TTR)	Time from start of treatment to complete response or partial response	up to 2 years
1 Year Overall Survival (1YOS)	Proportion of participants alive at 1 year from the start of treatment to death from any cause	1 year
2 Year Overall Survival (2YOS)	Proportion of participants alive at 2 years from the start of treatment to death from any cause	2 years
Number of anti-drug antibody (ADA) Positive Participants	Immunogenicity will be measured by the number of participants that are ADA positive.	up to 2 years
Maximum Serum Concentration of TORL-2-307-MAB (Cmax)	PK assessment	21 days
Minimum Serum Concentration of TORL-2-307-MAB (Cmin)	PK assessment	21 days
Maximum Serum Concentration of TORL-2-307-MAB at Steady State (Cmax,ss)	PK assessment	63 days
Minimum Serum Concentration of TORL-2-307-MAB at Steady State (Cmin,ss)	PK assessment	63 days
Time of Maximum Serum Concentration of TORL-2-307-MAB (Tmax)	PK assessment	21 days
Time of Minimum Serum Concentration of TORL-2-307-MAB (Tmin)	PK Assessment	21 days
Time of Minimum Serum Concentration of TORL-2-307-MAB at Steady State (Tmin,ss)	PK Assessment	63 days
Terminal Half-life (t1/2) of Serum TORL-2-307-MAB	PK Assessment	63 days
Apparent volume of distribution during the terminal phase (Vz) of TORL-2-307-MAB	PK Assessment	63 days
Clearance (CL) of TORL-2-307-MAB	PK Assessment	63 days
Accumulation ratio (Rac) of TORL-2-307-MAB	PK Assessment	63 days
Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-2-307-MAB	PK Assessment	21 days
Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-2-307-MAB	PK Assessment	63 days

Collaborators and Investigators

• Sponsor: TORL Biotherapeutics, LLC
• Collaborators: Translational Research in Oncology
• Investigators: Study Director: Stephen Letrent, PharmD, PhD, TORL Biotherapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: claudin18.2
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: TORL2307MAB-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No