Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination With an Anti-PD-1 Antibody In Patients With STK11 Mutated Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05887492
• Other study ID #: TNG260-C101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 12, 2023
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Tango Therapeutics, Inc.
• Contact: Tiffany Wang, MD
• Phone: 8573204899
• Email: clinicaltrials[@]tangotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional clinical trial is to learn about TNG260, a CoREST inhibitor, in combination with pembrolizumab in patients with advanced solid tumors with a known STK11 mutation. The main question[s] it aims to answer are: - the recommended dose for Phase 2 - to evaluate the safety and tolerability of the combination therapy - to determine the pharmacokinetics of TNG260 - to evaluate the initial antineoplastic activity Participants will receive study treatment until they experience an undesirable side effect, their disease progresses or until they withdraw consent.

Description:

This is a first-in-human Phase 1/2, open-label, multicenter, dose-escalation and expansion study designed to determine the maximum tolerated dose and recommended phase 2 dose(s) and evaluate the safety and tolerability, pharmacokinetics, and antineoplastic activity of escalating oral doses of TNG260 when administered with a standard dose of pembrolizumab in participants with locally advanced or metastatic STK11 mutated solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: June 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Is =18 years of age at the time of signature of the main study ICF.
• Has ECOG performance status of 0 or 1.
• Has measurable disease based on RECIST v1.1.
• All participants must have documented STK11 mutation in a solid tumor, which is identified through a validated analytical method
• Has confirmed histologic or cytologic diagnosis of a locally advanced or metastatic solid tumor.
• Adequate organ function/reserve per local labs
• Adequate liver function per local labs
• Adequate renal function per local labs
• Negative serum pregnancy test result at screening
• Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to TNG260, PD-1 antibody or its excipients
• Uncontrolled intercurrent illness that will limit compliance with the study requirements
• Active infection requiring systemic therapy
• Currently participating in or has planned participation in a study of another investigational agent or device
• Impairment of GI function or disease that may significantly alter the absorption of oral TNG260
• Active prior or concurrent malignancy.
• Central nervous system metastases associated with progressive neurological symptoms
• Current active liver disease from any cause
• Clinically relevant cardiovascular disease
• A female patient who is pregnant or lactating

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma of Unknown Primary
• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Non Small Cell Lung Cancer
• Pancreatic Cancer
• Solid Tumors, Adult

Intervention

Drug:
• TNG260
CoREST inhibitor, administered orally
• Pembrolizumab
Pembrolizumab, an anti-PD-1 antibody, administered intravenously

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	SCRI at HealthOne	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Tennessee Oncology	Nashville	Tennessee
United States	New York University Langone Health	New York	New York
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tango Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the MTD and RP2D(s) (Phase 1 only)	To determine the MTD and RP2D(s) of TNG260 when administered in combination with pembrolizumab	42 days
Primary	Measure antitumor activity using RECIST 1.1 (Phase 2 only)	To assess antineoplastic activity of TNG260 when administered in combination with pembrolizumab in participants with locally advanced unresectable or metastatic STK11-mutated solid tumors by measuring ORR, DOR, and PFS by RECIST 1.1	12 weeks
Secondary	Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only)	To assess antineoplastic activity of TNG260 when administered in combination with pembrolizumab in participants with locally advanced unresectable or metastatic STK11-mutated solid tumors by measuring ORR, DOR, and PFS by RECIST 1.1	12 weeks
Secondary	Characterize Area Under the Curve (AUC) of TNG260	Measure the plasma concentration versus time curve (AUC) of TNG260 alone and when administered in combination with pembrolizumab	37 days
Secondary	Characterize the time to achieve Time to Maximal Concentration (Tmax) of TNG260	To characterize the Tmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab	37 days
Secondary	Characterize Maximum Observed Plasma Concentration (Cmax) of TNG260	To characterize the Cmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab	37 days
Secondary	Characterize Terminal Half-life (T1/2) of TNG260	To characterize the T1/2 by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab	37 days
Secondary	Characterize pembrolizumab concentrations when administered with TNG260	To characterize the pre treatment and trough concentration levels of pembrolizumab when administered in combination with TNG260	43 days
Secondary	Safety and tolerability of TNG260 by CTCAE 5.0	To evaluate the safety and tolerability of TNG260 when administered as single agent and in combination with pembrolizumab by measuring the incidence, nature, and severity of AE and SAE graded according to CTCAE v5.0	42 days
Secondary	To measure changes in histone acetylation when administered with TNG260	Measure changes in levels of histone acetylation in blood and/or tumor tissue, on study treatment relative to pre-treatment	12 weeks