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

Phase 2RecruitingNCT05887492

Tango Therapeutics, Inc.126 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

126

Conditions

Non Small Cell Lung Cancer Solid Tumors, Adult

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

UCLA Hematology/Oncology

Santa Monica, California, United States

RECRUITING

SCRI at HealthOne

Denver, Colorado, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, United States

RECRUITING

START MidWest

Grand Rapids, Michigan, United States

RECRUITING

NYU Langone Hematology Oncology Associates-Mineola

Mineola, New York, United States

RECRUITING

New York University Langone Health

New York, New York, United States

RECRUITING

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, United States

RECRUITING

US Oncology Investigational Products Center

Dallas, Texas, United States

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

Determine the MTD and RP2D(s) (Phase 1 only)

To determine the MTD and RP2D(s) of TNG260 when administered in combination with pembrolizumab

Time frame: 42 days

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

Time frame: 12 weeks

Secondary Outcomes

Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only)

Time frame: 12 weeks

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

Time frame: 37 days

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

Time frame: 37 days

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

Time frame: 37 days

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

Time frame: 37 days

Characterize pembrolizumab concentrations when administered with TNG260

To characterize the pre treatment and trough concentration levels of pembrolizumab when administered in combination with TNG260

Time frame: 43 days

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

Time frame: 42 days

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

Time frame: 12 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts