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

Tango Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Lung Cancer; Non Small Cell Lung Cancer; Solid Tumors, Adult; Lung Adenocarcinoma

Treatments: Drug: TNG260; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05887492

TNG260-C101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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126 participants in 4 patient groups

Dose Escalation

Experimental group

Description:

Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD

Treatment:

Drug: Pembrolizumab

Drug: TNG260

Dose Expansion in NSCLC with KRAS Mutation

Experimental group

Description:

Participants with STK11-mutant and KRAS-mutant NSCLC (squamous and non squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab

Treatment:

Drug: Pembrolizumab

Drug: TNG260

Dose Expansion in NSCLC with KRAS Wild type

Experimental group

Description:

Participants with STK11-mutant and KRAS-wild type NSCLC (squamous and non-squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab

Treatment:

Drug: Pembrolizumab

Drug: TNG260

Dose Expansion in Advanced or Metastatic Solid Tumors

Experimental group

Description:

Participants with STK11-mutant solid tumors (including but not limited to pancreatic, endometrial, cervical, breast, and carcinoma of unknown primary) will receive TNG260 at the identified RP2D in combination with pembrolizumab

Treatment:

Drug: Pembrolizumab

Drug: TNG260