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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Breast Cancer; Pancreatic Cancer; Non Small Cell Lung Cancer; Endometrial Cancer; Solid Tumors, Adult; Carcinoma of Unknown Primary
• Intervention / Treatment: Drug: TNG260; Drug: Pembrolizumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tiffany Wang, MD; Phone Number: 8573204899; Email: clinicaltrials@tangotx.com

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Hematology/Oncology
      • Principal Investigator: Jonathan Goldman, MD
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • SCRI at Healthone
      • Principal Investigator: Gerald Falchook, MD
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Judy Wang, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Mark Awad, MD, PhD
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
      • Principal Investigator: Shiresh Gadgeel, MD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Health
      • Principal Investigator: Salman Punekar, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Tennessee Oncology
      • Principal Investigator: David Spigel, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Principal Investigator: Ferdinandos Skoulidis, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Oncology Virginia
      • Principal Investigator: Alex Spira, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD	Drug: TNG260; CoREST inhibitor, administered orally; Drug: Pembrolizumab; Pembrolizumab, an anti-PD-1 antibody, administered intravenously; Other Names: Keytruda
Experimental: Dose Expansion in NSCLC with KRAS Mutation; Participants with STK11-mutant and KRAS-mutant NSCLC (squamous and non squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab	Drug: TNG260; CoREST inhibitor, administered orally; Drug: Pembrolizumab; Pembrolizumab, an anti-PD-1 antibody, administered intravenously; Other Names: Keytruda
Experimental: Dose Expansion in NSCLC with KRAS Wild type; Participants with STK11-mutant and KRAS-wild type NSCLC (squamous and non-squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab	Drug: TNG260; CoREST inhibitor, administered orally; Drug: Pembrolizumab; Pembrolizumab, an anti-PD-1 antibody, administered intravenously; Other Names: Keytruda
Experimental: Dose Expansion in Advanced or Metastatic Solid Tumors; 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	Drug: TNG260; CoREST inhibitor, administered orally; Drug: Pembrolizumab; Pembrolizumab, an anti-PD-1 antibody, administered intravenously; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Tango Therapeutics, Inc.
• Investigators: Study Director: Tiffany Wang, MD, Tango Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: KRAS; STK11; LKB1
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: TNG260-C101

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