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

Sponsor
Tango Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05887492
Collaborator
(none)
126
1
4
24
5.3

Study Details

Study Description

Brief 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.

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 Design

Study Type:
Interventional
Anticipated Enrollment :
126 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion)Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion)
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jun 2, 2023
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Determine the MTD and RP2D(s) (Phase 1 only) [42 days]

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

    2. Measure antitumor activity using RECIST 1.1 (Phase 2 only) [12 weeks]

      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

    Secondary Outcome Measures

    1. Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only) [12 weeks]

      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

    2. Characterize Area Under the Curve (AUC) of TNG260 [37 days]

      Measure the plasma concentration versus time curve (AUC) of TNG260 alone and when administered in combination with pembrolizumab

    3. Characterize the time to achieve Time to Maximal Concentration (Tmax) of TNG260 [37 days]

      To characterize the Tmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab

    4. Characterize Maximum Observed Plasma Concentration (Cmax) of TNG260 [37 days]

      To characterize the Cmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab

    5. Characterize Terminal Half-life (T1/2) of TNG260 [37 days]

      To characterize the T1/2 by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab

    6. Characterize pembrolizumab concentrations when administered with TNG260 [43 days]

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

    7. Safety and tolerability of TNG260 by CTCAE 5.0 [42 days]

      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

    8. To measure changes in histone acetylation when administered with TNG260 [12 weeks]

      Measure changes in levels of histone acetylation in blood and/or tumor tissue, on study treatment relative to pre-treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 NEXT Oncology Fairfax Virginia United States 22031

    Sponsors and Collaborators

    • Tango Therapeutics, Inc.

    Investigators

    • Study Director: Adam Crystal, MD, PhD, Tango Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tango Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT05887492
    Other Study ID Numbers:
    • TNG260-C101
    First Posted:
    Jun 2, 2023
    Last Update Posted:
    Jun 8, 2023
    Last Verified:
    Jun 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Tango Therapeutics, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 8, 2023