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

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ClinicalTrials.gov Identifier: NCT05887492
Recruitment Status : Recruiting
First Posted : June 2, 2023
Last Update Posted : August 15, 2023
Sponsor:
Information provided by (Responsible Party):
Tango Therapeutics, Inc.

Study Description
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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.


Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Solid Tumors, Adult Endometrial Cancer Pancreatic Cancer Cervical Cancer Breast Cancer Carcinoma of Unknown Primary Drug: TNG260 Drug: Pembrolizumab Phase 1 Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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
Actual Study Start Date : June 12, 2023
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: Keytruda


Outcome Measures
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Primary Outcome Measures :
  1. Determine the MTD and RP2D(s) (Phase 1 only) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 12 weeks ]
    Measure changes in levels of histone acetylation in blood and/or tumor tissue, on study treatment relative to pre-treatment


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05887492


Contacts
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Contact: Adam Crystal, MD, PhD 8573204899 clinicaltrials@tangotx.com

Locations
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United States, Colorado
SCRI at HealthOne Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Gerald Falchook, MD         
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Principal Investigator: Judy Wang, MD         
United States, New York
New York University Langone Health Recruiting
New York, New York, United States, 10016
Principal Investigator: Salman Punekar, MD         
United States, Tennessee
Sarah Cannon Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: David Spigel, MD         
United States, Virginia
NEXT Oncology Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alex Spira, MD         
Sponsors and Collaborators
Tango Therapeutics, Inc.
Investigators
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Study Director: Adam Crystal, MD, PhD Tango Therapeutics, Inc.
More Information
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Responsible Party: Tango Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05887492    
Other Study ID Numbers: TNG260-C101
First Posted: June 2, 2023    Key Record Dates
Last Update Posted: August 15, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tango Therapeutics, Inc.:
STK11
KRAS
LKB1
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Neoplasms by Site
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action