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

• ClinicalTrials.gov Identifier: NCT05887492
• Recruitment Status: Recruiting
• First Posted: June 2, 2023
• Last Update Posted: March 26, 2024
• Sponsor: Tango Therapeutics, Inc.
• Information provided by (Responsible Party): Tango Therapeutics, Inc.

Tracking Information

• First Submitted Date: April 18, 2023
• First Posted Date: June 2, 2023
• Last Update Posted Date: March 26, 2024
• Actual Study Start Date: June 12, 2023
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2023)

• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 24, 2023)

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors
• 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

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 Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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

Condition

• Non Small Cell Lung Cancer
• Solid Tumors, Adult
• Endometrial Cancer
• Pancreatic Cancer
• Cervical Cancer
• Breast Cancer
• Carcinoma of Unknown Primary

Intervention

• Drug: TNG260
  CoREST inhibitor, administered orally
• Drug: Pembrolizumab
  Pembrolizumab, an anti-PD-1 antibody, administered intravenously
  Other Name: Keytruda

Study Arms

• Experimental: Dose Escalation
  Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD
  Interventions:

  • Drug: TNG260
  • Drug: Pembrolizumab
• 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
  Interventions:

  • Drug: TNG260
  • Drug: Pembrolizumab
• 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
  Interventions:

  • Drug: TNG260
  • Drug: Pembrolizumab
• 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
  Interventions:

  • Drug: TNG260
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 24, 2023): 126
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tiffany Wang, MD; 8573204899; clinicaltrials@tangotx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05887492
• Other Study ID Numbers: TNG260-C101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tango Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tango Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Tango Therapeutics, Inc.
• Verification Date: March 2024