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

Primary Purpose

Non Small Cell Lung Cancer, Solid Tumors, Adult, Endometrial Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TNG260
Pembrolizumab
Sponsored by
Tango Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring STK11, KRAS, LKB1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • SCRI at HealthOneRecruiting
  • Florida Cancer SpecialistsRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • New York University Langone HealthRecruiting
  • Sarah Cannon Tennessee OncologyRecruiting
  • NEXT OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Escalation

Dose Expansion in NSCLC with KRAS Mutation

Dose Expansion in NSCLC with KRAS Wild type

Dose Expansion in Advanced or Metastatic Solid Tumors

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

Determine the MTD and RP2D(s) (Phase 1 only)
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)
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

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
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
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
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
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
Characterize pembrolizumab concentrations when administered with TNG260
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
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
Measure changes in levels of histone acetylation in blood and/or tumor tissue, on study treatment relative to pre-treatment

Full Information

First Posted
April 18, 2023
Last Updated
October 24, 2023
Sponsor
Tango Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05887492
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 12, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tango Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Solid Tumors, Adult, Endometrial Cancer, Pancreatic Cancer, Cervical Cancer, Breast Cancer, Carcinoma of Unknown Primary
Keywords
STK11, KRAS, LKB1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion)
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD
Arm Title
Dose Expansion in NSCLC with KRAS Mutation
Arm Type
Experimental
Arm Description
Participants with STK11-mutant and KRAS-mutant NSCLC (squamous and non squamous) will receive TNG260 at the identified RP2D in combination with pembrolizumab
Arm Title
Dose Expansion in NSCLC with KRAS Wild type
Arm Type
Experimental
Arm 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
Arm Title
Dose Expansion in Advanced or Metastatic Solid Tumors
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
TNG260
Intervention Description
CoREST inhibitor, administered orally
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab, an anti-PD-1 antibody, administered intravenously
Primary Outcome Measure Information:
Title
Determine the MTD and RP2D(s) (Phase 1 only)
Description
To determine the MTD and RP2D(s) of TNG260 when administered in combination with pembrolizumab
Time Frame
42 days
Title
Measure antitumor activity using RECIST 1.1 (Phase 2 only)
Description
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
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only)
Description
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
Time Frame
12 weeks
Title
Characterize Area Under the Curve (AUC) of TNG260
Description
Measure the plasma concentration versus time curve (AUC) of TNG260 alone and when administered in combination with pembrolizumab
Time Frame
37 days
Title
Characterize the time to achieve Time to Maximal Concentration (Tmax) of TNG260
Description
To characterize the Tmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab
Time Frame
37 days
Title
Characterize Maximum Observed Plasma Concentration (Cmax) of TNG260
Description
To characterize the Cmax by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab
Time Frame
37 days
Title
Characterize Terminal Half-life (T1/2) of TNG260
Description
To characterize the T1/2 by measuring the plasma concentrations versus time of TNG260 alone and when administered in combination with pembrolizumab
Time Frame
37 days
Title
Characterize pembrolizumab concentrations when administered with TNG260
Description
To characterize the pre treatment and trough concentration levels of pembrolizumab when administered in combination with TNG260
Time Frame
43 days
Title
Safety and tolerability of TNG260 by CTCAE 5.0
Description
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
Time Frame
42 days
Title
To measure changes in histone acetylation when administered with TNG260
Description
Measure changes in levels of histone acetylation in blood and/or tumor tissue, on study treatment relative to pre-treatment
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Adam Crystal, MD, PhD
Phone
8573204899
Email
clinicaltrials@tangotx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam Crystal, MD, PhD
Organizational Affiliation
Tango Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
SCRI at HealthOne
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerald Falchook, MD
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Judy Wang, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Awad, MD, PhD
Facility Name
New York University Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salman Punekar, MD
Facility Name
Sarah Cannon Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Spigel, MD
Facility Name
NEXT Oncology
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alex Spira, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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