Clinical trial NCT05887492: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Solid Tumors, Adult
Lung Cancer
Lung Adenocarcinoma
Keywords: STK11
KRAS wild type
LKB1
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion)
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determine the MTD and RP2D(s) (Phase 1 only)
timeFrame: 42 days
measure: Measure antitumor activity using RECIST 1.1 (Phase 2 only)
timeFrame: 12 weeks
Secondary outcomes:
measure: Measure antitumor evidence of TNG260 + pembrolizumab antineoplastic activity by RECIST 1.1 (Phase 1 only)
timeFrame: 12 weeks
measure: Characterize Area Under the Curve (AUC) of TNG260
timeFrame: 37 days
measure: Characterize the time to achieve Time to Maximal Concentration (Tmax) of TNG260
timeFrame: 37 days
measure: Characterize Maximum Observed Plasma Concentration (Cmax) of TNG260
timeFrame: 37 days
measure: Characterize Terminal Half-life (T1/2) of TNG260
timeFrame: 37 days
measure: Characterize pembrolizumab concentrations when administered with TNG260
timeFrame: 43 days
measure: Safety and tolerability of TNG260 by CTCAE 5.0
timeFrame: 42 days
measure: To measure changes in histone acetylation when administered with TNG260
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Denver
country: United States
facility: SCRI at HealthOne
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: START MidWest
state: Michigan
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Adam Crystal, MD, PhD
role: STUDY_DIRECTOR
References: