Lung Adenocarcinoma, Lung Cancer, Non Small Cell Lung Cancer, Solid Tumors, Adult
Conditions
Keywords
STK11, KRAS wild type, LKB1
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.
Interventions
DRUGTNG260
CoREST inhibitor, administered orally
DRUGPembrolizumab
Pembrolizumab, an anti-PD-1 antibody, administered intravenously
Sponsors
Tango Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 (Dose Escalation) and Phase 2 (Dose Expansion)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Contacts
STUDY_DIRECTORAdam Crystal, MD, PhD
Tango Therapeutics, Inc.
Outcome results
None listed