Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss

Tango Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; Non-Small Cell Adenocarcinoma; Brain Tumor; Lung Cancer; Glioma, Malignant; Non Small Cell Lung Cancer; Glioma Glioblastoma Multiforme

Treatments: Drug: TNG456; Drug: abemaciclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06810544

TNG456-C101

Details and patient eligibility

About

This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP loss. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific solid tumor types with a confirmed MTAP loss. The study drug, TNG456, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 191 participants.

Full description

This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed MTAP loss in their tumor. The Phase 1 portion is a dose escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Enrollment: 191 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a tumor with a confirmed MTAP loss
• Is ≥18 years of age at the time of signature of the main study ICF
• Has had progression or an inadequate response to or is intolerant of the approved standard of care therapy, no standard of care therapy exists, or the investigator has determined that treatment with the standard of care therapy is not appropriate.
• Is able to swallow tablets
• Adequate Organ function/reserve per local labs
• Negative serum pregnancy test result at screening
• Has an ECOG performance status score of 0 to 1
• Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.0.
• Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70.

Exclusion criteria

• A female patient is who is pregnant or breastfeeding
• Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s)
• Has an active infection requiring systemic therapy
• Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor
• Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor
• Clinically relevant cardiovascular disease
• Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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191 participants in 7 patient groups

Single Agent and Combination Dose Escalation

Experimental group

Description:

Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD

Treatment:

Drug: abemaciclib

Drug: TNG456

NSCLC Single Agent Dose Expansion

Experimental group

Description:

NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

Treatment:

Drug: TNG456

GBM Single Agent Dose Expansion

Experimental group

Description:

GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

Treatment:

Drug: TNG456

Tumor Agnostic Single Agent Dose Expansion

Experimental group

Description:

Patients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s)

Treatment:

Drug: TNG456

NSCLC Combination Expansion

Experimental group

Description:

NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

Treatment:

Drug: abemaciclib

Drug: TNG456

GBM Combination Expansion

Experimental group

Description:

GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

Treatment:

Drug: abemaciclib

Drug: TNG456

Tumor Agnostic Combination Expansion

Experimental group

Description:

Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

Treatment:

Drug: abemaciclib

Drug: TNG456