Clinical Trial Finder

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

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.

Arms

Experimental: Single Agent and Combination Dose Escalation

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

Experimental: NSCLC Single Agent Dose Expansion

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

Experimental: GBM Single Agent Dose Expansion

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

Experimental: Tumor Agnostic Single Agent Dose Expansion

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

Experimental: NSCLC Combination Expansion

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

Experimental: GBM Combination Expansion

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

Experimental: Tumor Agnostic Combination Expansion

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

Interventions

Drug: - TNG456

A selective PRMT5 inhibitor

Drug: - abemaciclib

A kinase inhibitor