Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

Tango Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Locally Advanced Solid Tumor

Treatments: Drug: Pembrolizumab; Drug: TNG462

Study type: Interventional

Funder types: Industry

Identifiers

NCT05732831

TNG462-C101

Details and patient eligibility

About

This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.

Full description

This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG462 administered as a single agent and in combination with pembrolizumab in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D(s) of TNG462 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.

Enrollment: 225 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age: ≥18 years-of-age at the time of signature of the main study ICF
2. Performance status: ECOG Performance Score of 0 to 1
3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor
4. Prior standard therapy, as available
5. Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next- generation sequencing or absence of MTAP protein in a tumor detected by IHC.
6. Adequate organ function/reserve per local labs
7. Adequate liver function per local labs
8. Adequate renal function per local labs
9. Negative serum pregnancy test result at screening
10. Written informed consent must be obtained according to local guidelines

Exclusion criteria

1. Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or to pembrolizumab in the combination treatment arms

2. Uncontrolled intercurrent illness that will limit compliance with the study requirements

3. Active infection requiring systemic therapy

4. Currently participating in or has planned participation in a study of another investigational agent or device

5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG462

6. Active prior or concurrent malignancy.

7. Central nervous system metastases associated with progressive neurological symptoms

8. Current active liver disease from any cause

9. Known to be HIV positive, unless all of the following criteria are met:

   1. CD4+ count ≥300/μL
   2. Undetectable viral load
   3. Receiving highly active antiretroviral therapy

10. Clinically relevant cardiovascular disease

11. A female patient who is pregnant or lactating

12. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions

13. Patient has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the safety of the patient or impair the assessment of study results

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

225 participants in 7 patient groups

Dose Escalation

Experimental group

Description:

Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 single agent and in combination with pembrolizumab to estimate the MTD

Treatment:

Drug: TNG462

Drug: Pembrolizumab

Dose Expansion in NSCLC

Experimental group

Description:

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Dose Expansion in Mesothelioma

Experimental group

Description:

Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Dose Expansion in Pancreatic Ductal Adenocarcinoma

Experimental group

Description:

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Dose Expansion in Sarcoma

Experimental group

Description:

Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Dose Expansion in Solid Tumors

Experimental group

Description:

Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Dose Expansion in NSCLC in Combination with Pembrolizumab

Experimental group

Description:

Participants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)

Treatment:

Drug: TNG462

Drug: Pembrolizumab