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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05732831
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Tango Therapeutics, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Maeve Waldron-Lynch, MD
Principal Investigator Affiliation	Tango Therapeutics, Inc.
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	France, Spain, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Locally Advanced Solid Tumor

Additional Details

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.

Arms & Interventions

Arms

Experimental: Dose Escalation

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

Experimental: Dose Expansion in NSCLC

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

Experimental: Dose Expansion in Mesothelioma

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

Experimental: Dose Expansion in Pancreatic Ductal Adenocarcinoma

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

Experimental: Dose Expansion in Sarcoma

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

Experimental: Dose Expansion in Solid Tumors

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

Experimental: Dose Expansion in NSCLC in Combination with Pembrolizumab

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

Interventions

Drug: - TNG462

TNG462, a selective PRMT5 inhibitor, will be administered orally

Drug: - Pembrolizumab

An anti PD-1 antibody, will be administered intravenously

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Stanford University, Palo Alto 5380748, California 5332921

Status

Recruiting

Address

Stanford University

Palo Alto 5380748, California 5332921, 94304

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