TNG908 for Solid Tumors

Not currently recruiting at 21 trial locations

Overseen By Tango Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tango Therapeutics, Inc.

Must not be taking: Antiretrovirals

Disqualifiers: Active infection, Liver disease, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new oral treatment called TNG908 for individuals with advanced or hard-to-treat solid tumors, specifically those with an MTAP deletion. Researchers will explore different doses to determine the most effective one, focusing on specific cancer types such as sarcoma, glioblastoma, and mesothelioma. Suitable candidates for the trial have a confirmed MTAP-deleted tumor, have previously tried standard treatments, and meet basic health requirements. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that TNG908 is likely to be safe for humans?

In earlier studies, TNG908 showed potential in targeting certain cancer cells. This treatment focuses on tumors lacking a specific gene called MTAP. Research suggests that TNG908 affects a protein called PRMT5, which is crucial for the growth of these cancer cells.

Regarding safety, TNG908 remains in the early testing stages, so information about its effects on humans is limited. The current trial tests different doses to determine the safest and most effective amount. Researchers are still determining the exact safety details. During this trial phase, they carefully monitor for any side effects, and any serious issues would lead to dosage adjustments or even stopping the trial.

As TNG908 is being tested in humans for the first time, researchers are still learning about its tolerability. Participants are closely monitored for any unwanted effects, ensuring the treatment remains as safe as possible while more data is collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TNG908 because it targets tumors with MTAP deletions, a specific genetic alteration found in many cancers, including glioblastoma, sarcoma, and pancreatic ductal adenocarcinoma. Unlike standard chemotherapy or targeted therapies like EGFR inhibitors for NSCLC or temozolomide for glioblastoma, TNG908 is designed to exploit the unique vulnerabilities of MTAP-deleted tumors. This approach could potentially enhance the effectiveness of the treatment by specifically attacking cancer cells while sparing normal cells, leading to fewer side effects. By focusing on this novel mechanism of action, TNG908 represents a promising advancement in precision oncology, offering hope for improved outcomes in hard-to-treat cancers.

What evidence suggests that TNG908 might be an effective treatment for MTAP-deleted solid tumors?

Research has shown that TNG908 is a promising treatment for certain cancers with an MTAP deletion. TNG908 targets PRMT5, an enzyme essential for the growth of these cancer cells. Early studies suggest that TNG908 can reach the brain, potentially aiding in the treatment of brain tumors like glioblastoma. This trial includes various treatment arms where participants with MTAP-deleted tumors, such as glioblastoma, sarcoma, mesothelioma, and pancreatic cancer, receive TNG908. Although the data remains new, targeting MTAP-deleted tumors offers hope that TNG908 could be effective for several cancers. As research progresses, more information about its effectiveness will become available. ^{1 6 7 8 9}

Who Is on the Research Team?

Maxim Pimkin, MD, PhD

Principal Investigator

Tango Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults (18+) with advanced or metastatic solid tumors that lack the MTAP protein, confirmed by specific tests. Participants must have tried standard treatments if available, be in fairly good health with a performance score of 0 to 1 or ≥70, and have functioning major organs. Pregnant women and those with significant medical conditions, allergies to TNG908, uncontrolled illnesses affecting study compliance, active infections requiring therapy, other cancers, certain heart diseases or HIV not meeting specific criteria are excluded.

Inclusion Criteria

My tumor lacks the MTAP gene or protein.

I am fully active or able to carry out light work.

My kidney function is normal according to recent tests.

Exclusion Criteria

I am willing and able to follow the study's schedule and procedures.

I have another cancer besides the one being treated.

I am currently on medication for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with MTAP-deleted solid tumors receive escalating doses of TNG908 to estimate the MTD

16 weeks

Dose Expansion

Participants with specific MTAP-deleted tumor types receive TNG908 at the identified RP2D

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TNG908

Trial Overview TNG908 is being tested on patients with MTAP-deleted solid tumors. It's an oral drug designed to inhibit PRMT5. The trial has two parts: dose escalation to find the safe amount people can take without too many side effects and dose expansion focusing on how well it works in particular tumor types.

How Is the Trial Designed?

Group I: Dose Expansion in solid tumors Experimental Treatment 1 Intervention

Participants with other MTAP-deleted solid tumors will receive TNG908 at the identified RP2D

Group II: Dose Expansion in Sarcoma Experimental Treatment 1 Intervention

Participants with MTAP-deleted sarcoma (soft tissue and bone) will receive TNG908 at the identified RP2D

Group III: Dose Expansion in Pancreatic Ductal Adenocarcinoma Experimental Treatment 1 Intervention

Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG908 at the identified RP2D

Group IV: Dose Expansion in NSCLC Experimental Treatment 1 Intervention

Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG908 at the identified RP2D

Group V: Dose Expansion in Mesothelioma Experimental Treatment 1 Intervention

Participants with MTAP-deleted mesothelioma will receive TNG908 at the identified RP2D

Group VI: Dose Expansion in Glioblastoma Experimental Treatment 1 Intervention

Participants with MTAP-deleted relapsed/refractory glioblastoma will receive TNG908 at the identified RP2D

Group VII: Dose Escalation Experimental Treatment 1 Intervention

Participants with MTAP-deleted solid tumors will receive escalating doses of TNG908 to estimate the MTD

Who Is Running the Clinical Trial?

Tango Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

740+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05275478

Safety and Tolerability of TNG908 in Patients With MTAP- ... This is a Phase 1/2 multi-center, open label study in solid tumor patients (including glioblastoma) who have a confirmed homozygous MTAP deletion in their tumor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11832951/

TNG908 is a brain-penetrant, MTA-cooperative PRMT5 ... TNG908 is being tested clinically in a phase I/II trial in MTAP-deleted solid tumors including glioblastoma (NCT05275478). Introduction. The ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05275478

TNG908 in Patients With MTAP-deleted Solid Tumors 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500224004975

MTAP as an emerging biomarker in thoracic malignancies In a retrospective analysis, patients with MTAP deficient lung adenocarcinoma responded significantly better to a combination therapy with pemetrexed and ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39756156/

TNG908 is a brain-penetrant, MTA-cooperative PRMT5 ... TNG908 is being tested clinically in patients with MTAP-deleted tumors, including glioblastoma, in a Phase I/II clinical trial (NCT05275478). Keywords: MTA- ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20574135

Safety and Tolerability of TNG908 in Patients With MTAP ... Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors ... safety, side effects, optimal dosages and risks/benefits.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1936523324003905

TNG908 is a brain-penetrant, MTA-cooperative PRMT5 ... TNG908 drives strong antitumor activity, including sustained tumor regressions, in MTAP-deleted xenograft models representing multiple tumor histologies ...

8. braintumorcenter.ucsf.edu braintumorcenter.ucsf.edu/clinical-trial/phase-iii-multicenter-open-label-study-evaluate-safety-tolerability-and-preliminary

A Phase I/II Multicenter, Open-Label Study to Evaluate ... Elevated levels of MTA are found in tumor cells that have lost the MTAP gene, conveying specificity of TNG908 to tumor cells that have lost MTAP over normal ...

9. ejcancer.com ejcancer.com/article/S0959-8049(22)01021-8/fulltext

TNG908 is a brain-penetrant, MTA-cooperative PRMT5 ... TNG908 is a clinical stage MTA-cooperative PRMT5 inhibitor that leverages the synthetic lethal interaction between PRMT5 inhibition and MTAP deletion.