TNG462 for Solid Cancers

Recruiting at 26 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, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, TNG462, to determine its effectiveness in people with advanced solid tumors that have a specific genetic deletion called MTAP. Researchers aim to find the best dose and assess its efficacy in various tumor types, including pancreatic cancer and sarcoma. The trial seeks participants who have already tried standard treatments and whose tumors lack the MTAP protein, which specific tests can confirm. As a Phase 1 trial, this research focuses on understanding how TNG462 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

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

Is there any evidence suggesting that TNG462 is likely to be safe for humans?

Research has shown that TNG462, also known as Vopimetostat, has been tested for safety in patients with MTAP-deleted cancer. In these studies, TNG462 was generally safe, with most patients tolerating it without serious issues. Some side effects occurred but were usually manageable. As these trials continue, more information will emerge. Since this is a Phase 1/2 study, researchers are still determining the safest dose. This phase is crucial for understanding how well patients can tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for solid tumors, which often include chemotherapy, radiation, or surgery, TNG462 targets MTAP-deleted cancers with a novel mechanism of action. This treatment works by exploiting a specific genetic vulnerability in cancer cells, potentially leading to more precise targeting of the tumor cells while sparing healthy ones. Researchers are excited about TNG462 because it not only offers a new approach to treating difficult cancers like pancreatic ductal adenocarcinoma, sarcoma, and mesothelioma but also shows promise in combination with pembrolizumab for enhanced effectiveness. This targeted approach could lead to more effective treatments with potentially fewer side effects compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that TNG462 may help treat certain cancers with a specific genetic change called MTAP-deletion. In studies, about 27% of patients experienced tumor shrinkage, meaning roughly one in four people saw positive results. Additionally, 78% of patients experienced either no tumor growth or a reduction in tumor size, which is promising. TNG462 works by blocking a protein called PRMT5, which cancer cells need to grow. This trial will explore TNG462's effectiveness in various treatment arms, including those for pancreatic ductal adenocarcinoma, sarcoma, and other solid tumors. Some arms will also investigate TNG462 in combination with pembrolizumab for non-small cell lung cancer (NSCLC). These findings suggest that TNG462 could be a useful option for patients with these specific genetic tumor types. ^{1 2 5 6 7}

Who Is on the Research Team?

Maeve Waldron-Lynch, MD

Principal Investigator

Tango Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have an MTAP deletion. They should have tried standard treatments, be in fairly good health (ECOG score of 0-1), and have no major organ issues. Pregnant or breastfeeding women, those with allergies to TNG462, uncontrolled illnesses, other cancer treatments ongoing or planned, significant GI absorption issues, active serious infections or liver disease are excluded.

Inclusion Criteria

My tumor lacks the MTAP gene or protein.

Negative serum pregnancy test result at screening

Written informed consent must be obtained according to local guidelines

Exclusion Criteria

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

I have heart problems that affect my daily life.

I have another active cancer besides the one being studied.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of TNG462 as a single agent and in combination with pembrolizumab to estimate the maximum tolerated dose

4 weeks

Multiple visits (in-person)

Dose Expansion

Participants receive TNG462 at the identified recommended phase 2 dose (RP2D) in specific MTAP-deleted tumor types

16-18 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TNG462

Trial Overview The study tests TNG462's safety and how well patients tolerate it. It's a first-in-human study with two parts: dose escalation to find the safe amount to give people and then dose expansion focusing on specific tumor types. Up to 159 participants will take this oral PRMT5 inhibitor.

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 TNG462 at the identified RP2D(s)

Group II: Dose Expansion in Sarcoma Experimental Treatment 1 Intervention

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

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

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

Group IV: Dose Expansion in NSCLC in Combination with Pembrolizumab Experimental Treatment 2 Interventions

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

Group V: Dose Expansion in NSCLC Experimental Treatment 1 Intervention

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

Group VI: Dose Expansion in Mesothelioma Experimental Treatment 1 Intervention

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

Group VII: Dose Escalation Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Tango Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

740+

Citations

1. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.4c03067

Discovery of TNG462: A Highly Potent and Selective MTA ... TNG462 has strong efficacy across a panel of both cell-derived and patient-derived xenograft models including those representing pancreatic, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05732831

Safety and Tolerability of TNG462 in Patients With MTAP- ... 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 ...

3. tangotx.gcs-web.com tangotx.gcs-web.com/news-releases/news-release-details/tango-therapeutics-reports-positive-data-ongoing-phase-12-study

News Release Details Tango Therapeutics Reports Positive Data from Ongoing Phase 1/2 Study with Vopimetostat (TNG462) in Patients with MTAP-deleted Cancers.

4. onclive.com onclive.com/view/vopimetostat-demonstrates-early-evidence-of-efficacy-in-mtap-deleted-solid-tumors

Vopimetostat Demonstrates Early Evidence of Efficacy in ... Tango Therapeutics reports positive data from ongoing phase 1/2 study with vopimetostat (TNG462) in patients with MTAP-deleted Cancers. News ...

5. clinicaltrials.eu clinicaltrials.eu/inn/tng462/

TNG462: A Promising New Drug for MTAP-Deleted Solid ... TNG462 is a new drug currently being studied for its potential to treat certain types of cancer. It is described as a selective PRMT5 inhibitor.

6. careacross.com careacross.com/clinical-trials/trial/NCT05732831

Safety and Tolerability of TNG462 in Patients With MTAP ... Detailed 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.

7. cancer.gov cancer.gov/clinicaltrials/NCI-2023-06124

Safety and Tolerability of TNG462 in Patients With MTAP ... The study drug, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.