TNG456 + Abemaciclib for Solid Tumors

Recruiting at 10 trial locations

Overseen By Maeve Waldron-Lynch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tango Therapeutics, Inc.

Must not be taking: PRMT5 inhibitors, MAT2A inhibitors, CDK4/6 inhibitors

Disqualifiers: Pregnancy, Active infection, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

191 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment, TNG456, for individuals with advanced solid tumors that have a specific genetic change called MTAP loss. The trial aims to determine the optimal dose and evaluate its effectiveness alone or with abemaciclib, a drug already used in cancer treatments. Participants must have tumors with confirmed MTAP loss and have tried other treatments that were ineffective or unsuitable. The trial includes different groups based on tumor types, such as lung and brain cancers. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

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 this trial's treatments are likely to be safe?

Research has shown that TNG456, whether taken alone or with abemaciclib, appears safe. As of June 16, 2025, participants have tolerated TNG456 well at a dose of 250 mg once daily, which is the planned dose for future use.

Although this study remains in its early stages, these results suggest the treatment is safe at this dose. However, individual experiences may vary. The combination with abemaciclib is undergoing its first human tests, so ongoing monitoring will offer more information about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TNG456 and its combination with abemaciclib because these treatments target solid tumors with a specific genetic feature: MTAP loss. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, TNG456 focuses on tumors with this precise genetic vulnerability, potentially sparing healthy cells and reducing side effects. Abemaciclib, known for inhibiting cancer cell growth, when combined with TNG456, could enhance the treatment's effectiveness against certain stubborn cancers like non-small cell lung cancer (NSCLC) and glioblastoma (GBM). This targeted approach might provide new hope for patients who have limited options with existing therapies.

What evidence suggests that this trial's treatments could be effective for solid tumors with MTAP loss?

Research has shown that TNG456, a drug under study in this trial, might help treat advanced or spreading solid tumors with a specific genetic change called MTAP loss. This change is common in several cancers and may make tumors more sensitive to TNG456. Early results suggest that TNG456 could work by stopping cancer cells from growing.

In this trial, some participants will receive TNG456 alone, while others will receive it in combination with abemaciclib, a drug already used for cancer. This combination is being specifically tested for non-small cell lung cancer and glioblastoma, a type of brain cancer. Early studies of similar drug combinations have shown promising results in slowing tumor growth in various solid tumors. This combination aims to more effectively stop cancer cells from dividing and growing. ^{1 2 3 4 6}

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, including lung cancer and glioblastoma, that have MTAP loss. Participants must be able to swallow tablets, have adequate organ function, measurable disease progression after standard care or no available standard therapy. Pregnant individuals can't join.

Inclusion Criteria

I can swallow pills.

Negative serum pregnancy test result at screening

I am fully active or can carry out light work.

Exclusion Criteria

Has a prior or ongoing clinically significant illness that may affect the safety of the patient, impair the assessment of study results or compliance with the protocol

I have been treated with a PRMT5 or MAT2A inhibitor before.

I am currently pregnant or breastfeeding.

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 TNG456 as a single agent and in combination with abemaciclib to estimate the maximum tolerated dose

3 weeks

Dose Expansion

Participants receive TNG456 at the recommended phase 2 dose (RP2D) as a single agent or in combination with abemaciclib, depending on tumor type

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• abemaciclib
• TNG456

Trial Overview The study tests TNG456 alone and combined with abemaciclib in patients whose tumors lack MTAP. It's a first-in-human study with two parts: dose escalation to find the safe amount and dose expansion to see effects on specific tumor types.

How Is the Trial Designed?

Group I: Tumor Agnostic Single Agent Dose Expansion Experimental Treatment 1 Intervention

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

Group II: Tumor Agnostic Combination Expansion Experimental Treatment 2 Interventions

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

Group III: Single Agent and Combination Dose Escalation Experimental Treatment 2 Interventions

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

Group IV: NSCLC Single Agent Dose Expansion Experimental Treatment 1 Intervention

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

Group V: NSCLC Combination Expansion Experimental Treatment 2 Interventions

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

Group VI: GBM Single Agent Dose Expansion Experimental Treatment 1 Intervention

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

Group VII: GBM Combination Expansion Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Tango Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

740+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[2022]

Abemaciclib, an oral CDK4 and CDK6 inhibitor, was evaluated in a study with 225 patients, showing a maximum tolerated dose of 200 mg every 12 hours and a safety profile that allows for continuous dosing, with fatigue being the most common side effect.

The drug demonstrated significant antitumor activity, particularly in hormone receptor-positive breast cancer, achieving a 31% overall response rate and 61% of patients experiencing either a response or stable disease for at least 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Patnaik, A., Rosen, LS., Tolaney, SM., et al.[2022]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

First-generation precision medicine trials like NCI-MATCH have successfully demonstrated the feasibility of large-scale studies on targeted therapies in oncology, but single-agent therapies have had limited success in controlling metastatic cancer.

To improve outcomes, newer second-generation trials such as ComboMATCH, iMATCH, and myeloMATCH are being developed to explore combinations of targeted therapies and standard treatments, addressing the limitations of previous approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New NCI Precision Medicine Trials. Harris, LN., Blanke, CD., Erba, HP., et al.[2023]

In co-clinical trials using patient-derived xenograft models, the multikinase inhibitor dovitinib showed significant tumor regression in some lung squamous cell carcinoma (LSCC) models (PDX-01 and PDX-05), while others (PDX-02, PDX-03, and PDX-04) exhibited tumor progression, indicating variable efficacy based on tumor characteristics.

Gene expression profiles revealed that activation of the FGFR signaling pathway is a critical predictor of sensitivity to dovitinib, suggesting that FGFR gene expression signatures could be used to identify patients who are more likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Kim, HR., Kang, HN., Shim, HS., et al.[2022]

In the neoMONARCH study, postmenopausal women with HR+/HER2- breast cancer showed significant decreases in Ki67 expression and achieved higher rates of complete cell-cycle arrest when treated with abemaciclib alone or in combination with anastrozole compared to anastrozole alone.

The combination therapy not only inhibited cancer cell growth but also enhanced immune activation, suggesting a dual mechanism of action that could improve treatment outcomes, while the most common side effects were manageable gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. Hurvitz, SA., Martin, M., Press, MF., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06810544

NCT06810544 | Safety and Tolerability of TNG456 Alone ... This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP ...

2. dana-farber.org dana-farber.org/clinical-trials/25-177

A Phase 1/2, Multicenter, Open-Label Study to Evaluate the ... This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an MTAP ...

3. trials.braintumor.org trials.braintumor.org/trials/NCT06810544

Safety and Tolerability of TNG456 Alone and in Combination ... 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 ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/573495

Safety and Tolerability of TNG456 Alone and in ... This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors ...

5. ir.tangotx.com ir.tangotx.com/news-releases/news-release-details/tango-therapeutics-reports-second-quarter-2025-financial-results

Tango Therapeutics Reports Second Quarter 2025 Financial ... The study is evaluating the pharmacokinetics, pharmacodynamics, safety and efficacy of TNG260 in combination with pembrolizumab in patients with ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-02619

Safety and Tolerability of TNG456 Alone and in ... This is a first in human study of TNG456 alone and in combination with abemaciclib in patients with advanced or metastatic solid tumors known to have an ...