191 Participants Needed

TNG456 + Abemaciclib for Solid Tumors

Recruiting at 1 trial location
MW
Overseen ByMaeve Waldron-Lynch, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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 loss. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific solid tumor types with a confirmed MTAP loss. The study drug, TNG456, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 191 participants.

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.

What data supports the effectiveness of the drug combination TNG456 and Abemaciclib for solid tumors?

The research highlights the use of precision medicine in oncology, where treatments are tailored based on the tumor's molecular profile, suggesting that targeted therapies like TNG456 and Abemaciclib could be more effective for specific patient groups. Additionally, the success of precision medicine trials in identifying effective drug combinations supports the potential of this approach.12345

What safety data exists for abemaciclib in humans?

Abemaciclib has been studied for safety in humans, showing that the most common side effects include fatigue and issues with the stomach, kidneys, or blood. The highest safe dose was found to be 200 mg every 12 hours, with severe tiredness being the main dose-limiting problem.678910

What makes the drug TNG456 + Abemaciclib unique for treating solid tumors?

The combination of TNG456 and Abemaciclib is unique because Abemaciclib is a CDK4/6 inhibitor that has shown effectiveness in various cancers by blocking proteins that help cancer cells grow. This combination may offer a novel approach by potentially enhancing the immune response against tumors, which is different from standard treatments that typically target cancer cells directly.678911

Research Team

MW

Maeve Waldron-Lynch, MD

Principal Investigator

Tango Therapeutics, Inc.

Eligibility Criteria

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.
See 5 more

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.
See 4 more

Timeline

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

Treatment Details

Interventions

  • abemaciclib
  • TNG456
Trial OverviewThe 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.
Participant Groups
7Treatment groups
Experimental Treatment
Group I: Tumor Agnostic Single Agent Dose ExpansionExperimental Treatment1 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 ExpansionExperimental Treatment2 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 EscalationExperimental Treatment2 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 ExpansionExperimental Treatment1 Intervention
NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
Group V: NSCLC Combination ExpansionExperimental Treatment2 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 ExpansionExperimental Treatment1 Intervention
GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s)
Group VII: GBM Combination ExpansionExperimental Treatment2 Interventions
GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib

Find a Clinic Near You

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 profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

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

References

New clinical trial designs in the era of precision medicine: An overview of definitions, strengths, weaknesses, and current use in oncology. [2022]
Emerging precision neoadjuvant systemic therapy for patients with resectable non-small cell lung cancer: current status and perspectives. [2023]
Precision oncology based on omics data: The NCT Heidelberg experience. [2022]
Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. [2022]
The New NCI Precision Medicine Trials. [2023]
CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer. [2019]
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. [2022]
Pharmacokinetic study on the co-administration of abemaciclib and astragaloside IV in rats. [2022]
Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer. [2023]
An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]