Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
- Conditions
- Non Small Cell Lung CancerGlioma Glioblastoma MultiformeGlioma, MalignantSolid TumorNon-Small Cell AdenocarcinomaLung CancerBrain Tumor
- Interventions
- Registration Number
- NCT06810544
- Lead Sponsor
- Tango Therapeutics, Inc.
- Brief Summary
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.
- Detailed Description
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 escalation study of oral TNG456 administered as a single agent and in combination with oral abemaciclib in solid tumor patients with confirmed MTAP loss. In the Phase 2 expansion part of the study, 6 arms defined by confirmed tumor types will enroll in parallel at the RP2D(s) of TNG456 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 191
- Has a tumor with a confirmed MTAP loss
- Is ≥18 years of age at the time of signature of the main study ICF
- Has had progression or an inadequate response to or is intolerant of the approved standard of care therapy, no standard of care therapy exists, or the investigator has determined that treatment with the standard of care therapy is not appropriate.
- Is able to swallow tablets
- Adequate Organ function/reserve per local labs
- Negative serum pregnancy test result at screening
- Has an ECOG performance status score of 0 to 1
- Has measurable disease based on RECIST v1.1 or a confirmed glioblastoma (IDH-wildtype) with radiographic evidence of disease progression or recurrence defined by RANO 2.0.
- Has an ECOG performance score of 0 to 1 or for GBM has a Karnofsky performance status score ≥70.
- A female patient is who is pregnant or breastfeeding
- Has impaired GI function or disease that may significantly alter the absorption of oral study treatment(s)
- Has an active infection requiring systemic therapy
- Has received prior treatment with a PRMT5 inhibitor or a MAT2A inhibitor
- Patients in the expansion receiving the combination therapy that have received prior treatment with a CDK4/6 inhibitor
- Clinically relevant cardiovascular disease
- Has a prior or ongoing clinically significant illness may affect the safety of the patient, impair the assessment of study results or compliance with the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Single Agent and Combination Dose Escalation abemaciclib Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD NSCLC Combination Expansion abemaciclib NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib GBM Combination Expansion abemaciclib GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Tumor Agnostic Combination Expansion abemaciclib Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Single Agent and Combination Dose Escalation TNG456 Solid tumor participants with confirmed MTAP loss will receive escalating doses of TNG456 single agent and in combination with abemaciclib to estimate the MTD NSCLC Single Agent Dose Expansion TNG456 NSCLC (squamous and non squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) GBM Single Agent Dose Expansion TNG456 GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) Tumor Agnostic Single Agent Dose Expansion TNG456 Patients with specific solid tumor types that have a confirmed MTAP loss will receive TNG456 at the identified RP2D(s) NSCLC Combination Expansion TNG456 NSCLC (squamous and non-squamous) participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib GBM Combination Expansion TNG456 GBM participants with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib Tumor Agnostic Combination Expansion TNG456 Participants with specific tumor types with confirmed MTAP loss will receive TNG456 at the identified RP2D(s) with abemaciclib
- Primary Outcome Measures
Name Time Method Phase 1 Maximum Tolerated Dose 21 days To determine the MTD, recommended dose(s) (RD), and dosing schedule of TNG456 monotherapy and in combination with abemaciclib
Phase 2 Anti-neoplastic Activity Single Agent 18 weeks To assess the antitumor activity of TNG456 in patients with advanced or metastatic solid tumors with MTAP loss by RECIST or modified RANO criteria
Phase 2 Anti-neoplastic Activity Combination Treatment 18 weeks To assess the antitumor activity of TNG456 in combination with abemaciclib in patients with advanced or metastatic tumors with MTAP loss by RECIST or modified RANO criteria
- Secondary Outcome Measures
Name Time Method Phase 1 Anti-neoplastic Activity Single Agent 18 weeks To assess preliminary evidence of antitumor activity of TNG456 in patients with advanced solid tumors with MTAP loss by RECIST or modified RANO criteria
Phase 1 and 2 Adverse Event Profile 21 days To describe the safety and tolerability profile of TNG456 as a monotherapy and in combination with abemaciclib
Phase 1 and 2 Concentration versus Time Curve 16 days Measure the area under the plasma concentration versus time curve (AUC)
Phase 1 and 2 Time to Achieve Maximal Plasma Concentration 16 days Measure the time to achieve maximal plasma concentration (Tmax)
Phase 1 and 2 Maximum Observed Plasma Concentration 16 days Measure the maximum observed plasma concentration (Cmax)
Related Research Topics
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Trial Locations
- Locations (2)
NYU Langone Health
🇺🇸New York, New York, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States