Clinical trial NCT06810544: Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
Official title: A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Glioma Glioblastoma Multiforme
Glioma, Malignant
Solid Tumor
Non-Small Cell Adenocarcinoma
Lung Cancer
Brain Tumor
Keywords: MTAP
PRMT5 inhibitor
CDK 4/6
abemaciclib
Tango
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2025-02-05
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 dose escalation (sequential) followed by phase 2 dose expansion (parallel)
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Phase 1 Maximum Tolerated Dose
timeFrame: 21 days
measure: Phase 2 Anti-neoplastic Activity Single Agent
timeFrame: 18 weeks
measure: Phase 2 Anti-neoplastic Activity Combination Treatment
timeFrame: 18 weeks
Secondary outcomes:
measure: Phase 1 Anti-neoplastic Activity Single Agent
timeFrame: 18 weeks
measure: Phase 1 and 2 Adverse Event Profile
timeFrame: 21 days
measure: Phase 1 and 2 Concentration versus Time Curve
timeFrame: 16 days
measure: Phase 1 and 2 Time to Achieve Maximal Plasma Concentration
timeFrame: 16 days
measure: Phase 1 and 2 Maximum Observed Plasma Concentration
timeFrame: 16 days
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Maeve Waldron-Lynch, MD
role: STUDY_DIRECTOR
References: