Clinical trial NCT06922591: Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients
Official title: A Phase 1/2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability & Antitumor Activity of TNG462 in Combination With Other Agents in Patients With Pancreatic or Non-Small Cell Lung Cancer With MTAP Loss & RAS Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: PDAC
PDAC - Pancreatic Ductal Adenocarcinoma
NSCLC
RAS Mutation
MTAP Deletion
Lung Cancer
Pancreatic Cancer Metastatic
Thoracic Cancer
Keywords: PRMT5 inhibitor
RAS G12D
Multi RAS
RMC-9805
RMC-6236
Thoracic
Targeted therapy
Lead sponsor: Tango Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Revolution Medicines, Inc.
First posted: 2025-04-10
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation of TNG462 + RMC-9805 and TNG462 + RMC-6236 followed by expansion of each combination in MTAP loss and RAS mutant PDAC and NSCLC
Primary purpose: TREATMENT

Brief summary: TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236 or RMC-9805. The study comprises a dose escalation phase and a dose expansion phase.

Detailed description: TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236 or RMC-9805.

The study will be conducted in patients with MTAP loss and RAS mutant metastatic pancreatic adenocarcinoma (PDAC) or locally advanced or metastatic non-small cell lung cancer (NSCLC) in 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion).

Individual Arms in the dose expansion phase may open once the MTD and/or RD(s) has been determined for the corresponding combination in the dose escalation phase of the study.

Eligibility criteria: Inclusion Criteria:

1. Is ≥18 years of age at the time of signature of the main study ICF.
2. Has an ECOG PS of 0 or 1.
3. Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene
4. Has a tumor with a RAS mutation
5. Pathologically documented metastatic PDAC or locally advanced, recurrent or metastatic NSCLC
6. Has received prior standard therapy
7. Must not have received prior RAS-targeted therapy
8. Has evidence of measurable disease based on RECIST v1.1.
9. Adequate organ function
10. Must be able to swallow tablets.
11. Negative pregnancy test at screening
12. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor
2. Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805
3. Known allergy, hypersensitivity or intolerance to TNG462, RMC-6236, RMC-9805 or their excipients
4. Has uncontrolled intercurrent illness that will limit compliance with the study requirements.
5. Has an active infection requiring systemic therapy.
6. Is currently participating in or has planned concurrent participation in a study of another investigational agent or device.
7. Has impairment of GI function or disease that may significantly alter the absorption of the oral medications
8. Has known or suspected active or untreated CNS metastases associated with progressive neurological symptoms
9. Has current active liver disease from any cause
10. Is known to be HIV positive, unless all the following criteria are met:

    1. CD4+ count ≥300/µL.
    2. Undetectable viral load.
    3. Receiving highly active antiretroviral therapy
11. Has clinically relevant cardiovascular disease
12. History of or presence of active interstitial lung disease
13. Is a female patient who is pregnant or lactating
14. Is unwilling or unable to comply with the scheduled visits, study treatment administration plan, laboratory tests or other study procedures and study restrictions.
15. 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 ability to assess study results

Primary outcomes:
measure: Phase 1: Maximum Tolerated Dose
timeFrame: 21 days
measure: Phase 2: Combination Anti-neoplastic Activity
timeFrame: 9 weeks
Secondary outcomes:
measure: Phase 1: Combination Anti-neoplastic Activity
timeFrame: 9 weeks
measure: Phase 1 and 2: Cmax of TNG462 and in Combination
timeFrame: 21 days
measure: Phase 1 and 2: Tmax of TNG462 and in Combination
timeFrame: 21 days
measure: Phase 1 and 2: AUC of TNG462 and in Combination
timeFrame: 21 days
measure: Phase 1 and 2 Adverse Event Profile
timeFrame: 21 days
Other outcomes:
Locations:
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
Study officials:
affiliation: Tango Therapeutics, Inc.
name: Maeve Waldron-Lynch, MD
role: STUDY_DIRECTOR
References: