PDAC, PDAC - Pancreatic Ductal Adenocarcinoma, NSCLC, RAS Mutation, MTAP Deletion, Lung Cancer, Pancreatic Cancer Metastatic, Thoracic Cancer
Conditions
Keywords
PRMT5 inhibitor, RAS G12D, Multi RAS, RMC-9805, RMC-6236, Thoracic, Targeted therapy
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, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. 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, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. For the RAS inhibitor arms, 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). For the chemotherapy specific arms, the study will be conducted in patients with MTAP loss locally advanced or metastatic PDAC. The entire study (all arms) will be conducted 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.
Interventions
Sponsors
Revolution Medicines, Inc.
Tango Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation of TNG462 + RMC-9805, TNG462 + RMC-6236, TNG462 + mFOLFIRINOX and TNG462 + gemcitabine/nab-paclitaxel, followed by expansion of each combination in MTAP loss and RAS mutant PDAC and NSCLC
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. Arms A and B only: 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. Arms A and B only: 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. Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or RMC-9805 3. Known allergy, hypersensitivity or intolerance to TNG462 (all arms), RMC-6236 Arm A), RMC-9805 (Arm B), mFOLFIRINOX (Arm C), gemcitabine/nab-paclitaxel (Arm D) 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Maximum Tolerated Dose | 21 days | To determine the MTD and RD(s) of TNG462 in combination with RMC-6236 or RMC-9805 |
| Phase 2: Combination Anti-neoplastic Activity | 12 weeks | To assess preliminary evidence of antineoplastic activity of TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel using RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and 2: Cmax of TNG462 and in Combination | 21 days | To characterize the Cmax of TNG462 in combination with RMC-6236 or RMC-9805 |
| Phase 1: Combination Anti-neoplastic Activity | 12 weeks | To assess preliminary evidence of antineoplastic activity of TNG462 in combination with RMC-6236, RMC-9805, mFOLFIRINOX, or gemcitabine/nab paclitaxel using RECIST 1.1 |
| Phase 1 and 2 Adverse Event Profile | 21 days | To determine the safety and tolerability of TNG462 in combination with RMC-6236 or RMC-9805 |
| Phase 1 and 2: AUC of TNG462 and in Combination | 21 days | To characterize the AUC of TNG462 and in combination with RMC-6236 or RMC-9805 |
| Phase 1 and 2: Tmax of TNG462 and in Combination | 21 days | To characterize the Tmax of TNG462 in combination with RMC-6236 or RMC-9805 |
Countries
United States
Contacts
Primary ContactMaxim Pimpkin, MD, PhD
Outcome results
None listed