Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TNG462 · 2 trials · 9 indications
To determine the MTD and RD(s) of TNG462 in combination with RMC-6236 or RMC-9805
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
To determine the maximum tolerated dose (MTD) of TNG462 when administered as a single agent and in combination with pembrolizumab
To determine the dosing schedule of TNG462
To assess anti-neoplastic activity of TNG462 administered single agent and in combination with pembrolizumab in patients with MTAP-deleted advanced solid tumors by RECIST v1.1, iRECIST or mRECIST v1.1
| Arm | Type | Description |
|---|---|---|
| Dose Escalation 1A | EXPERIMENTAL | Escalating oral doses of TNG462 in combination with oral RMC-6236 |
| Dose escalation 1B | EXPERIMENTAL | Escalating oral doses of TNG462 in combination with oral RMC-9805 |
| Dose Expansion 2A | EXPERIMENTAL | Expansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236 |
| Dose Expansion 2B | EXPERIMENTAL | Expansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805 |
| Experimental: Dose Escalation 1C | EXPERIMENTAL | Escalating doses of TNG462 in combination with mFOLFIRINOX |
| Experimental: Dose Escalation 1D | EXPERIMENTAL | Escalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel |
| Experimental: Dose Expansion 2C | EXPERIMENTAL | Expansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX |
| Experimental: Dose Expansion 2D | EXPERIMENTAL | Expansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel |
| Dose Escalation | EXPERIMENTAL | Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 single agent and in combination with pembrolizumab to estimate the MTD |
| Dose Expansion in NSCLC | EXPERIMENTAL | Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s) |
| Dose Expansion in Mesothelioma | EXPERIMENTAL | Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s) |
| Dose Expansion in Pancreatic Ductal Adenocarcinoma | EXPERIMENTAL | Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s) |
| Dose Expansion in Sarcoma | EXPERIMENTAL | Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s) |
| Dose Expansion in Solid Tumors | EXPERIMENTAL | Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s) |
| Dose Expansion in NSCLC in Combination with Pembrolizumab | EXPERIMENTAL | Participants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s) |
| Name | Type | Description |
|---|---|---|
| TNG462 | DRUG | MTA cooperative PRMT5 inhibitor |
| RMC-9805 | DRUG | RAS(ON) G12D selective covalent inhibitor |
| RMC-6236 | DRUG | RAS(ON) multi-selective inhibitor |
| mFOLFIRINOX | DRUG | Chemotherapy |
| gemcitabine/nab-paclitaxel | DRUG | Chemotherapy |
| Pembrolizumab | DRUG | An anti PD-1 antibody, will be administered intravenously |
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...