Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TNG462 · 3 trials · 10 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
Phase 1 only
Phase 1 only
Phase 1 only
Phase 2 only; Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 criteria as per the investigator's assessment and by blinded independent central review (BICR)
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 |
| Phase 1 Arm 1 - S095035 single-agent dose escalation | EXPERIMENTAL | - |
| Phase 1 Arm 2 - S095035-TNG462 combination dose escalation | EXPERIMENTAL | - |
| Phase 2 Arm 1a NSCLC - S095035 single-agent dose expansion | EXPERIMENTAL | Non-Small Cell Lung Cancer |
| Phase 2 Arm 1b BTC - S095035 single-agent dose expansion | EXPERIMENTAL | Biliary Tract Cancer |
| Phase 2 Arm 1c PDAC - S095035 single-agent dose expansion | EXPERIMENTAL | Pancreatic Ductal Adenocarcinoma |
| Phase 2 Arm 1d Basket arm - S095035 single-agent dose expansion | EXPERIMENTAL | - |
| Phase 2 Arm 2a BTC - S095035-TNG462 combination dose expansion | EXPERIMENTAL | Biliary Tract Cancer |
| Phase 2 Arm 2b Gastroesophageal - S095035-TNG462 combination dose expansion | EXPERIMENTAL | - |
| Phase 2 Arm 2c PDAC - S095035-TNG462 combination dose expansion | EXPERIMENTAL | Pancreatic Ductal Adenocarcinoma |
| 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 |
| S095035 | DRUG | S095035 will be taken orally every day in 28-day cycles. |
| 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...
TNG462 is an investigational small molecule being studied for locally advanced or metastatic solid tumors, particularly cancers with MTAP deletion. It is also being evaluated in pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) in combination with other agents. It has not been approved for any indication.
TNG462 targets PRMT5, a protein arginine methyltransferase. By inhibiting PRMT5, TNG462 is designed to exploit the vulnerability of cancer cells with MTAP deletion, which are more sensitive to PRMT5 inhibition. This targeted approach is being tested in biomarker-selected solid tumors.
TNG462 is being developed by Tango Therapeutics, Inc., a biotechnology company focused on precision oncology. Tango Therapeutics trades on the Nasdaq under the ticker symbol TNGX.
TNG462 is in Phase 1 clinical development. It is currently being evaluated in early-stage trials to assess safety, tolerability, and preliminary efficacy in patients with advanced solid tumors, including MTAP-deleted cancers and pancreatic ductal adenocarcinoma.
TNG462 is being studied in three Phase 1 trials: NCT06922591 in PDAC and NSCLC, NCT06188702 in MTAP-deleted solid tumors, and NCT05732831 in locally advanced solid tumors. All are actively recruiting or ongoing, with a combined enrollment of approximately 225 patients.
Yes, TNG462 has received Fast Track designation from the FDA. This designation is intended to expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. TNG462 remains investigational and has not been approved.