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TNG462

Phase 1

Locally Advanced Solid Tumor | Small molecule | Oncology |Tango Therapeutics, Inc.|Last Updated: Sep 8, 2026

Target and mechanism

Molecular targetPRMT5
Target classProtein
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment225

FDA Designations

FAST_TRACKORPHAN_DRUG

Clinical trial landscape

TNG462 · 2 trials · 9 indications

Phase 1 2
NCT06922591Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC PatientsPDAC
RECRUITING183 Analytics
NCT05732831Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid TumorsLocally Advanced Solid Tumor
RECRUITING225 Analytics
PHASE1RECRUITING
Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients
PDACUnlock trial analytics
PHASE1RECRUITING
Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors
Locally Advanced Solid TumorUnlock trial analytics

Study Endpoints

Primary Endpoints

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

Phase 1 Maximum Tolerated Dose
28 days and 21 days

To determine the maximum tolerated dose (MTD) of TNG462 when administered as a single agent and in combination with pembrolizumab

Phase 1 Dosing Schedule
28 days

To determine the dosing schedule of TNG462

Phase 2 Anti-neoplastic Activity
16 weeks and 18 weeks

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

Secondary Endpoints

Phase 1: Combination Anti-neoplastic Activity
12 weeks
Phase 1 and 2: Tmax of TNG462 and in Combination
21 days
Phase 1 and 2: Cmax of TNG462 and in Combination
21 days
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Dose Escalation 1AEXPERIMENTALEscalating oral doses of TNG462 in combination with oral RMC-6236
Dose escalation 1BEXPERIMENTALEscalating oral doses of TNG462 in combination with oral RMC-9805
Dose Expansion 2AEXPERIMENTALExpansion arm at the RDE(s) of oral TNG462 in combination with oral RMC-6236
Dose Expansion 2BEXPERIMENTALExpansion arm at the RDE(s) of oral TNG462 in combination with oralRMC-9805
Experimental: Dose Escalation 1CEXPERIMENTALEscalating doses of TNG462 in combination with mFOLFIRINOX
Experimental: Dose Escalation 1DEXPERIMENTALEscalating doses of TNG462 in combination with gemcitabine/nab-paclitaxel
Experimental: Dose Expansion 2CEXPERIMENTALExpansion arm at the RDE(s) of TNG462 in combination with mFOLFIRINOX
Experimental: Dose Expansion 2DEXPERIMENTALExpansion arm at the RDE(s) of TNG462 in combination with gemcitabine/nab-paclitaxel
Dose EscalationEXPERIMENTALParticipants 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 NSCLCEXPERIMENTALParticipants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s)
Dose Expansion in MesotheliomaEXPERIMENTALParticipants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s)
Dose Expansion in Pancreatic Ductal AdenocarcinomaEXPERIMENTALParticipants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s)
Dose Expansion in SarcomaEXPERIMENTALParticipants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s)
Dose Expansion in Solid TumorsEXPERIMENTALParticipants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)
Dose Expansion in NSCLC in Combination with PembrolizumabEXPERIMENTALParticipants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s)

Interventions

NameTypeDescription
TNG462DRUGMTA cooperative PRMT5 inhibitor
RMC-9805DRUGRAS(ON) G12D selective covalent inhibitor
RMC-6236DRUGRAS(ON) multi-selective inhibitor
mFOLFIRINOXDRUGChemotherapy
gemcitabine/nab-paclitaxelDRUGChemotherapy
PembrolizumabDRUGAn anti PD-1 antibody, will be administered intravenously
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites18

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...

Countries:United StatesFranceSpain
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Recent Changes (Last 90 Days)

MEDIUMSep 8, 2026NCT05732831primaryCompletionDate: changed
MEDIUMSep 8, 2026NCT05732831primaryCompletionDate: changed

Frequently asked questions about TNG462

What is TNG462 used for?

TNG462 is an investigational small molecule being developed for oncology indications, including locally advanced solid tumors and pancreatic ductal adenocarcinoma (PDAC). It is being studied in patients with MTAP-deleted solid tumors and in combination regimens for PDAC and non-small cell lung cancer (NSCLC) with RAS mutations and MTAP deletions.

What does TNG462 target?

TNG462 targets PRMT5, a protein methyltransferase involved in cellular processes relevant to cancer. By inhibiting PRMT5, TNG462 is being evaluated as a potential treatment for tumors with MTAP deletions, which are common in certain cancers such as pancreatic ductal adenocarcinoma and non-small cell lung cancer.

Who is developing TNG462?

TNG462 is being developed by Tango Therapeutics, Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol TNGX. The company is conducting clinical trials to evaluate the safety, tolerability, and efficacy of TNG462 in patients with specific solid tumor types.

What phase is TNG462 in?

TNG462 is in Phase 1 clinical development. It is an investigational drug that has not yet been approved by regulatory authorities. The ongoing Phase 1 trials are recruiting patients to assess the safety, tolerability, and preliminary efficacy of TNG462 as a monotherapy and in combination with other agents.

What clinical trials is TNG462 in?

TNG462 is being studied in two Phase 1 clinical trials. NCT05732831 evaluates TNG462 monotherapy in patients with MTAP-deleted solid tumors across the United States, France, and Spain. NCT06922591 evaluates TNG462 in combination for PDAC and NSCLC patients with RAS mutations and MTAP deletions in the United States.

Is TNG462 the same as any other drug?

TNG462 is a distinct investigational compound developed by Tango Therapeutics. It is not known to be the same as any other marketed drug. Its unique mechanism of targeting PRMT5 in MTAP-deleted tumors differentiates it from other cancer therapies currently in development.