vopimetostat (TNG462) / Tango Therap - LARVOL DELTA

TNG462-C101: Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors (clinicaltrials.gov) - P1/2 | N=225 | Recruiting | Sponsor: Tango Therapeutics, Inc. | Trial completion date: Sep 2026 ➔ Jun 2028 | Trial primary completion date: May 2026 ➔ Jun 2027

First-in-human • Trial completion date • Trial primary completion date • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • MTAP

A Phase 1/2 study of vopimetostat in combination with daraxonrasib or zoldonrasib in patients with MTAP deleted RAS mutated (MTAPdel/RASmut) metastatic PDAC and NSCLC (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP • RAS

Tango Therapeutics...Provides Business Highlights (GlobeNewswire) - "Present Phase 1/2 data of vopimetostat in combination with RAS(ON) inhibitors at the 2026 ESMO Congress in Madrid, Spain from October 23-27, 2026; Finalize design of Phase 3 randomized-controlled trial of the combination approach in front-line pancreatic cancer in 2H 2026; Disclose vopimetostat lung cancer monotherapy data in 2H 2026; Release initial TNG456 data in glioblastoma and other cancers in 2H 2026; Initiate Phase 1/2 vopimetostat + ERAS-0015 (Erasca) combination study in 2H 2026."

Clinical protocol • New P1/2 trial • P1/2 data • Glioblastoma • Pancreatic Cancer

Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients (clinicaltrials.gov) - P1/2 | N=133 | Recruiting | Sponsor: Tango Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

Vopimetostat plus daraxonrasib combination: As of a data cutoff date of May 28, 2026, 59 patients with previously treated MTAP-deleted and RAS-mutant pancreatic ductal adenocarcinoma (PDAC) or non-small cell lung cancer (NSCLC) were treated with a vopimetostat-based combination with...daraxonrasib (n=20 PDAC; n=5 NSCLC) (Yahoo Finance) - "PDAC: 92% objective response rate (ORR) (11/12; 9 of 11 responses confirmed); 90% 6-month PFS rate; 100% disease control rate (DCR); NSCLC: 100% ORR, 3 of 3 responses confirmed; The vopimetostat + daraxonrasib was generally well tolerated across all dose levels with no new safety signals observed...There were no related Grade 4 or 5 adverse events....Based on these data, Tango intends to rapidly advance this combination approach into Phase 3 development for patients with MTAP-deleted pancreatic cancer."

New P3 trial • P1/2 data • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Upcoming Anticipated Milestones (Yahoo Finance) - "Finalize design of Phase 3 randomized-controlled trial of the combination approach in front-line pancreatic cancer in 2H 2026; Disclose vopimetostat lung cancer monotherapy data in 2H 2026; Release initial TNG456 glioblastoma data 2H 2026; Present 2/3L PDAC vopimetostat + RAS(ON) inhibitors combination data at a scientific conference 2H 2026; Initiate Phase 1/2 vopimetostat + ERAS-0015 combination study 2H 2026."

Clinical protocol • New P1/2 trial • New P3 trial • P1/2 data • Glioblastoma • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Vopimetostat plus zoldonrasib combination (PDAC with MTAP deletion and KRAS G12D mutation) (Yahoo Finance) - "Data highlights include: 52% ORR (14/27; 10 of 14 responses confirmed); 74% 6-month PFS rate; 96% DCR; The vopimetostat plus zoldonrasib combination was generally well tolerated at all dose levels with no new safety signals observed; Most adverse events were Grade 1 or 2. The most common TRAEs were nausea and vomiting; There were no related Grade 4 or 5 adverse events."

P1/2 data • Pancreatic Ductal Adenocarcinoma

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov) - P1/2 | N=60 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | N=342 ➔ 60 | Trial completion date: Oct 2031 ➔ May 2027 | Trial primary completion date: Oct 2031 ➔ May 2027 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • MTAP

Tango Therapeutics…Provides Business Highlights (GlobeNewswire) - "Upcoming Expected Milestones: (i) Initial phase 1/2 safety and efficacy data from combination trial with vopimetostat + daraxonrasib, and vopimetostat + zoldonrasib (Revolution Medicines) in 2026; (ii) Vopimetostat monotherapy phase 1/2 clinical data lung cancer update in 2026; (iii) TNG456 monotherapy phase 1/2 trial initial safety and efficacy data in 2026' (iv) Initiate phase 1/2 vopimetostat + ERAS-0015 (Erasca) combination study 2H 2026."

New P1/2 trial • P1/2 data • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov) - P1/2 | N=342 | Recruiting | Sponsor: Servier Bio-Innovation LLC | Active, not recruiting ➔ Recruiting | N=104 ➔ 342

Enrollment change • Enrollment open • First-in-human • Esophageal Cancer • Gastric Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • MTAP

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov) - P1/2 | N=104 | Active, not recruiting | Sponsor: Servier Bio-Innovation LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Esophageal Cancer • Gastric Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • MTAP

MTAP loss alters the epigenetic landscape and demonstrates superior therapeutic sensitivity to concomitant PRMT5 and PARP inhibition in cholangiocarcinoma (AACR 2024) - P1 | "This renders selective targeting of MTAP null tumors with agents (MRTX1719, AMG193, TNG462, TNG908) targeting MTA bound PRMT5 (PRMT5:MTA), while sparing surrounding normal MTAP wild-type (WT) tissue...To address this pressing need, we co-treated CCA cell lines with MRTX1719 and PARP inhibitor olaparib...Similar differences in proportion of splicing events were also observed in MTAP loss CCA patient derived xenografts as compared to WT models. Collectively, these data implicate MTAP to be a crucial player in modulation of the chromatin and splicing events that may drive therapeutic response to PRMT5 inhibition."

Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors with MTAP loss (AACR 2025) - "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 are clinical-stage MTA-cooperative PRMT5 inhibitors for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant. Oral administration of TNG456 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in multiple cell line- and patient-derived xenograft models. With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including gliomas and CNS metastases."

Brain Cancer • CNS Tumor • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

Tango Therapeutics Announces Leadership Appointments to Accelerate Late-Stage Development of Vopimetostat (GlobeNewswire) - "'We look forward to presenting key clinical data this year, including initial data from our combination trial with Revolution Medicines, Inc.’s RAS(ON) inhibitors'."

Clinical data • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Genome-wide drug anchor screens identify CAAP1 and AKAP17A as regulators of PRMT5 inhibitor sensitivity (AACR 2024) - "CAAP1 or AKAP17A knockout in MTAP-deleted cancer cell lines sensitized the cells to PRMT5 inhibitors including the clinical stage MTA-cooperative inhibitors, TNG908 and TNG462, and the non-MTA-cooperative inhibitor, GSK3326595. S. Yoda and M. R. Tonini contributed equally."

Oncology • CAAP1 • CDKN2A • MTAP

Evaluation of the impact of homozygous MTAP truncations on the clinical activity of MTA-cooperative PRMT5 inhibitors (AACR 2025) - "To benefit this large patient population, MTA-cooperative PRMT5 inhibitors, including TNG908, TNG462, and TNG456 were developed to leverage the synthetic lethal relationship between MTAP deletion and PRMT5 inhibition. Previously, we reported that homozygous loss of only the terminal exon (exon 8), an event reported to occur in only 0.5% of MTAP-deleted tumors, is insufficient for complete loss of MTAP activity in preclinical assays. Here, we report initial evidence for the clinical impact of MTAP truncations, as opposed to complete deletion, on the activity of MTA-cooperative PRMT5 inhibitors."

Clinical • Oncology • CDKN2A • MTAP

TNG462, an MTA-cooperative PRMT5 inhibitor, demonstrates strong efficacy in combination with clinically relevant targeted therapies in MTAP-null preclinical models (AACR 2025) - "This supports our clinical development plans for TNG462, which include targeted combinations with two RAS(ON) inhibitors, RMC-6236 and RMC-9805 from Revolution Medicines, as well as the EGFR inhibitor osimertinib from AstraZeneca...Significant efficacy was observed in preclinical models with the combination of TNG462 and CDK4/6 inhibitors, supporting a potential development path in GBM for our next generation CNS penetrant PRMT5 inhibitor, TNG456, with abemaciclib...However, TNG462 monotherapy at a clinically relevant dose achieved comparable benefits to the combination. Collectively, these findings strongly support evaluating TNG462 in combination with other targeted therapies in clinical trials for patients with cancers that exhibit MTAP loss."

Combination therapy • Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDKN2A • KRAS • MAT2A • MTAP

Evaluation of the impact of homozygous MTAP truncations on the activity and selectivity of MTA-cooperative PRMT5 inhibitors (AACR 2024) - P1/2 | "To benefit this large and diverse patient population, MTA-cooperative PRMT5 inhibitors, including TNG908 and TNG462, have been developed to leverage the synthetic lethal relationship between MTAP deletion and PRMT5 inhibition. Here, we present our initial functional genomics analysis of this important diagnostic biomarker using in vitro cDNA reconstitution approaches for MTAP activity combined with analysis of PRMT5 inhibitor sensitivity. Ultimately, these data may help refine patient enrollment on clinical trials to drive the maximum benefit for patients with MTAP-deleted cancers."

Oncology • CDKN2A • MTAP

Upcoming Expected Milestones (GlobeNewswire) - "(i) Initial phase 1/2 safety and efficacy data from combination trial with vopimetostat + daraxonrasib, and vopimetostat + zoldonrasib (Revolution Medicines) in 2026; (ii) Vopimetostat monotherapy phase 1/2 clinical data lung cancer update in 2026; (iii) Vopimetostat monotherapy 2L pancreatic cancer pivotal study start in 2026; (iv) TNG456 monotherapy phase 1/2 trial initial safety and efficacy data in 2026."

New trial • P1/2 data • Glioblastoma • Glioma • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Erasca and Tango Therapeutics Enter into Clinical Collaboration to Evaluate Combination of ERAS-0015 and Vopimetostat (GlobeNewswire) - "This agreement will support a Phase 1/2 clinical trial evaluating ERAS-0015 in combination with vopimetostat in patients with MTAPdel pancreatic or MTAPdel RASm non-small cell lung cancer (NSCLC). Erasca will supply ERAS-0015 free of charge, and Tango will be the trial sponsor."

Commercial • New P1/2 trial • Non Small Cell Lung Cancer

CL1-95035-001: A study of S095035 as a single agent and in combination in adult participants with advanced or metastatic solid tumors with deletion of MTAP (clinicaltrialsregister.eu) - P1/2 | N=118 | Recruiting | Sponsor: Institut De Recherches Internationales Servier IRIS

New P1/2 trial • Esophageal Cancer • Gastric Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients (clinicaltrials.gov) - P1/2 | N=183 | Recruiting | Sponsor: Tango Therapeutics, Inc. | N=133 ➔ 183

Enrollment change • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (SNO 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

MTA-Cooperative PRMT5 Inhibitors Demonstrate Efficacy in MTAP-Deleted MPNST Models and Enhance Chemotherapy Response (SNO 2025) - "Furthermore, the combination of a PRMT5 inhibitor with doxorubicin or trabectedin had additive antiproliferative effects. In vivo, TNG908 and TNG462 demonstrated dose-dependent antitumor activity in MTAP-null MPNST PDX models WU-356 and WU-386, inducing tumor regressions at well-tolerated doses.CONCLUSIONTNG908 and TNG462 selectively inhibited MTAP-deleted MPNST cell growth in vitro and induced tumor regressions in vivo through PRMT5 inhibition and apoptosis induction. These findings support the therapeutic potential of MTA-cooperative PRMT5 inhibitors as a targeted treatment strategy for patients with MTAP-deleted MPNST."

Clinical • Brain Cancer • Neurofibrosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CASP3 • CDKN2A • MTAP

MTA-Cooperative PRMT5 Inhibitors Demonstrate Efficacy in MTAP-Deleted MPNST Models and Enhance Chemotherapy Response (WFNOS 2025) - "Furthermore, the combination of a PRMT5 inhibitor with doxorubicin or trabectedin had additive antiproliferative effects. In vivo, TNG908 and TNG462 demonstrated dose-dependent antitumor activity in MTAP-null MPNST PDX models WU-356 and WU-386, inducing tumor regressions at well-tolerated doses.CONCLUSIONTNG908 and TNG462 selectively inhibited MTAP-deleted MPNST cell growth in vitro and induced tumor regressions in vivo through PRMT5 inhibition and apoptosis induction. These findings support the therapeutic potential of MTA-cooperative PRMT5 inhibitors as a targeted treatment strategy for patients with MTAP-deleted MPNST."

Clinical • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • CASP3 • CDKN2A • MTAP