Tango Therapeutics (TNGX) Study result summary

Study background and rationale

• Vopimetostat, an oral PRMT5 inhibitor, was evaluated in combination with pan-RAS inhibitors (daraxonrasib and zoldonrasib) in MTAP-deleted, RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC), targeting a highly challenging malignancy.

• Over 90% of pancreatic cancers harbor RAS mutations, making RAS inhibition a promising therapeutic strategy.

• Preclinical and clinical studies demonstrated synergy between PRMT5 and RAS inhibition, supporting clinical investigation and maximal synergy with panRAS inhibitors.

• The study included heavily pre-treated patients with MTAP loss, mostly with prior chemotherapy, and assessed both efficacy and safety.

• The combination approach aims to provide a chemotherapy-free regimen for first-line pancreatic cancer treatment and patients with limited alternatives.

Study design and patient population

• Ongoing Phase 1/2 trial enrolled 59 patients: 20 PDAC and 5 NSCLC received vopimetostat plus daraxonrasib; 34 PDAC received vopimetostat plus zoldonrasib.

• Patients were heavily pre-treated, with over half receiving the combinations as third-line therapy.

• Nearly all MTAP-deleted PDAC patients have co-occurring KRAS mutations, highlighting a large, high-need target population.

• MTAP-deleted cancers represent 10-15% of all cancers and 40% of pancreatic cancers.

• Approximately 60,000 patients in the US have MTAP-deleted metastatic cancers annually, with PDAC representing a significant portion.

Key clinical results / Efficacy results

• Vopimetostat plus daraxonrasib in PDAC showed a 92% objective response rate (ORR), 90% six-month progression-free survival (PFS), and 100% disease control rate (DCR) in heavily pretreated patients.

• Vopimetostat plus zoldonrasib in PDAC achieved a 52% ORR, 74% six-month PFS, and 96% DCR in KRAS G12D-mutant patients.

• Combined ORR in 2/3L PDAC was 64%, with a combined DCR of 97%.

• Responses were observed in both second- and third-line settings, with no meaningful difference in efficacy between these groups.

• The combination also showed high activity in MTAP-deleted NSCLC, with a 93-100% ORR in a small cohort.