Tango Therapeutics, Inc. announced that the first patient has been dosed in its Phase 1/2 trial evaluating TNG462 in combination with Revolution Medicines’ daraxonrasib or zoldonrasib. This trial targets patients with MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer, addressing a significant unmet medical need in these difficult-to-treat cancers. Preclinical data have shown strong combination activity between TNG462 and both daraxonrasib and zoldonrasib.
Almost all MTAP-deleted pancreatic cancers and approximately 30% of lung cancers have a co-occurring RAS mutation, indicating a substantial patient population that could benefit from this combination therapy. TNG462 is an MTA-cooperative PRMT5 inhibitor, and its combination with RAS(ON) inhibitors aims to exploit multiple genetic vulnerabilities in cancer cells. Single-agent clinical data for these molecules have demonstrated tolerability and activity in pancreatic and lung cancer.
The Phase 1/2 combination trial (NCT06922591) is designed to assess the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of TNG462 in combination with each of Revolution Medicines' inhibitors. An upcoming monotherapy data update for TNG462, expected in the second half of 2025, is anticipated to provide information to guide a registrational trial in pancreatic cancer in 2026 and further advance the development plan for lung cancer.
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