Tango Therapeutics has initiated a Phase 1/2 trial evaluating TNG462, a PRMT5 inhibitor, in combination with Revolution Medicines’ RAS inhibitors (daraxonrasib and zoldonrasib) for patients with MTAP-deleted, RAS-mutant metastatic pancreatic or lung cancer. Preclinical data indicates strong synergistic activity between TNG462 and the RAS inhibitors, and previous clinical trials have shown these individual molecules to be well-tolerated and effective in these cancer types. This trial (NCT06922591) will assess the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of the combination therapies.
This trial holds significant promise for advancing cancer treatment, particularly for pancreatic and lung cancer patients with MTAP deletions and RAS mutations. These co-occurring genetic alterations are prevalent in these cancers, creating a substantial unmet medical need. The combination therapy approach directly targets these vulnerabilities, offering the potential for a more effective treatment strategy compared to existing options. Positive results could transform the treatment landscape for these patient populations.
The Phase 1/2 trial is designed to collect crucial data on the combination therapies’ safety and effectiveness. Tango Therapeutics also expects data from its ongoing Phase 1/2 monotherapy trial of TNG462 in the latter half of 2025. This monotherapy data will inform a potential registrational trial for pancreatic cancer in the following year and further guide the development plan for lung cancer.
The initiation of this combination therapy trial represents a critical step forward in the development of precision oncology treatments. Positive clinical outcomes could establish TNG462, in combination with RAS inhibitors, as a crucial component in the treatment paradigm for MTAP-deleted, RAS-mutant cancers, potentially leading to improved patient outcomes and potentially expanding treatment options for these challenging cancer types.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
