The collaboration is focused on evaluating MEK inhibitor trametinib in combination with pan-RAF inhibitor naporafenib in SEACRAFT-1 and SEACRAFT-2 clinical trials, where Erasca will sponsor the clinical trials and Novartis will supply trametinib at no cost
Novartis will supply trametinib for Erasca clinical trials at no-cost. (Credit: Novartis AG)
US-based clinical-stage precision oncology company Erasca has signed two clinical trial collaboration and supply agreements (CTCSAs) with Swiss pharmaceutical form Novartis.
The collaboration is focused on evaluating MEK inhibitor trametinib in combination with pan-RAF inhibitor naporafenib in SEACRAFT-1 and SEACRAFT-2 clinical trials.
Erasca will sponsor the clinical trials and Novartis will supply trametinib at no cost.
The Phase 1b SEACRAFT-1 trial will evaluate naporafenib in combination with trametinib for the treatment of patients with RAS Q61X solid tumours.
The Phase 3 SEACRAFT-2 trial will evaluate the combination in patients with previously treated NRAS-mutant (NRASm) unresectable or metastatic melanoma.
Erasca chairman, CEO, and co-founder Jonathan Lim said: “We are excited to work with Novartis to further evaluate the promising clinical development of naporafenib in combination with trametinib in our SEACRAFT trials as part of our two lead indications: NRASm melanoma and RAS Q61X solid tumours.
“Both trials are supported by compelling anti-tumour activity with a tolerable and manageable adverse event profile demonstrated in clinical data generated by Novartis. We expect to initiate our SEACRAFT-2 Phase 3 trial in the first half of 2024 and report initial SEACRAFT-1 Phase 1b combination data in RAS Q61X solid tumours between the second and fourth quarters of 2024.”
Naporafenib, previously known as LXH254, is a potent and selective pan-RAF inhibitor with a potential first-in-class and best-in-class profile.
The drug has been dosed in more than 500 patients to date, establishing safety, tolerability, pharmacokinetics, and pharmacodynamics.
The clinical proof-of-concept (PoC) has been established for the naporafenib plus trametinib combination for patients with NRAS-mutant (NRASm) melanoma and patients with RAS Q61X in non-small cell lung cancer (NSCLC).
Erasca will initially focus on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the planned Phase 3 SEACRAFT-2 trial.
The company will also seek regulatory approval for the combination in RAS Q61X tissue agnostic solid tumours as part of the Phase 1b SEACRAFT-1 trial.
Naporafenib has received FDA Fast Track Designation for patients with metastatic NRASm melanoma who are intolerant to an anti-PD(L) -1-based regimen.
Furthermore, Erasca is exploring whether naporafenib plus trametinib combination can improve outcomes and provide meaningful therapeutic benefits for advanced solid tumour indications.