Erasca has entered two clinical trial collaboration and supply agreements with Novartis to support the development of mitogen-activated protein kinase kinase (MEK) inhibitor trametinib in combination with naporafenib for cancer.
The trials, SEACRAFT-1 and SEACRAFT-2, aim to treat patients with rat sarcoma (RAS) Q61X solid tumours and previously treated NRAS-mutant melanoma, respectively.
SEACRAFT-1 is a Phase Ib trial which will assess the combination of naporafenib and trametinib in patients with RAS Q61X solid tumours.
The Phase III randomised SEACRAFT-2 trial is enrolling subjects with NRAS-mutant unresectable or metastatic melanoma.
The studies are sponsored by Erasca while Novartis will provide trametinib at no cost for the trial.
Naporafenib is a pan-RAF inhibitor, which demonstrated potential as both a first-in-class and best-in-class treatment option.
It has been dosed in more than 500 patients so far, demonstrating tolerability, safety, and pharmacokinetic and pharmacodynamic profiles as a single agent and combination therapy.
Clinical proof-of-concept (PoC) was proven for use along with trametinib for neuroblastoma rat sarcoma (NRAS)-mutant melanoma, including NRAS Q61X melanoma.
Preliminary clinical PoC has also been established for the combination regimen in non-small cell lung cancer.
Erasca's immediate focus is on advancing naporafenib plus trametinib through regulatory approval processes for NRAS-mutant melanoma in the SEACRAFT-2 trial and for RAS Q61X tissue agnostic solid tumours in the SEACRAFT-1 trial.
Furthermore, the company is investigating additional combinations with other therapeutic agents in its pipeline.
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 III trial in the first half of 2024 and report initial SEACRAFT-1 Phase Ib combination data in RAS Q61X solid tumours between the second and fourth quarters of 2024.”
