Clinical Trials

FIREFLY-1 is a pivotal Phase 2, multicenter open-label study designed to evaluate the safety and efficacy of tovorafenib in patients aged 6 months to 25 years with relapsed or progressive low-grade glioma or solid tumors harboring a known activating BRAF alteration. The low-grade glioma arms have completed enrollment. Results from the low-grade glioma registrational arm 1 ‘The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial’ were published in Nature Medicine in 2024.

Additional information about FIREFLY-1 may be found at ClinicalTrials.gov, using identifier NCT04775485.

FIREFLY-2 is a pivotal Phase 3, randomized, multicenter open-label trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy, an investigational, oral, RAF inhibitor versus standard of care (SoC) chemotherapy in patients with RAF-altered pediatric low-grade glioma requiring front-line systemic therapy. The primary endpoint will be overall response rate (ORR) based upon Response Assessment for Neuro-Oncology (RANO) criteria. Secondary endpoints include progression-free survival (PFS) by independent review committee (IRC) per RANO-LGG, duration of response (DOR) assessed by IRC per RANO-LGG, and overall survival.

Additional information about the FIREFLY-2 trial may be found at ClinicalTrials.gov, using identifier NCT05566795.

FIRELIGHT-1 is a multi-center, open-label umbrella master trial designed to evaluate the safety and efficacy of tovorafenib in patients with recurrent or progressive solid tumors with activating RAF alterations. This trial will accrue adolescents 12 years and above and adults. The Phase 1b/2 substudy (102b) evaluating the combination of tovorafenib with the Company’s investigational MEK inhibitor, pimarsertib, is currently enrolling patients with recurrent or progressive melanoma or other solid tumors with alterations in the key proteins of the MAPK pathway. Tovorafenib will be evaluated alone or combined with pimasertib. The Phase 1b trial will evaluate the safety of the combination and select the dose for the Phase 2 trial. The Phase 2 trial will evaluate anti-tumor activity. The primary endpoint will be overall response rate (ORR) as assessed by RECIST version 1.1 criteria. Secondary and exploratory endpoints include safety, duration of response, progression-free survival, and time to response.

Additional information about FIRELIGHT-1 may be found at ClinicalTrials.gov, using identifier NCT04985604.