Novel Therapy Being Assessed for the Treatment of RAF-Altered Solid Tumors

The first patient with a recurrent or progressive solid tumor with an activating RAF alteration has been dosed in a phase 1b/2 multi-center clinical trial assessing the effects of DAY101 as a monotherapy treatment for patients who have these tumors, according to Day One Biopharmaceuticals, the manufacturer of the agent.

DAY101 is an oral brain-penetrating drug. Previous studies have shown its benefit in patients with brain tumors or brain metastases.

“DAY101 has demonstrated encouraging anti-tumor activity as a monotherapy in patient populations where MAPK pathway alterations are believed to play an important role in driving disease progression,” said Dr. Samuel Blackman, co-founder and chief medical officer of Day One, in a news release.

The phase 2 portion of the study, FIRELIGHT-1, is anticipated to analyze the efficacy and safety of DAY101 in combination with pimasertib, an MEK inhibitor. The plan is to administer the drug to 43 adult and adolescent patients aged 12 years and older, who are enrolled in either a melanoma or “tissue agnostic” patient group. The researchers expect to be finished assessing for the main outcome by July 2025.

Patients may be eligible for FIRELIGHT-1 if they are between the ages of six months to 25 years, have a relapsed or progressive low-grade glioma with a known activating BRAF alteration, have received at least one line of systemic therapy and have evidence of radiographic progression and have at least one measurable lesion.

For the phase 1b portion – FIREFLY-1, which researchers expect to initiate in early 2022, pediatric, adolescent and young adult patients with recurrent or progressive low-grade glioma (pLGG) with a BRAF alteration are expected to receive the combination therapy. It is estimated that the main focus of the trial should be completed by March 2023. Researchers plan to dose 60 patients in this study.

Patients could potentially qualify for participation in FIREFLY-1 if they are aged 12 years and older, with informed parental consent for those who are minors. They also must have a confirmed diagnosis of non-hematologic tumor with an activating BRAF fusion, CRAF/RAF1 fusion or CRAF/RAF1 amplification; radiographically-recurrent or radiographically-progressive disease; archival tumor tissue or fresh tumor tissue and previously treated/stable brain metastases (if they are present).

The Food and Drug Administration (FDA) recently granted DAY101 a breakthrough therapy designation for the treatment of patients with pLGG who have an RAF alteration, require systemic therapy and whose disease progressed after previous treatment with no other satisfactory options. A breakthrough therapy designation means that the FDA may expedite the review of the drug.

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