Day One Biopharmaceuticals announced positive early data assessing tovorafenib as a once-a-week treatment in people aged six months to 25 years with relapsed or progressive pediatric low-grade glioma.
South San Francisco-based Day One Biopharmaceuticals announced positive early data from the first 22 evaluable patients in its Phase II FIREFLY-1 trial. The study is assessing tovorafenib as a once-a-week treatment in people aged six months to 25 years with relapsed or progressive pediatric low-grade glioma (pLGG).
pLGG is the most commonly diagnosed brain tumor in children. There are no approved therapies and no standard of care. It makes up 30% to 50% of all CNS tumors. BRAF wild-type fusions are the most common genetic alterations seen in these types of cancer, although they are also found in several adult and pediatric solid tumors.
Most children with pLGG survive the cancer. But children who do not achieve remission after surgery often face years of increasingly aggressive therapies that can affect learning, cognition and quality of life.
The primary endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria assessed by a blinded independent central review. The initial data on the first 25 RANO-evaluable patients demonstrated a 64% ORR and 91% CBR, which is partial response/unconfirmed partial response plus stable disease in the 22 RANO-evaluable patients. There were 14 partial responses, 13 confirmed and one unconfirmed. Six patients had stable disease. All of the patients with stable disease were seen to have tumor shrinkage that varied from 19% to 43%.
The responses were seen in patients with both BRAF fusions and BRAF V600E mutations who received previous MAPK-targeted therapy. The median-time-to-response was 2.8 months. The side effects were manageable because nobody discontinued treatment because of them.
“These initial findings underscore the potential of tovorafenib monotherapy to become a significant and transformative new option for relapsed/progressive pLGG, a pediatric brain tumor with no approved treatments today,” Dr. Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer of Day One said. “With the registrational cohort fully enrolled, patient follow-up is ongoing, and we look forward to the topline data from the complete study population in the first quarter of 2023. Based on these positive initial data, we plan to begin the pivotal Phase III FIREFLY-2 clinical trial evaluating tovorafenib as a front-line therapy in pLGG to evaluate whether tovorafenib can provide benefit early in the disease development.”
Tovorafenib is an oral, brain-penetrant, highly selective type II pan-RAF kinase inhibitor. It targets a key enzyme in the MAPK signaling pathway. It is being evaluated as a monotherapy or in combination with other drugs for adolescents and adults with recurrent or progressive solid tumors with MAPK pathway aberrations. The drug has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the U.S. Food and Drug Administration for patients with pLGG harboring an activating RAF alteration. It also received Orphan Drug designation from the FDA for malignant glioma and from the European Commission (EC) for glioma.
Based on the data from FIREFLY-1, the company plans to expand the drug’s development as a front-line therapy for newly diagnosed pLGG patients. FIREFLY-2/LOGGIC is a Phase III trial that will study once-weekly monotherapy tovorafenib in this patient subset.
“These initial data demonstrate significant anti-tumor activity in children with relapsed/progressive pLGG, including children who are refractory to available therapies,” Dr. Roger Packer, M.D., senior vice president, Center for Neuroscience and Behavioral Medicine and director, Brain Tumor Institute, Children’s National Hospital said. “Pediatric low-grade glioma is a truly challenging disease in which children face years of aggressive regimens that can carry a long-term impact on learning, cognition, and quality of life.”
Some investors have shown concern over the company’s rate of cash usage (cash burn), but at least one analyst believes it has a “solid cash runway” and the current good news puts it on strong footing should it need to raise more money. Day One Bio has a market cap of $962 million. Last year it went through $60 million in cash, which is only 6.5% of its market value, meaning “it would probably be really easy for the company to fund another year’s growth by issuing some new shares to investors, or even by taking out a loan.”
Company shares popped at the trial news, up a whopping 85.66% during premarket trading on Monday.
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