Tovorafenib has been granted accelerated approval by the FDA for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma

April 2024: The Food and Drug Administration (FDA) granted accelerated approval to tovorafenib (Ojemda, Day One Biopharmaceuticals, Inc.). This approval is specifically for patients aged 6 months and older who have relapsed or refractory pediatric low-grade glioma (LGG) and have either a BRAF fusion or rearrangement, or a BRAF V600 mutation.

This marks the initial approval by the FDA of a systemic treatment for patients with juvenile low-grade glioma (LGG) who have BRAF rearrangements, including fusions.

Safety and efficacy of tovorafenib

The effectiveness of the treatment was assessed in 76 patients who participated in the FIREFLY-1 (NCT04775485) trial. This trial was conducted at multiple centers and involved patients with relapsed or refractory pediatric LGG. A nearby laboratory found that these patients had a specific genetic change in the BRAF gene. Additionally, all patients had previously received at least one form of systemic therapy.

Patients were mandated to possess documented proof of radiographic advancement and a minimum of one quantifiable lesion. Patients with tumors that had other genetic problems that made them more likely to grow, like IDH1/2 mutations or FGFR mutations, or who knew or thought they might have neurofibromatosis type 1 were not included in the study.

Patients were administered tovorafenib at a dosage based on their body surface area, ranging from 290 to 476 mg/m2, with a maximum dose of 600 mg. The medication was given once a week until patients either reported disease progression or intolerable toxicity.

The overall response rate (ORR) was the main way to measure how well the treatment worked. The ORR shows what percentage of patients had a full response (CR), a partial response (PR), or a minor response (MR) based on the RAPNO-LGG criteria for Response Assessment in Pediatric Neuro-Oncology for Low-Grade Glioma.

A blinded independent central review (BICR) conducted the assessment. Other effectiveness criteria considered were the length of time that the response to treatment lasted (DoR). The objective response rate (ORR) was 51%, with a 95% confidence interval (CI) ranging from 40% to 63%. The median duration of response (DoR) was 13.8 months, with a 95% CI ranging from 11.3 months to not estimable.

The predominant side effects (≥30%) included rash, alterations in hair color, exhaustion, viral infection, vomiting, headache, bleeding, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.

The most prevalent laboratory abnormalities in Grade 3 or 4 (>2%) were reduced phosphate levels, reduced hemoglobin levels, elevated creatinine phosphokinase levels, elevated alanine aminotransferase levels, reduced albumin levels, reduced lymphocyte count, reduced leukocyte count, elevated aspartate aminotransferase levels, reduced potassium levels, and reduced sodium levels.

According to body surface area (BSA), 380 mg/m2 taken orally once a week is the recommended dosage of tovorafenib. The maximum recommended dosage is 600 mg taken orally once a week. It can be taken with or without food until there is disease progression or the patient experiences severe toxicity.

Tovorafenib is offered in the form of either an instant release tablet or an oral suspension. No proven suggested dosage exists for patients with a body surface area (BSA) less than 0.3 m2.

Susan Hau

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Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.

Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.

Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.

Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.

These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.

Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.

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• June 19th, 2024