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OJEMDA (tovorafenib) logo: 100 mg tablets 25 mg/mL for oral suspension

For US healthcare professionals only

Study Design

FIREFLY-1 Design

The largest clinical trial in BRAF-altered R/R pLGG to date1,2

137 patients received OJEMDA in the pivotal FIREFLY-1 trial3

FIREFLY-1 is a global, open-label, nonrandomized, multicenter, phase 2 trial.1,3

Key Inclusion Criteria3

  • 6 months - 25 years old
  • BRAF-altered R/R pLGG
  • At least 1 prior systemic therapy with documented radiographic progression

Key Exclusion Criteria3

Patients with:

  • Tumors harboring additional activating alterations (eg, IDH1/2 mutations, FGFR mutations, etc.)
  • Known or suspected diagnosis of NF1

OJEMDA 420 mg/m2 once weekly (max 600 mg)1,3*

Primary Efficacy Analysis (N=76)1

  • Arm 1† (registrational arm)
  • Median duration of treatment was 15.8 months (0.7-23.7 months)3

Primary Safety Analysis (N=137)1

  • Arm 1 + Arm 2‡ (registrational and extension arms)
  • Median duration of treatment was 12 months (0.7-23.7 months)4

Major Outcomes

Major efficacy outcome3§

  • ORR (RAPNO-LGG criteria)‖

Select secondary outcomes3

  • CBR
  • Time to response
  • Duration of response

Safety outcome4

  • Safety and tolerability
  • FIREFLY-1 concluded its investigational period in 20243
  • The last patient from Arm 1 reached 2 years on therapy in the second quarter of 20244
  • Long-term follow-up is ongoing for patients continuing therapy or on drug holiday4
  • *Patients received OJEMDA approximately 420 mg/m2 orally once weekly (range: 290 to 476 mg/m2, 0.76-1.25 times the approved recommended dosage) according to BSA with a maximum dosage of 600 mg until disease progression or unacceptable toxicity.1
  • †77 patients were enrolled in Arm 1; 76 patients were considered evaluable for response by RAPNO-LGG criteria.1,3
  • ‡Arm 2 is an extension arm, which provided treatment access for patients with BRAF-altered pLGG after the registrational arm closure.3
  • §The primary endpoint was the ORR according to RANO-HGG criteria.3
  • IIORR was defined as the proportion of patients with CR, PR, or MR by independent review based on RAPNO-LGG criteria.1
  • CBR defined as proportion of patients with best overall response of confirmed CR, PR, MR, or SD lasting 12 months or more based on RAPNO criteria.3

In FIREFLY-1, OJEMDA delivered clinically meaningful tumor shrinkage.1

See the results

Baseline Characteristics

Baseline characteristics from FIREFLY-1, reflective of patients seen in clinical practice5

OJEMDA was studied in a patient population for whom multiple lines of prior therapies failed3

Baseline Characteristics (N=76)1,3

Age (Years)

Median (range)

8.5 (2-21)

Sex

Male

53%

Female

47%

BRAF alterations

BRAF fusion

74%

V600E mutation

16%

Other (including BRAF duplication or rearrangement)

11%

Number of prior
systemic regimens

Median (range)

3 (1-9)

1

22%

2

27%

≥3

51%

Prior MAPK-targeted therapy

No

41%

Yes

59%

Common Tumor Locations1

Cerebral hemisphere

0%

Optic pathway

0%

Cerebellum

0%

Brain
stem

0%

Deep midline structures

0%

BRAF=v-Raf murine sarcoma viral oncogene homolog B1; BSA=body surface area; CBR=clinical benefit rate; CR=complete response; FGFR=fibroblast growth factor receptor; IDH=isocitrate dehydrogenase; MAPK=mitogen-activated protein kinase; MR=minor response; NF1=neurofibromatosis type 1; ORR=overall response rate; PR=partial response; RANO-HGG=Response Assessment for Neuro-Oncology High-Grade Glioma; RAPNO-LGG=Response Assessment in Pediatric Neuro-Oncology for Low-Grade Glioma; R/R pLGG=relapsed/refractory pediatric low-grade glioma; SD=stable disease.

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Discover clinically meaningful responses

Discover the efficacy data

References

  • 1. OJEMDA™ [Package Insert]. Brisbane, CA: Day One Biopharmaceuticals, Inc.; 2024.
  • 2. Bouffet E, Hansford JR, Garrè ML, et al. Dabrafenib plus trametinib in pediatric glioma with BRAF V600 mutations. N Engl J Med. 2023;389(12):1108-1120. doi:10.1056/NEJMoa2303815
  • 3. Kilburn LB, Khuong-Quang DA, Hansford JR, et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024;30(1):207-217. doi:10.1038/s41591-023-02668-y
  • 4. Data on file. Day One Biopharmaceuticals, Inc.
  • 5. Ryall S, Zapotocky M, Fukuoka K, et al. Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas. Cancer Cell. 2020;37(4):569-583.e5. doi:10.1016/j.ccell.2020.03.011

IMPORTANT SAFETY INFORMATION and INDICATION

Warnings and Precautions

Hemorrhage

Hemorrhage, including major hemorrhage defined as symptomatic bleeding in a critical area or organ, can occur with OJEMDA. Advise patients and caregivers of the risk of hemorrhage during treatment with OJEMDA. Monitor for signs and symptoms of hemorrhage and evaluate as clinically indicated. Withhold and resume at reduced dose upon improvement, or permanently discontinue based on severity.

Skin Toxicity Including Photosensitivity

OJEMDA can cause rash, including maculopapular rash and photosensitivity. Monitor for new or worsening skin reactions. Consider dermatologic consultation and initiate supportive care as clinically indicated. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction.

Photosensitivity

Advise patients to use precautionary measures against ultraviolet exposure such as use of sunscreen, sunglasses, and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose, or permanently discontinue OJEMDA based on severity of adverse reaction.

Hepatotoxicity

OJEMDA can cause hepatotoxicity. Monitor liver function tests, including ALT, AST and bilirubin, before initiation of OJEMDA, one month after initiation and then every three months thereafter and as clinically indicated. Withhold and resume at the same or reduced dose upon improvement, or permanently discontinue OJEMDA based on the severity.

Effect on Growth

OJEMDA can cause reductions in growth velocity. Growth velocity recovered after interruption of treatment with OJEMDA. Routinely monitor patient growth during treatment with OJEMDA.

Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, OJEMDA may cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Advise females of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 28 days after the last dose, since OJEMDA can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective nonhormonal contraception during treatment with OJEMDA and for 2 weeks after the last dose.

NF1 Associated Tumors

Based on nonclinical data in NF1 models without BRAF alterations, tovorafenib may promote tumor growth in patients with NF1 tumors. Confirm evidence of a BRAF alteration prior to initiation of treatment with OJEMDA.

Adverse Reactions

The most common adverse reactions (≥30%) were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.

Please see full Prescribing Information.

Indication

OJEMDATM (tovorafenib) is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.

This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).