FDA Approves Ibrutinib for Previously Treated Peds and Young Adults With cGVHD

The FDA has granted approval to ibrutinib (Imbruvica) for the treatment of pediatric patients ≥ 1 year of age with chronic graft versus host disease (cGVHD) who failed 1 or more lines of systemic therapy. Ibrutinib is available for this indication as a capsule, tablet, and oral suspension.¹

Approval was granted based on findings from the phase ½ IMAGINE clinical trial (NCT03790332). The study showed activity through a positive objective response rate and response durability.

In 47 pediatric patients with cGVHD, the ORR at week 25 was 60% (95% CI: 44-74). The median duration of response observed was 5.3 months (95% CI: 2.8- 8.8). The study also showed a median time from first response to death or new systemic therapies for cGVHD of 14.8 months (95% CI: 4.6 to not evaluable).¹

For safety, the most common adverse events were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache. Common AEs occurred in ≥ 20% of patients in the study.

IMAGINE was an open-label, multi-center, single-arm trial of ibrutinib administered to pediatric and young adult patients with moderate or severe cGVHD. Baseline characteristics showed that patients had a median age of 13 years (range, 1-19). The population was 70% male, 36% White, 9% Black or African American, and 55% other or unreported.²

In the IMAGINE trial, patients with moderate to severe cGVHD aged 1-22 with a Karnofsky or Lansky performance score of ≥ 60 are treated with ibrutinib 120 mg/m2 once daily during phase 1, which is escalated to 240 mg/m2 after 14 days in patients without grade 3 toxicity to determine the recommended phase 2 dose of the agent. The coprimary end points of the study are PK, and safety/tolerability determined by the number of patients with AEs. As secondary end points, the study is investigating safety/tolerability, response rate at week 24, duration of response, overall survival, late effects surveillance, and laboratory parameters.²

According to the FDA, the recommended dosage of ibrutinib for patients 12 years of age and older with cGVHD is 420 mg orally once daily. For patients who are 1 year old to younger than 12 years old with cGVHD, the recommended dosage is 240 mg/m2 orally once daily. Ibrutinib can be administered until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.¹

“The pediatric cGVHD community is a prime example of an underserved patient population with high unmet medical needs for whom Janssen is committed to developing life-saving therapies,” said Craig Tendler, MD, global head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology Janssen Research & Development, LLC, in a press release.³ “cGVHD has life-threatening implications for children, and we are deeply proud of the opportunity to make an impact for these young patients with Imbruvica and their families.”

_REFERENCES:

_{1. FDA approves ibrutinib for pediatric patients with chronic graft versus host disease, including a new oral suspension. News release. FDA webstie. Accessed August 24, 2022. https://bit.ly/3CoNsMy}

_{2. Phase 1/2 dose finding and safety study of ibrutinib in pediatric subjects with chronic graft versus host disease (cGVHD). Clinicaltrials.gov. Accessed February 28, 2022. https://bit.ly/3K9GfAJ}

_{3. U.S. FDA approves Imbruvica® (ibrutinib) as first and only BTKi treatment for pediatric patients with chronic graft-versus-host disease. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. August 24, 2022. Accessed August 24, 2022. https://bit.ly/3QWiLms}