(P 558) TRIAL IN PROGRESS: A PHASE 1/2 STUDY OF BRIGATINIB IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH ALK POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA OR INFLAMMATORY MYOFIBROBLASTIC TUMORS (ITCC-098)

Objective: Brigatinib is a second generation orally administered anaplastic lymphoma kinase (ALK) inhibitor, approved by FDA and EMA for the treatment of adult patients with ALK positive (ALK+) non-small cell lung cancer. In this population, brigatinib showed a superior efficacy, tolerability, and central nervous system penetration at the recommended phase two dose of 180 mg once daily (qd) after a 7-day lead-in at 90 mg qd, compared to the first generation ALK inhibitor crizotinib. The most common ALK driven tumors in the pediatric and adolescent population are anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMT). IMTs are rare solid tumors which are primarily treated with surgical resection. There is currently no standard of care approach for systemic treatment in case of relapsed/refractory (R/R) disease, or at primary diagnosis in case of metastasized or unresectable tumors, including if surgery is expected to be mutilating. The aim of this study is to assess the safety, efficacy, and pharmacokinetics of brigatinib monotherapy in children and adolescents with ALK+ ALCL and IMT.

Methods: The BrigaPED study is a non-randomized, open-label, multicenter, phase 1/2 trial of brigatinib in the context of a pediatric investigation plan (NCT04925609). In phase 1, brigatinib is evaluated in up to 3 dose levels according to the rolling six design. Brigatinib is orally administered once daily in 28-day cycles, with a maximum of 24 cycles. A 7-day lead-in phase was introduced before the start of cycle 1 to minimize the risk of early pulmonary toxicity based on prior experience in adults. Dose limiting toxicities (DLTs) are evaluated in the first 35 days of treatment, including the 7-day lead-in phase and the first cycle. The RP2D will be based on DLTs and pharmacokinetic data. Adverse events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Written informed consent and adequate organ function are required for study eligibility.

The primary objective for phase 1 is to establish the recommended phase 2 dose (RP2D) of brigatinib monotherapy in children. Eligible patients for phase 1 are patients aged 1-18 years with: 1) newly diagnosed unresectable or metastatic, or R/R ALK+ IMT, 2) R/R ALK+ ALCL, including patients with persistent positive qualitative measurable residual disease (MRD) during frontline treatment, or 3) other ALK+ solid tumors. In phase 2 we will evaluate the efficacy of brigatinib monotherapy in patients aged ≥ 1 and < 26 years, with newly diagnosed unresectable or metastatic, or R/R ALK+ IMT (cohort B1, n = 28), or R/R ALK+ ALCL including patients with persistent positive qualitative MRD during frontline treatment (cohort B2, n = 22).

A total of 36 sites in 16 countries across Europe and Israel are planned to be opened, of which the first opened in March 2022. To date, 8 patients were included in phase 1.

Results: Not applicable

Conclusion: Not applicable