Phase 1:

• To determine the MTD/RP2D regimen of brigatinib monotherapy when administered in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors, including ALK+ IMT.
•  To characterize the PK of brigatinib administered as monotherapy in pediatric and AYA patients with ALK+ ALCL or ALK+ solid tumors, including ALK+ IMT.

Note that:
o If the MTD is not reached at the highest proposed test dose, no further dose-escalation will be performed.
o Pediatric PK data, compared to exposure in adults, will be taken into consideration to determine the RP2D.

Phase 2:

• Cohort B1, ALK+ IMT:
  To establish the anti-tumor activity of single agent brigatinib when administered to children with ALK+ IMT.
• Cohort B2, ALK+ ALCL:
  To establish the efficacy of single agent brigatinib when administered to children with ALK+ ALCL for a
  duration of 2 years, without planned HSCT in consolidation.

Phase 1:

• To assess the safety and tolerability of brigatinib administered as monotherapy in pediatric and AYA patients during course 1, as well as the cumulative toxicities in patients receiving multiple courses of brigatinib.
• To assess the acceptability and palatability of brigatinib.
• To describe long term toxicity (toxicity during the off-therapy period up to 5 years after study inclusion), with special attention to ocular, pulmonary, endocrine adverse events and height, weight or growth abnormalities.
• To describe the anti-tumor activity and survival estimates of brigatinib as monotherapy in pediatric and AYA population.
• To assess the cumulative incidence of non-response or relapse on treatment and during follow-up.
• To describe the outcome for ALCL patients with and without SCT, after a remission induced with brigatinib.
• To describe anti-tumor activity for ALCL patients that are re-challenged with brigatinib for a relapse occurring after brigatinib discontinuation.
• To describe histological response in resected specimens from IMT patients undergoing surgery after brigatinib treatment.
• To describe on treatment survival, taking into account reasons for study discontinuation such as toxicity or switch to alternative treatments.

Phase 2:

 Safety (in both cohorts)

• To assess the safety and tolerability of brigatinib administered as monotherapy in pediatric and AYA patients
•  To assess the cumulative toxicities in patients receiving multiple courses of brigatinib, including endocrine and ophthalmologic toxicities.
• To describe long term toxicity (toxicity during the off-therapy period up to 5 years after study inclusion) with special attention to ocular, pulmonary, endocrine adverse events and height, weight or growth abnormalities.
• To assess the acceptability and palatability of brigatinib.
• To collect plasma concentration-time data for brigatinib and construct a population PK model, and to relate exposure to safety parameters.
• To describe the cumulative incidence of non-relapse mortality.

Efficacy/activity
In Cohort B1, ALK+ IMT:

• To estimate the activity of brigatinib in terms of:
  o time to best response,
  o duration of response (DOR),
  o the number of patients that undergo a complete (microscopic radical R0) resection after treatment with brigatinib,
  o cumulative incidence of non-response or relapse on treatment and during follow-up,
  o event-free survival (EFS),
  o overall survival (OS),
  o on treatment survival.
• To describe histological response in resected specimens from IMT patients undergoing surgery after
  brigatinib treatment.
• To collect plasma concentration-time data for brigatinib to construct a population PK model, and to relate
  exposure to clinical response

In Cohort B2, ALK+ ALCL:

• To estimate the activity of brigatinib in terms of:
  o ORR after one course and best ORR during brigatinib treatment,
  o time to best response,
  o duration of response (DOR),
  o the cumulative incidence of non-response or relapse on treatment and after two years of brigatinib treatment,
  o overall survival (OS),
  o on treatment survival,
  o To describe outcome for ALCL patients with and without HSCT, after a remission induced with brigatinib.
  o To describe anti-tumor activity for ALCL patients that are re-challenged with brigatinib for a relapse occurring after brigatinib discontinuation.
• To assess the rate and time of MRD negativation for patients with positive MRD (both with and without measurable disease) at inclusion.
• To collect plasma concentration-time data for brigatinib and construct a population PK model, and to relate exposure to clinical response.

Pediatric and young adult patients with ALK-positive Anaplastic Large Cell Lymphoma (ALCL) , Inflammatory Myofibroblastic Tumors (IMT) or other solid tumors