NCT03107988

NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)

Phase 1 Study of Lorlatinib (PF-06463922), an Oral Small Molecule Inhibitor of ALK/ROS1, for Patients With ALK-Driven Relapsed or Refractory Neuroblastoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 65 (actual)
• Sponsor: New Approaches to Neuroblastoma Therapy Consortium · Academic / Other
• Sex: All
• Age: 1 Year – 99 Years
• Healthy volunteers: Not accepted

Summary

Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).

Detailed description

Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. An adult phase 1 study established an RP2D of 100mg QD for lorlatinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2). Lorlatinib will be administered orally via tablets or via oral dispersion if patient is unable to swallow tablets whole All patients will participate in mandatory pharmacokinetic testing.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	Lorlatinib	Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
DRUG	Cyclophosphamide	Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
DRUG	Topotecan	Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
DRUG	Filgrastim/pegfilgrastim	Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC \> 2000/mm\^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy. Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.

Timeline

• Start date: 2017-09-05
• Primary completion: 2024-08-22
• Completion: 2025-01-31
• First posted: 2017-04-11
• Last updated: 2025-09-15
• Results posted: 2025-09-15

Locations

13 sites across 4 countries: United States, Canada, France, United Kingdom

Regulatory

• FDA-regulated drug study