Testing the Combination of Two Immunotherapy Drugs (Magrolimab and Dinutuximab) in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma

Titre officiel

Phase 1 Trial of Hu5F9-G4 (Magrolimab) Combined With Dinutuximab in Children and Young Adults With Relapsed and Refractory Neuroblastoma or Relapsed Osteosarcoma

Sommaire:

Cet essai de phase I vise à déterminer la meilleure dose, les avantages et/ou les effets secondaires possibles du magrolimab en association avec le dinutuximab dans le traitement des patients atteints d’un neuroblastome qui est revenu (rechute) ou qui ne répond pas au traitement (réfractaire) ou d’un ostéosarcome récidivant. Le magrolimab et le dinutuximab sont des anticorps monoclonaux qui peuvent nuire à la capacité des cellules tumorales de se développer et de se propager. L’association du magrolimab et du dinutuximab peut faire régresser ou stabiliser un neuroblastome récidivant ou réfractaire ou un ostéosarcome récidivant. En outre, cet essai pourrait aider les chercheurs à déterminer s’il est sécuritaire d’administrer le magrolimab et le dinutuximab après une intervention chirurgicale visant à retirer des tumeurs des poumons.

Description de l'essai

Primary Outcome:

• Incidence of adverse events (dose finding cohort)
• Recommended phase 2 dose of magrolimab (dose finding cohort)
• Overall response rate (expansion cohort)
• Incidence of adverse events (expansion cohort)

Secondary Outcome:

• Pharmacokinetics (PK) of Hu5F9-G4 (magrolimab)
• Anti-tumour activity
• Event free survival

PRIMARY OBJECTIVES:

• Determine the safety and tolerability of Hu5F9-G4 (magrolimab) in combination with dinutuximab in children and young adults with relapsed/refractory (R/R) neuroblastoma (NBL) or relapsed osteosarcoma.
• Determine the recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) given in combination with dinutuximab in children and young adults.
• Determine the safety and feasibility of administering Hu5F9-G4 (magrolimab) in combination with dinutuximab to patients that undergo pulmonary resection of metastatic osteosarcoma within three weeks of surgery.

SECONDARY OBJECTIVES:

• Determine the pharmacokinetics (PK) of Hu5F9-G4 (magrolimab) in children and young adults.
• Evaluate the event free survival (EFS) in two cohorts of patients who are treated at the recommended phase 2 dose (RP2D) (measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection) and compare to historical controls.
• Observe and record anti-tumour activity.
• Evaluate the overall response rate (ORR) of patients in the NBL cohorts (measurable R/R NBL and evaluable R/R NBL) and osteosarcoma patients (measurable relapsed osteosarcoma) in the expansion cohorts treated at the RP2D.

EXPLORATORY OBJECTIVES:

• To explore biomarkers of response and resistance including genomic (CD47 expression, Fc receptor [FcR] polymorphisms, SIRPa polymorphisms, and KiR phenotype) and immunologic (dinutuximab HACA, magrolimab ADA, peripheral and bone marrow immune subsets, and circulating cytokines).
• To explore biomarkers of response in the tumour microenvironment through multiplexed ion beam imaging (MIBI) on resected tissue or archival tissues including comparison of pre- and post- treatment tumour tissues from patients undergoing staged resection of pulmonary osteosarcoma.

OUTLINE:
This is a dose de-escalation study of magrolimab with fixed-dose dinutuximab followed by a dose-expansion study. Patients are assigned to 1 of 2 arms.

ARM A: Patients receive magrolimab intravenously (IV) over 2 hours on days 1, 8, and 15 of cycles 1-2 and days 1 and 15 of subsequent cycles, and dinutuximab IV over 10 hours on days 2-5. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive magrolimab IV over 2 hours on days 1, 8, and 15 of cycles 1-2 and days 1 and 15 of subsequent cycles, and dinutuximab IV over 10 hours on days 2-5. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with pulmonary osteosarcoma may undergo surgical resection of tumour after cycle 1. After surgery, these patients continue receiving magrolimab and dinutuximab every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, at 2, 4, 6, 9, and 12 months, and then yearly for 4 years.

Voir cet essai sur ClinicalTrials.gov