Qarziba for Patients in Relapsed/Refractory High-grade Osteosarcoma

This is an interventional treatment trial for Osteosarcoma in Children Read More

Inclusion Criteria:

• Provision of signed and dated, written informed consent from each patient or patient's legally acceptable representative, parent (s) or legal guardian in accordance with regional laws or regulations and the patient's assent, when applicable, before any study-specific activity, including screening evaluation, is performed. For patients who reach the age of legal consent during the clinical study, notification may be required and a new consent form may need to be signed by the patient.
• Histologically confirmed high-grade osteosarcoma which is relapsed or refractory (ONLY patients in first or second relapse will be eligible). Histological confirmation from initial diagnosis or relapse is acceptable.
• Disease status: subjects must have achieved a complete or partial response after a second or further line of systemic therapy (with or without surgery) as defined by the following criteria:
• Complete Response = disappearance of all target and non-target lesions
• Partial Response = at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD of the last episode of relapse or recurrence. If a partial response is achieved, only patients with a focal localized disease at any site must be enrolled (for patients with lung disease a maximum of 2 lung unilateral nodules will be accepted).
• Age: ≥ 1 to < 25 years old at the time of signing the informed consent form.
• Performance Level: Karnofsky Performance Status ≥ 60% for participants > 16 years old or Lansky Play Score ≥ 60% for pediatric participants ≤ 16 years old. Subjects who are unable to walk because of paralysis and/or previous surgeries will be considered ambulatory for the purpose of assessing their performance score.
• Subjects must have recovered to < Grade 2 per the NCI CTCAE v 4.03 or to baseline from any non-hematologic toxicities (except alopecia) due to previous therapy.
• Life expectancy ≥ 3 months.
• Completed previous line of treatment (systemic therapy with or without surgery) within 28 days prior the first dose of Dinutuximab Beta.
• Adequate bone marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening
• Adequate organ function
• Normal ventricular ejection fraction (LV ejection fraction > 50%).
• Availability of paraffin tumor material and/or fresh frozen tumor sample of the most recent biopsy.

Exclusion Criteria:

• Any other malignancy that required treatment within 2 years prior to study drug administration;

• Concomitant Medications:

  • Anticancer agents: subjects who are currently receiving other anticancer agents
  • Corticosteroid: Due to their immunosuppressive activity, concomitant treatment with corticosteroids is not recommend within 2 weeks prior to the first treatment course until 1 week after the last treatment course with Dinutuximab Beta, except for life-threatening conditions

• Prior Therapies and/or Procedures:

  • Major surgery within 28 days prior to the first dose of Dinutuximab Beta.
  • Minor surgery within 14 days prior to the first dose of Dinutuximab Beta.
  • Received prior to treatment with Dinutuximab Beta or any other monoclonal antibody GD2.
  • Received prior to treatment with chimeric antigen receptor anti GD2 therapy (CAR-T anti GD2) within 28 days prior to the first dose of Dinutuximab Beta.
  • Received any anti-cancer drug within 28 days prior to the first dose of Dinutuximab Beta.
  • Received any investigational drug within 28 days prior to the first dose of Dinutuximab Beta.
  • Received radiotherapy or proton-therapy within 28 days prior to the first dose of Dinutuximab Beta.
  • Received any immunotherapy within 28 days prior to the first dose of Dinutuximab Beta.
  • Received any live (including attenuated) vaccines within 28 days prior the first dose of Dinutuximab Beta.
• Disease progression or presence of a multifocal disease after the induction therapy (except for the presence of only 2 unilateral lung diseases).
• Has hypersensitivity to either study drug or any of the excipients.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, auto-immune disease or psychiatric illness or social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from IP.
• Active infection including hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HbsAg]), hepatitis C, HIV (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HbsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
• Has peripheral or central neuropathy ≥ Grade 2 (CTCAE v 4.03).
• Has photophobia ≥ Grade 2 (CTCAE v 4.03).
• Has uncontrolled seizure disorder.
• Females who are pregnant or lactating.
• Willingness to avoid pregnancy or fathering children