Durvalumab and Tremelimumab for Pediatric Malignancies

AstraZeneca

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Solid Tumor Pediatric; Hematological Malignancies; Pediatric Cancer

Treatments: Drug: Durvalumab / Tremelimumab Combination Therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT03837899

2018-003118-42 (EudraCT Number)

D419EC00001

Details and patient eligibility

About

The purpose of the study is to determine the recommended dose of durvalumab and tremelimumab (immunotherapy drugs) in pediatric patients with advanced solid and hematological cancers and expand in a second phase to test the efficacy of these drugs once this dose is determined.

Full description

This is a first time in pediatrics study primarily designed to evaluate the safety and tolerability of durvalumab and durvalumab in combination with tremelimumab at increasing doses in pediatric patients with advanced solid malignancies and hematological malignancies (including lymphomas) and for whom no standard of care treatments exist. Although treatment efficacy is not a primary objective of this study given its early phase nature, the patients screened for this study have no curative options and this study offers the potential of some benefit.

The study will also characterize the PK of durvalumab and durvalumab in combination with tremelimumab in children and adolescents and explore potential biological activity and immunogenicity by assessing pharmacodynamics, anti drug antibody (ADA) levels, and anti-tumor activity. The results from this trial will form the basis for decisions for potential future pediatric studies

Enrollment: 50 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Max Age =17 years
• Solid Tumors (except primary central nervous system malignant tumors): Patients must have a histopathologic confirmation of malignancy. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist
• Non-Hodgkin's Lymphoma, limited to primary mediastinal B-cell lymphoma and anaplastic large cell lymphoma. Patients must have progressed or are refractory to standard therapies, and for whom no standard of care treatments exist.
• Provision of diagnostic tumor sample mandated if available
• Evaluable disease
• No prior exposure to immune-mediated therapy
• Adequate organ and marrow function
• Life expectancy of at least 3 months

Exclusion criteria

• History of allogeneic organ transplantation (exceptions may be allowed for NHL after discussion with Sponsor). History of autologous bone marrow transplant may be allowed (after discussion with Sponsor).
• Active or prior documented autoimmune or inflammatory disorders (exceptions)
• Uncontrolled intercurrent illness
• History of primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, C or HIV
• Any unresolved toxicity NCI CTCAE version 5.0 Grade ≥2 from previous anticancer therapy (exceptions)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Durvalumab / Tremelimumab Combination Therapy

Experimental group

Description:

Part 1 (dose finding) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are initially administered at dose level 1 and dose escalated based on results from PK modeling and tolerance to determine the RP2D. Both drugs are administered every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvavalumab for 4 doses, from cycles 2-5. (sarcoma, NB and NHL) Part 2 (dose expansion phase) Durvalumab + tremelimumab Combination Treatment. Durvalumab and tremelimumab are administered at the RP2D, every 4 weeks as intravenous infusions. Tremelimumab is only administered with durvalumab for 4 doses, from cycles 1-4. Tremelimumab may be added for 4 doses at time of progressive disease. Cohorts: solid tumors, sarcomas, NHL restricted to PMBCL and ALCL subtypes)

Treatment:

Drug: Durvalumab / Tremelimumab Combination Therapy