Durvalumab and Tremelimumab for Pediatric Malignancies

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.

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

- Malignant neoplasms of hematopoietic and lymphoid tissue and myelodysplastic syndrome:
pathologically confirmed relapsed or refractory advanced hematological malignancies
including lymphoma and acute leukemia

- 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 HL, NHL,
ALL and AML, 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)