Advanced Solid Tumors and Hematological Malignancies MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must have pathologically confirmed relapsed or refractory advanced solid tumour malignancy or haematological malignancies including lymphoma and acute leukaemia. Any number of prior treatment regimens allowed. A select group of first-line patients may be eligible for screening and enrolment. These patients will be enrolled based on investigator assessment as patients for whom no curative standard of care treatment options exist or such therapies are not tolerable. • If available, patients must provide a diagnostic tumor sample taken ?3 years prior to screening for evaluation of PD-L1 status. • Lansky play performance scale =50 for patients =1 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • History of allogeneic organ transplantation (exceptions may be allowed for HL, NHL, ALL and AML, after discussion with Sponsor or designee). Patients who have previously received an autologous bone marrow transplant may be eligible • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, celiac disease or other serious GI chronic conditions associated with diarrhea, systemic lupus erythematosus, Wegener syndrome; myasthenia gravis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc) autoimmune myocarditis, and autoimmune pneumonitis. The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement - Psoriasis that does not require systemic therapy - Patients with celiac disease controlled by diet alone. • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, ILD, or psychiatric illness or social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from IP, or compromise the ability of the patient to give written informed consent. • History of primary immunodeficiency. • Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV. Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). • Any unresolved toxicity NCI CTCAE version 5.0 Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia and the laboratory values defined in the inclusion criteria - Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician. - Patients with toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab (eg, hearing loss, gastrostomy tube) may be included after consultation with the Study Physician. • Patients with clinically active brain metastases (known or suspected) or spinal cord compression, and choloromas are excluded, unless these conditions have been previously treated and are considered stable. • History of leptomeningeal carcinomatosis, or involvement of any other anatomic area that, in the opinion of the Investigator, may cause significant symptoms if an inflammatory reaction occurs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose-finding: -To determine the adult equivalent exposure/MTD/recommended Phase II pediatric dose of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy. -To determine the safety profile of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy Dose-expansion: To determine the preliminary antitumor activity of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy at the recommended dose, using cohortspecific response criteria (eg, Cheson criteria and RECIST 1.1).;Secondary Objective: Dose-finding and dose-expansion: -To describe the PK of durvalumab and tremelimumab in combination and durvalumab as monotherapy following combination therapy, in children and young adults with solid tumors, or hematological malignancies -To determine the immunogenicity of durvalumab and tremelimumab in combination and durvalumab as monotherapy following combination therapy, in children and young adults with solid tumors -To determine the immunogenicity of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy, in children and young adults with hematological malignancies -To measure effects on immune checkpoint inhibition in response to routine immunizations (dose-expansion phase only). -To evaluate immune activation and counts of NK-, B- and T-cells;Primary end point(s): Dose-finding: 1. Based on PK parameters (including Cmax, Cmin, AUC, and others), identify the adult equivalent exposure/MTD of durvalumab monotherapy and durvalumab in combination with tremelimumab among children and young adults from birth to <18 years of age with advanced solid tumors and non-Hodgkin lymphoma, using a q4w dosing schedule. 2. Identify the safety and tolerability of durvalumab monotherapy and durvalumab in combination with tremelimumab at the adult equivalent exposure/MTD among child | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 5. Individual durvalumab and tremelimumab concentrations in serum, and PK parameters including Cmax, Cmin, AUC. 6. Number and percentage of patients who develop detectable ADAs. 7. Individual antibody titer measurements before and after planned routine immunization during treatment and Cycle 4 or follow-up, whichever is earlier. 8. Flow cytometry for CD4, CD8, B and NK cells, including T-cell activation with Ki67;Timepoint(s) of evaluation of this end point: 5. From first dose to cycle 12 on dosing days 6 & 7. Pre- first dose and pre-dose cycle 6 (durvalumab) and cycle 4 (tremelimumab) 8. From first dose to cycle 2 | — |
Countries
France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed