DURVALUMAB for Advanced solid tumors | Haematological malignancies

Inclusion criteria

• {"criterion_text":"- 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.\n- If available, patients must provide a diagnostic tumor sample taken ˂3 years prior to screening for evaluation of PD-L1 status.\n- Lansky play performance scale ≥50 for patients ≥1 and <16 years of age and Karnofsky performance status score ≥50 for patients ≥16 years of age (patients <1 year of age are exempt from this criterion)\n- Patients must have measurable/evaluable disease as defined by methods used in common clinical practice.\n- No prior exposure to immune checkpoint inhibitors or genetically engineered cellular therapies including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies and CAR-T or other cell therapies, excluding therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after discussion with the Sponsor or designee."}

Exclusion criteria

• {"criterion_text":"- History of allogeneic organ transplantation. Patients who have previously received an autologous bone marrow transplant may be eligible\n- 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.\n- 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.\n- History of primary immunodeficiency.\n- 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).\n- 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. − Persistent toxicities (CTCAE Grade ≥2) caused by previous anticancer therapy, excluding alopecia. Patients with toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab in the opinion of the Investigator (eg, hearing loss, gastrostomy tube), may be included.\n- Patients with clinically active brain metastases (known or suspected), spinal cord compression, and choloromas are excluded, unless these conditions have been previously treated and are considered stable.\n- 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"}

Primary endpoints

• {"endpoint_text":"- Based on PK parameters (including Cmax, Cmin, AUC, and others), identify the adult equivalent exposure/MTD of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy, among children and young adults from birth to <18 years of age with advanced solid tumors using a q4w dosing schedule.","definition_or_measurement_approach":"PK parameters including Cmax, Cmin, AUC and others; q4w dosing schedule; identification of adult equivalent exposure/MTD via PK assessment."}
• {"endpoint_text":"- Identify the safety and tolerability of durvalumab in combination with tremelimumab and durvalumab as monotherapy following combination therapy, at the adult equivalent exposure/MTD among children and young adults from birth to <18 years of age with advanced solid tumor using a q4w dosing schedule. Endpoints include AEs, vital signs, physical examinations, ECGs, and laboratory evaluations","definition_or_measurement_approach":"Assessment of adverse events (AEs), vital signs, physical examinations, ECGs, and laboratory evaluations to determine safety and tolerability at adult equivalent exposure/MTD."}
• {"endpoint_text":"- Objective response rate as determined by the Investigator assessed RECIST 1.1 or alternative pre-specified tumor-specific response rates for different scoring systems. -Assessment of antitumor activity will be specific to tumor cohort, eg, Investigator assessed RECIST 1.1 (other malignancies will be analyzed based on the best response assessed by the Investigator).","definition_or_measurement_approach":"Objective response rate assessed by Investigator using RECIST 1.1 or alternative pre-specified tumor-specific response criteria; cohort-specific analysis."}
• {"endpoint_text":"- Additional efficacy endpoints that will be collected include DoR, BoR, DCR, PFS, APF12, and APF18 based on RECIST 1.1 assessed by the Investigator, and OS, OS12, and OS24 as appropriate","definition_or_measurement_approach":"Duration of Response (DoR), Best Overall Response (BoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), APF12, APF18 per RECIST 1.1 assessed by Investigator; Overall Survival (OS) and timepoint-specific OS (OS12, OS24) as appropriate."}

Secondary endpoints

• {"endpoint_text":"- Individual durvalumab and tremelimumab concentrations in serum, and PK parameters including Cmax, Cmin, AUC.","definition_or_measurement_approach":"Measurement of serum concentrations of durvalumab and tremelimumab and calculation of PK parameters including Cmax, Cmin, AUC."}
• {"endpoint_text":"- Number and percentage of patients who develop detectable ADAs.","definition_or_measurement_approach":"Assessment of anti-drug antibodies (ADAs); reporting number and percentage of patients with detectable ADAs."}
• {"endpoint_text":"- Individual antibody titer measurements before and after planned routine immunization during treatment and Cycle 4 or follow-up, whichever is earlier.","definition_or_measurement_approach":"Measurement of antibody titers pre- and post-routine immunizations during treatment and at Cycle 4 or at follow-up, whichever occurs earlier."}
• {"endpoint_text":"- Flow cytometry for CD4, CD8, B and NK cells, including T-cell activation with Ki67","definition_or_measurement_approach":"Flow cytometry assays measuring counts and activation (Ki67) of CD4, CD8, B, and NK cells."}

Spain

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

57

Number Of Sites

2

Number Of Participants

11

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

IQVIA Limited

Responsibilities

Sponsor duties codes present: 1, 12, 15 (Records Management), 5, 8; contact email: eu_clinical_trials_information@iqvia.com; phone: +441184506016

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Sponsor duties codes present: 1, 12, 15 (Records Management), 5, 8; contact email: eu_clinical_trials_information@iqvia.com","organisation_type":"Pharmaceutical company"}