Advanced solid tumor
Conditions
Sponsors
MedImmune, LLC, a wholly owned subsidiary of AstraZeneca PLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have histologic documentation of advanced recurrent or metastatic cancer. 2. Subjects must be at the recurrent/metastatic setting, with selected advanced solid tumors. 3. Subjects must have at least one lesion that is measurable by RECIST v1.1 4. Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have received more than two lines of systemic therapy in the recurrent/metastatic setting. Please refer to the protocol for a full list of the inclusion criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 596 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor. 2. Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed 3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment 4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable Please refer to the protocol for a full list of the exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To assess safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or the highest protocol-defined dose level in the absence of establishing an MTD of durvalumab in combination with monalizumab in subjects with selected advanced solid tumors. Part 2: To assess further the safety and tolerability of either the MTD or the highest protocol-defined dose level, in the absence of establishing an MTD, of durvalumab in combination with monalizumab in subjects with selected advanced solid tumors. Part 3: To assess safety and tolerability of durvalumab in combination with monalizumab plus chemotherapy with or without a biologic agent, as clinically indicated in subjects with MSS-CRC. Please refer to the protocol for a full list of the Primary objectives.;Secondary Objective: For the combinations under investigation in this trial: • To evaluate preliminary anti-tumor activity • To further evaluate the anti-tumor activity • To describe the pharmacokinetics (PK) of each agent in the combinations under investigation • To describe the immunogenicity • To characterise the association between clinical and/or pre-treatment expression of PD-L1 and human leukocyte antigen (HLA-E) within the tumor microenvironment Please refer to the protocol for a full list of the secondary objectives.;Primary end point(s): The primary endpoint is safety as assessed by presence of adverse events (AEs), serious adverse events (SAEs), DLTs, abnormal laboratory parameters, vital signs, and electrocardiogram (ECG) results. AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. The primary endpoint for evaluating clinical activity in Part 3 (Cohorts C1A and C1B) is objective response (OR) by investigator assessment per RECIST v1.1.;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 The endpoints for assessment of antitumor activity will include objective response (OR [primary endpoint for Cohorts C1A and C1B]), disease control (DC), duration of response (DoR), and progression-free survival (PFS) by investigator assessment per RECIST v1.1. Overall survival (OS) will also be assessed. 2 The endpoints for assessment of PK include individual subjects' investigational product concentrations in serum at different time points after administration of these agents. 3 The endpoints for assessment of immunogenicity include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs). 4 The endpoints for assessment of biomarkers predicting subject clinical outcomes will include expression of PD-L1 and HLA-E in pre-treatment tumor biopsies.;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Countries
Australia, Belgium, Brazil, Canada, France, Hungary, Italy, Korea, Republic of, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactAstraZeneca Study Info. Center
Medimmune LLC
Outcome results
None listed