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 received and have progressed or are refractory to at least one line of standard systemic therapy in the recurrent/metastatic setting, appropriate for the specific tumor type. In addition, subjects must meet all of the tumor specific criteria specified in the protocol, with documented progression from previous therapy at study entry. Interval progression between two lines of therapy defines separate lines of therapy. Both standard and investigational treatments will count as lines of therapy when determining eligibility. 2. Subjects must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009). 3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 4. As of Week 1 Day 1, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic and meet the following: a. No concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids b. At least 28 days after CNS treatment, clinically stable with no symptoms of CNS metastasis or sequelae of radiation and at least 14 days since last dose of corticosteroids NOTE: Subjects with clinical symptoms or cord compression or with leptomeningeal disease are excluded from the study 5. Adequate organ function as determined by: a. Hematological (criteria i – iii cannot be met with recent blood transfusions or require ongoing growth factor support within 2 weeks of starting study treatment): i. Absolute neutrophil count = 1.5 × 109/L (1,500/mm3) ii. Platelet count = 100 × 109/L (100,000/mm3) iii. Hemoglobin = 9.0 g/dL within first 2 weeks prior to first dose b. Renal: Calculated creatinine clearance* (CrCl) or 24 hour urine CrCl > 50 mL/min c. Hepatic: i. TBL = 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin = 3 × ULN ii. AST and ALT = 2.5 × ULN (AST/ALT can be up to 5 × ULN in the presence of liver metastasis, but cannot be associated with elevated bilirubin) 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 190 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. Prior treatment with immunotherapy agents including, but not limited to tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or NK cell inhibitors including agents targeting KIR, PD-1, PDL1, CTLA-4, OX40, CD27, CD137 (4-1BB), CD357 (GITR), and CD40. 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 havenot yet been completed 3. Known allergic reaction to any component of durvalumab or IPH2201 4. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study 5. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of durvalumab and IPH2201 6. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for noncancer- related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. Local treatment (eg, by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the DLT evaluation period with prior consultation and in agreement with the medical monitor. 7. Receipt of live attenuated vaccines within 30 days prior to the first dose of investigational products. Subjects, if enrolled, should not receive live or live attenuated vaccine during the study and 30 days after the last dose of investigational products. 8. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the study drug may be included (eg, hearing loss) after consultation with the medical monitor 9. Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection), OR b. systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, OR c. steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication) 10. History of primary immunodeficiency or allogeneic transplantation 11. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease, Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded 12. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint is safety as assessed by presence of AEs, SAEs, DLTs, abnormal laboratory parameters, vital signs, and electrocardiogram (ECG) results. AEs will be graded according to the NCI CTCAE v4.03.; Main Objective: Primary objective: 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 IPH2201 in subjects with advanced solid tumors. ; Secondary Objective: Secondary objectives: 1. To determine the preliminary antitumor activity of durvalumab in combination with IPH2201 based on Response Evaluation criteria in Solid Tumors (RECIST) v1.1 2. To describe the pharmacokinetics (PK) of durvalumab in combination with IPH2201 and the PK of IPH2201 in combination with durvalumab 3. To describe the immunogenicity of durvalumab in combination with IPH2201 and the immunogenicity of IPH2201 in combination with durvalumab 4. To characterize the association between clinical outcomes to durvalumab in combination with IPH2201 and/or expression of PD-L1 and human leukocyte antigen (HLA-E) within the tumor microenvironment. ;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 based on RECIST v1.1 will include objective response (OR), disease control (DC), duration of response (DoR), progression-free survival (PFS), and OS. 2. The endpoints for assessment of PK of durvalumab and IPH2201 include individual subject concentrations in serum at different time points after administration of both agents. PK parameters that may be modeled on this data include, but are not limited to, peak concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and terminal elimination half-life (t1/2). 3. The endpoints for assessment of immunogenicity of durvalumab and IPH2201 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 tumor biopsies. ;Timepoint(s) of evaluation of this end point: Monitored throughout the study | — |
Countries
Canada, France, Hungary, Italy, Spain, United Kingdom, United States
Contacts
Public ContactAstraZeneca Study Info. Center
Medimmune LLC
Outcome results
None listed