Background: - MEDI4736 is a drug that may help people s immune systems respond to and kill cancer cells. Olaparib is a drug that may inhibit repairing DNA damage of cancer cells. Cediranib is a drug that may stop the blood vessel growth of cancer cells. This study has two components. In the phase 1 component of the study, researchers want to investigate how well participants tolerate the combination of these drugs in treating advanced solid tumors, and in the phase 2 part of this study, researchers want to study if the combination treatments are effective in ovarian cancer. Objectives: - Phase 2 part of the study: To determine how effective this combination is in treating ovarian cancer. Eligibility: - Phase 2 part of the study: Adults age 18 or older with advanced or recurrent ovarian cancer that has no standard treatment. Design: - Participants will be screened with medical history, physical exam, and blood and urine tests. They will have CT or MRI scans. For these, they will lie in a machine that takes pictures of their bodies. - Phase 2 part of the study requests the participants to have tumor samples removed. - Participants will get MEDI4636 through an IV. A small plastic tube will be inserted into a vein. The drug will be given every 4 weeks until disease progression. - Participants will take olaparib or cediranib by mouth every day. - Every 28 days will be 1 cycle. For cycle 1, participants will have 2 study visits. All other cycles, they will have 1 visit. At these visits, they will repeat the screening procedures. - Patients will keep a drug and diarrhea diary. - Patients on cediranib will monitor their blood pressure and keep a blood pressure diary. - Participants who can become pregnant, or have a partner who can become pregnant, must practice an effective form of birth control. - After 12 cycles, participants will have 1-3 months of follow-up.
Name: Olaparib
Name: Cediranib
Name: MEDI4736
Description: Determination of the recommended phase II dose (RP2D) Safety: number of Adverse events
Measure: Ph I Determine the recommended phase II dose (RP2D) and the safety of doublet therapies of MEDI4736/olaparib (MEDI-O) and MEDI4736/cediranib (MEDI-C) in patients with advanced solid tumors Time: 28 DaysDescription: Overall response rate
Measure: Ph II Determine overall response rate of MED-O and MEDI-C in patients with recurrent ovarian cancer Time: Every 4 wks for Toxicity and every 8 wks for responseDescription: Safety: number of Adverse events
Measure: Ph I doublet tx: determin the safety of the doublets, MEDI+O and MEDI+C Time: every 28 daysDescription: Response : Preliminary response rate
Measure: Ph I doublet tx:determine preliminary response rates of the doublets using RECIST v1.1 Time: every 8 weeksDescription: Pharmacokinetics + Safety: adverse events
Measure: Ph I doublet tx: determine the pharmacokinetics of the doublets and correlate with safety. Time: Cycle 1 Days 1 and 15; Cycles 2 and beyond Day 1Description: Correlative laboratory research results + safety (adverse events) and/or clinical outcome
Measure: Ph I doublet tx: explore changes in peripheral immune subsets, plasma cytokines and circulating endothelial cells with safety and/or clinical outcome of MEDI+C Time: every 28 daysDescription: PD-L1 expression obtained from archival tissue samples and clinical response
Measure: Ph I doublet:determine the potential relationship between PD-L1 expression obtained from archival tissue samples and clinical response Time: every 28 daysDescription: Safety (adverse events)
Measure: Ph I of triplet tx: determine the safety of MEDI+O+C Time: every 28 daysDescription: Response: Preliminary response rate
Measure: Ph I of triplet tx: determine preliminary response rates of MEDI+O+C using RECIST v1.1 Time: every 8 weeksDescription: Pharmacokinetics + Safety: adverse events
Measure: Ph I of triplet tx:determine the pharmacokinetics of the triplet and correlate with safety. Time: Cycle 1 Days 1 and 15; Cycles 2 and beyond Day 1Description: Correlative laboratory research results + safety (adverse events) and/or clinical outcome
Measure: Ph I of triplet tx: explore changes in peripheral immune subsets, plasma cytokines and circulating endothelial cells with safety and/or clinical outcome of MEDI+O+C Time: every 28 daysDescription: PD-L1 expression obtained from archival tissue samples and clinical response
Measure: Ph I of triplet tx: determine the potential relationship between PD-L1 expression obtained from archival tissue samples and clinical response Time: every 28 daysDescription: Progression-Free Survival (PFS) + safety (adverse events) + PD-L1 expression ontained from biopsies and clinical response
Measure: Ph II Cohort 1 OvCa; MEDI+O, MEDI+C and MEDI+O+C arms: To evaluate PFS, safety by CTCAE v4.0, and potential relationship between pretreatment tumor PD-L1 expression obtained from biopsies and clinical response Time: every 28 days, every 8 weeksDescription: ORR + Safety (adverse events)
Measure: Ph II Cohort 2 NSCLC; MEDI+O and MEDI+C arms: To determine ORR, and safety by CTCAE v4.0 Time: every 28 days, every 8 weeksDescription: PFS + Safety (adverse events)
Measure: Ph II Cohort 3 SCLC; MEDI+O arm: To determine PFS and safety by CTCAE v4.0 Time: every 28 days, every 8 weeksDescription: ORR + safety (adverse events), duration of response and PSA responses.
Measure: Ph II Cohort 4 mCRPC; MEDI+O arm: To determine ORR, safety by CTCAE v4.0, duration of response and PSA responses. Time: every 28 days, every 8 weeksDescription: ORR + safety (adverse events)
Measure: Ph II Cohort 5 TNBC; MEDI+O arm: To determine PFS, safety by CTCAE v4.0, and potential relationship between pretreatment tumor PD-L1 expression obtained from biopsies and clinical response Time: every 28 days, every 8 weeksAllocation: Non-Randomized
Sequential Assignment
There is one SNP
PHASE II MEDI4736 PLUS OLAPARIB OR CEDIRANIB STUDY ELIGIBILITY CRITERIA - NON-SMALL CELL LUNG CANCER - Histologically or cytologically confirmed advanced NSCLC with at least one prior line of platinum-based chemotherapy (or treatment with EGFR, ALK, or BRAF-targeted tyrosine kinase inhibitors if tumors harbor an EGFR-sensitizing mutation, ALK translocation, or BRAF V600E mutation, respectively). --- V600E ---