Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...

NCT02484404 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 15014515-C-0145
• Study Type: interventional
• Target: 268
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Durvalumab 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 Durvalumab 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.

Conditions

Colorectal Neoplasms; Breast Neoplasms

Keywords

Immune Checkpoint Inhibitor; PARP Inhibitor; VEGFR Inhibitor

Outcome Measures

Primary Outcomes (2)

• Ph II Determine overall response rate of Durvalumab-O and Durvalumab-C in patients with recurrent ovarian cancer

  Overall response rate

  every 4 wks for toxicity and every 8 wks for response

• Ph I Determine the recommended phase II dose (RP2D) and the safety of doublet therapies of Durvalumab/olaparib (Durvalumab-O) and Durvalumab/cediranib (Durvalumab-C) in patients with advanced solid tumors

  Determination of the recommended phase II dose (RP2D) Safety: number of Adverse events

  28 days

Secondary Outcomes (15)

• Ph II Cohort 5 TNBC; Durvalumab+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

  every 28 days, every 8 weeks

• Ph II Cohort 4 mCRPC; Durvalumab+O arm: To determine ORR, safety by CTCAE v4.0, duration of response and PSA responses.

  every 28 days, every 8 weeks

• Ph II Cohort 3 SCLC; Durvalumab+O arm: To determine PFS and safety by CTCAE v4.0

  every 28 days, every 8 weeks

• Ph II Cohort 2 NSCLC; Durvalumab+O and Durvalumab+C arms: To determine ORR, and safety by CTCAE v4.0

  every 28 days, every 8 weeks

• Ph II Cohort 1 OvCa; Durvalumab+O, Durvalumab+C and Durvalumab+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

  every 28 days, every 8 weeks

Study Arms (6)

P1 Durvalumab+C

EXPERIMENTAL

Ph I Durvalumab + cediranib dose escalation

Drug: Cediranib; Drug: Durvalumab

P1 Durvalumab+O

EXPERIMENTAL

Ph I Durvalumab + olaparib dose escalation

Drug: Olaparib; Drug: Durvalumab

P1 Durvalumab+O+C

EXPERIMENTAL

Ph I Durvalumab + olaparib + cediranib dose escalation

Drug: Olaparib; Drug: Cediranib; Drug: Durvalumab

P2 Durvalumab+C

EXPERIMENTAL

Ph II Durvalumab + cediranib at RP2D

Drug: Cediranib; Drug: Durvalumab

P2 Durvalumab+O

EXPERIMENTAL

Ph II Durvalumab + olaparib at RP2D

Drug: Olaparib; Drug: Durvalumab

P2 Durvalumab+O+C

EXPERIMENTAL

Ph II Durvalumab + olaparib + cediranib at RP2D

Drug: Olaparib; Drug: Cediranib; Drug: Durvalumab

Interventions

Olaparib DRUG

Olaparib tablets will be given orally on a continuous dosing schedule. The DLT period will be one cycle, 28 days. MEDI4736 (3mg/kg or 10mg/kg IV) and Olaparib tablets (200 mg or 300 mg BID) Ph II - MEDI4736 + Olaparib at RP2D

P1 Durvalumab+O; P1 Durvalumab+O+C; P2 Durvalumab+O; P2 Durvalumab+O+C

Cediranib DRUG

Cediranib will be given orally on a continuous dosing schedule. The DLT period will be one cycle, 28 days. MEDI4736 (10mg/kg IV) and Cediranib (15 mg or 20 mg or 30 mg daily) Ph II - MEDI4736 + Cediranib at RP2D

P1 Durvalumab+C; P1 Durvalumab+O+C; P2 Durvalumab+C; P2 Durvalumab+O+C

Durvalumab DRUG

Ph I - Durvalumab will be administered once every 2 weeks for 12 months.

P1 Durvalumab+C; P1 Durvalumab+O; P1 Durvalumab+O+C; P2 Durvalumab+C; P2 Durvalumab+O; P2 Durvalumab+O+C

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 18 years of age.
• Patients must have adequately controlled blood pressure on a maximum of three antihypertensive medications.
• Patients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities.
• Patients with any cardiac history of the following conditions within 1 year prior to study enrollment are excluded from the study:
• Prior events including myocardial infarction, pericardial effusion, and myocarditis.
• Prior cardiac arrhythmia including atrial fibrillation and atrial flutter, or requiring concurrent use of drugs or biologics with pro-arrhythmic potential.
• NYHA Class II or greater heart failure.
• If cardiac function assessment is clinically indicated or performed, an LVEF less than normal per institutional guidelines, or \<55%, if threshold for normal is not otherwise specified by institutional guidelines.
• QTc prolongation \>470 msec or other significant ECG abnormality noted within 14 days of treatment.
• Hypertensive crisis or hypertensive encephalopathy.
• Clinically significant peripheral vascular disease or vascular disease, including rapidly growing aortic aneurysm or abdominal aortic aneurysm \>5 cm or aortic dissection.
• Unstable angina.
• Eligibility for patients with asymptomatic and a previous diagnosis of immune or inflammatory colitis, or patients with chronic diarrhea \> 1 month without immune or inflammatory colitis is a PI decision on an individual patient basis.
• Patients with a history of cerebrovascular accident or transient ischemic attack within 1 year prior to study enrollment are not eligible.
• Patients with a history of previous clinical diagnosis of tuberculosis are not eligible.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Li C, Madan RA, Lee MJ, Lee S, Sato N, Rastogi S, Shrestha R, Aragon-Ching JB, Goswami M, Donahue RN, Cordes LM, Baj A, Seo CCY, Terrigino NT, Bright JR, Hennigan ST, King IM, Trostel SY, Fenimore JM, Liu Y, Calzone KA, Schlom J, Gulley JL, Dahut WL, Figg WD, Sowalsky AG, Lee JM, Karzai F. Phase II study of olaparib and durvalumab in patients with metastatic castration-resistant prostate cancer. J Immunother Cancer. 2026 Mar 25;14(3):e014365. doi: 10.1136/jitc-2025-014365.

  PMID: 41881502 DERIVED

• Fujii T, Cimino-Mathews A, Lipkowitz S, Lee MJ, Nair J, Solarz BB, Zimmer A, Redd B, Levy EB, Rastogi S, Sato N, McCoy A, Steinberg SM, Lee JM. A Phase II Pilot Study of Anti-PD-L1, Durvalumab, and a PARP Inhibitor, Olaparib in Patients With Metastatic Triple-Negative Breast Cancer With or Without Germline BRCA Mutation. Cancer Med. 2025 Dec;14(23):e71220. doi: 10.1002/cam4.71220.

  PMID: 41360639 DERIVED

• Zimmer AS, Nichols E, Cimino-Mathews A, Peer C, Cao L, Lee MJ, Kohn EC, Annunziata CM, Lipkowitz S, Trepel JB, Sharma R, Mikkilineni L, Gatti-Mays M, Figg WD, Houston ND, Lee JM. A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. J Immunother Cancer. 2019 Jul 25;7(1):197. doi: 10.1186/s40425-019-0680-3.

  PMID: 31345267 DERIVED

• Karzai F, VanderWeele D, Madan RA, Owens H, Cordes LM, Hankin A, Couvillon A, Nichols E, Bilusic M, Beshiri ML, Kelly K, Krishnasamy V, Lee S, Lee MJ, Yuno A, Trepel JB, Merino MJ, Dittamore R, Marte J, Donahue RN, Schlom J, Killian KJ, Meltzer PS, Steinberg SM, Gulley JL, Lee JM, Dahut WL. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer. 2018 Dec 4;6(1):141. doi: 10.1186/s40425-018-0463-2.

  PMID: 30514390 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms; Breast Neoplasms

Interventions

olaparib; cediranib; durvalumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Takeo Fujii, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 29, 2015
• Study Start: June 29, 2015
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)