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...

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.

Timeline

Start

2015-06-29

Primary completion

2027-10-30

Completion

2027-10-30

Publications

• Santiago-Sanchez G, Rosato F, Fabian KP, Padget MR, Lee JM, Karzai F, Schlom J, Gulley JL, Hamilton DH, Lee JK, Pruitt MR, Bayliffe A, Su Z, Moisan J, Katragadda M, Hodge JW. PARP inhibition combined with a T-cell receptor beta chain-directed antibody fusion molecule drives polyclonal antitumor immunity and tumor regression. J Immunother Cancer. 2026 Jul 1;14(7):e014518. doi: 10.1136/jitc-2025-014518.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications