Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Immune System Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Olaparib Oral Product

olaparib 300mg twice daily plus intravenous durvalumab every 28 days

Olaparib Oral Product in combination with Durvalumab

Sarah Sammons, MD

This is a randomized, international, multicenter, Phase II study designed to explore the efficacy of olaparib or olaparib in combination with durvalumab in platinum-treated mTNBC. The primary objectives are to explore olaparib or olaparib in combination with durvalumab as maintenance therapy following clinical benefit with platinum-based therapy in subjects with mTNBC.

Subjects suitable for enrollment into this trial are adult subjects with histologically documented triple negative adenocarcinoma of the breast that is inoperable, locally advanced, or metastatic, and is not amenable to resection with curative intent, and who have received at least 4 cycles of platinum-based chemotherapy in the 1st or 2nd line setting AND derived clinical benefit (CR / PR / SD) per RECIST 1.1 with platinum-based therapy as determined by the treating physician.

Eligible subjects will be randomized to either olaparib or olaparib in combination with durvalumab. Study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. Upon treatment discontinuation, subjects will be followed every 2 months for survival.

Although randomization will be used to allocate subjects to either the olaparib or olaparib in combination with durvalumab arm, no comparisons between treatment regimens are planned. The purpose of randomization was to reduce bias due to subject selection into either treatment arm.

Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer (DORA)

Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer

PFS, defined as the time from randomization to the first occurrence of disease progression or death from any cause on study for olaparib alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as events (disease progression or death) per month.

PFS, as defined as the time from randomization to the first occurrence of disease progression (as determined using RECIST v1.1 criteria and assessed by the investigator) or death from any cause on study for olaparib in combination with durvalumab. Death on study is defined as death from any cause within 30 days of the last dose of study treatment regimen. Reported as (disease progression or death) events per month.

To determine the efficacy of maintenance olaparib following platinum based chemotherapy as assessed by overall survival (OS).

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum based chemotherapy as assessed by overall survival (OS).

To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by overall response rate (ORR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

To determine the efficacy of maintenance olaparib following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for \>= 24 weeks.

To determine the efficacy of maintenance olaparib in combination with durvalumab following platinum-based chemotherapy as assessed by clinical benefit rate (CBR) based on RECIST 1.1 (Response Evaluation Criteria In Solid Tumors Criteria). Per RECIST v1.1 for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD); Clinical Benefit (CB) = CR + PR + SD for \>= 24 weeks.

AstraZeneca

Duke University

Assistant Professor of Medicine

Twice daily oral Olaparib 300mg alone as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Olaparib Oral Product: olaparib 300mg twice daily

A - Olaparib Alone

Twice daily oral olaparib plus intravenous Durvalumab every 4 weeks as maintenance therapy until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Olaparib Oral Product in combination with Durvalumab: olaparib 300mg twice daily plus intravenous durvalumab every 28 days

B - Olaparib Plus Durvalumab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Biostatistician

Assumed median PFS = 2.0 months as historical control, transformed to rate of 0.35/month

Intent To Treat population. Only applies to the "olaparib alone" arm.

Efficacy of Olaparib Alone as Assessed by PFS (Progression-free Survival) Reported as Events Per Month

Intent to Treat population. Only applies to the "olaparib plus durvalumab" arm.

Efficacy of Olaparib in Combination With Durvalumab as Assessed by PFS (Progression-free Survival)

Only applies to the "olaparib alone" arm.

Overall Survival (Olaparib Alone)

Only applies to the "olaparib plus durvalumab" arm.

Overall Survival (Olaparib in Combination With Durvalumab)

Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib Alone)

Overall Response Rate (ORR) as Measured by Number of Participants Achieving Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1 (Olaparib in Combination With Durvalumab)

Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib Alone)

Clinical Benefit Rate (CBR) as Measured by the Number of Participants Achieving Complete Response (CR), Partial Response (PR) or Stable Disease for ≥ 24 Weeks (SD) as Defined by RECIST 1.1. (Olaparib in Combination With Durvalumab)

Spots Global Cancer Trial Database for olaparib oral product in combination with durvalumab