Trial Outcomes & Findings for Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents (NCT NCT04739800)

Last Updated: 2025-12-04

Results Overview

The relationship of randomized treatment assignment to progression free survival. The RECIST 1.1 criteria are used for disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

120 participants

Primary outcome timeframe

From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 4.8 months (Inter-Quartile Range: 2.0-7.9 months).

Results posted on

2025-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Overall Study STARTED	18	33	34	35
Overall Study COMPLETED	6	17	11	13
Overall Study NOT COMPLETED	12	16	23	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Overall Study Adverse Event	2	1	4	5
Overall Study Never Treated	2	0	1	1
Overall Study On Treatment	5	9	9	9
Overall Study Symptomatic Deterioration	1	1	3	0
Overall Study Withdrawal by Subject	1	2	1	3
Overall Study Other Reason	1	3	5	4

Baseline Characteristics

Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) n=18 Participants Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=33 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=34 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=35 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO	Total n=120 Participants Total of all reporting groups
Age, Customized 20 - 29	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	0 Participants n=15 Participants
Age, Customized 30 - 39	0 Participants n=3 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants	1 Participants n=3 Participants	2 Participants n=15 Participants
Age, Customized 40 - 49	0 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants	3 Participants n=3 Participants	5 Participants n=15 Participants
Age, Customized 50 - 59	5 Participants n=3 Participants	12 Participants n=3 Participants	7 Participants n=6 Participants	7 Participants n=3 Participants	31 Participants n=15 Participants
Age, Customized 60 - 69	9 Participants n=3 Participants	17 Participants n=3 Participants	13 Participants n=6 Participants	18 Participants n=3 Participants	57 Participants n=15 Participants
Age, Customized 70 - 79	4 Participants n=3 Participants	3 Participants n=3 Participants	10 Participants n=6 Participants	6 Participants n=3 Participants	23 Participants n=15 Participants
Age, Customized >= 80	0 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=6 Participants	0 Participants n=3 Participants	2 Participants n=15 Participants
Sex: Female, Male Female	18 Participants n=3 Participants	33 Participants n=3 Participants	34 Participants n=6 Participants	35 Participants n=3 Participants	120 Participants n=15 Participants
Sex: Female, Male Male	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	0 Participants n=15 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=3 Participants	3 Participants n=3 Participants	1 Participants n=6 Participants	1 Participants n=3 Participants	5 Participants n=15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=3 Participants	29 Participants n=3 Participants	33 Participants n=6 Participants	33 Participants n=3 Participants	113 Participants n=15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	1 Participants n=3 Participants	0 Participants n=6 Participants	1 Participants n=3 Participants	2 Participants n=15 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=3 Participants	1 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	1 Participants n=15 Participants
Race (NIH/OMB) Asian	1 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants	0 Participants n=3 Participants	3 Participants n=15 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Black or African American	0 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=6 Participants	2 Participants n=3 Participants	4 Participants n=15 Participants
Race (NIH/OMB) White	16 Participants n=3 Participants	28 Participants n=3 Participants	30 Participants n=6 Participants	32 Participants n=3 Participants	106 Participants n=15 Participants
Race (NIH/OMB) More than one race	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=3 Participants	0 Participants n=15 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=3 Participants	3 Participants n=3 Participants	1 Participants n=6 Participants	1 Participants n=3 Participants	6 Participants n=15 Participants
Prior Parp Inhibitor Treatment (Stratification Factor) Yes	9 Participants n=3 Participants	16 Participants n=3 Participants	16 Participants n=6 Participants	18 Participants n=3 Participants	59 Participants n=15 Participants
Prior Parp Inhibitor Treatment (Stratification Factor) No	9 Participants n=3 Participants	17 Participants n=3 Participants	18 Participants n=6 Participants	17 Participants n=3 Participants	61 Participants n=15 Participants
Prior Immune Therapy Treatment (Stratification Factor) Yes	3 Participants n=3 Participants	3 Participants n=3 Participants	2 Participants n=6 Participants	5 Participants n=3 Participants	13 Participants n=15 Participants
Prior Immune Therapy Treatment (Stratification Factor) No	15 Participants n=3 Participants	30 Participants n=3 Participants	32 Participants n=6 Participants	30 Participants n=3 Participants	107 Participants n=15 Participants

PRIMARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 4.8 months (Inter-Quartile Range: 2.0-7.9 months).

Population: All Randomized Subjects

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) n=18 Participants Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=33 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=34 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=35 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Progression Free Survival	4.2 Months Interval 1.9 to 5.0	2.6 Months Interval 2.0 to 4.2	2.3 Months Interval 2.0 to 4.6	2.3 Months Interval 2.1 to 3.9

SECONDARY outcome

Timeframe: From the start of the treatment until disease progression/recurrence, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Population: Patients with measurable disease, a baseline tumor assessment, and at least one on-treatment tumor assessment. The study was terminated for futility of all the experimental arms. Many patients withdrew from treatment prior to their first on-treatment tumor assessment.

Determination of response should take into consideration all target and non-target lesions. Here are the definitions of CR, PR, PD and SD: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters (i.e. the nadir) while on study. The CI is the Jeffreys interval.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) n=10 Participants Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=21 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=20 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=18 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Objective Response Rate	0 Proportion of Participants Interval 0.0 to 0.217	0.048 Proportion of Participants Interval 0.005 to 0.202	0.150 Proportion of Participants Interval 0.044 to 0.349	0.111 Proportion of Participants Interval 0.024 to 0.311

SECONDARY outcome

Timeframe: Throughout study treatment, up to 10.6 months.

Population: Patients with Complete or Partial Response

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. Duration of response was defined as the time from the first documentation of objective tumor response (complete response (CR) or partial response (PR)) to the first documented progressive disease (PD), or to death due to any cause, whichever occurs first. Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) is defined 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. Reporting the number of months from complete or partial response until disease progression, death or censoring, whichever occurs first. In the absence of disease progression or death, censoring time is based on date of last CT scan.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=1 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=3 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=2 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Duration of Response	—	2.3 days (censored, progressive disease) Interval 2.3 to 2.3	4.1 days (censored, progressive disease) Interval 2.1 to 5.8	6.5 days (censored, progressive disease) Interval 3.4 to 9.7

SECONDARY outcome

Timeframe: Time from study entry to date of death from any cause, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Population: All randomized subjects

Overall survival will be presented by Kaplan Meier methods. Overall Survival (OS) is defined as the duration of time from study entry to date of death from any cause. A subject who has not died will be censored on the date that they were last known to be alive.

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) n=18 Participants Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=33 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=34 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=35 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Overall Survival	6.4 months Interval 4.8 to Insufficient number of events to estimate parameter.	4.9 months Interval 3.4 to Insufficient number of events to estimate parameter.	5.7 months Interval 3.1 to Insufficient number of events to estimate parameter.	9.4 months Interval 3.4 to Insufficient number of events to estimate parameter.

SECONDARY outcome

Timeframe: From the start of treatment until disease progression/recurrence or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Population: Safety Population

The number of patients (in each reporting group) who experienced a grade 3 (or higher) adverse event

Outcome measures

Outcome measures
Measure	Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride)) n=14 Participants Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Paclitaxel: Given IV Pegylated Liposomal Doxorubicin Hydrochloride: Given IV Topotecan Hydrochloride: Given IV	Arm II (Durvalumab, Cediranib Maleate, Olaparib) n=29 Participants Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA Olaparib: Given PO	Arm III (Durvalumab, Cediranib Maleate) n=26 Participants Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Durvalumab: Given IV Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Multigated Acquisition Scan: Undergo MUGA	Arm IV (Cediranib Maleate, Olaparib) n=29 Participants Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial. Biospecimen Collection: Undergo collection of blood Cediranib Maleate: Given PO Computed Tomography: Undergo CT Computed Tomography with Contrast: Undergo CT with contrast Echocardiography: Undergo ECHO Magnetic Resonance Imaging: Undergo MRI Olaparib: Given PO
Count of Participants With a Grade 3 (or Higher) Adverse Event	7 Participants	19 Participants	14 Participants	18 Participants

Adverse Events

Arm I (Paclitaxel, Doxorubicin, Topotecan Hydrochloride))

Serious events: 8 serious events

Other events: 12 other events

Deaths: 4 deaths

Arm II (Durvalumab, Cediranib Maleate, Olaparib)

Serious events: 19 serious events

Other events: 25 other events

Deaths: 12 deaths

Arm III (Durvalumab, Cediranib Maleate)

Serious events: 14 serious events

Other events: 24 other events

Deaths: 13 deaths

Arm IV (Cediranib Maleate, Olaparib)

Serious events: 18 serious events

Other events: 28 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Christopher Purdy on behalf of Austin Miller, PhD

NRG Oncology

Phone: (716) 845-1300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60