Trial Outcomes & Findings for Olaparib in Combination With Either Durvalumab, Selumetinib, or Capivasertib or Ceralasertib Alone in Treating Patients With Metastatic Triple Negative Breast Cancer (NCT NCT03801369)

Last Updated: 2025-11-21

Results Overview

Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

End of treatment (Up to 24 months)

Results posted on

2025-11-21

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (olaparib, durvalumab) Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Overall Study STARTED	24	0	0	0
Overall Study COMPLETED	24	0	0	0
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Olaparib in Combination With Either Durvalumab, Selumetinib, or Capivasertib or Ceralasertib Alone in Treating Patients With Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Olaparib, Durvalumab) n=24 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (Olaparib, Selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (Olaparib, Capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (Ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=68 Participants	—	—	—	20 Participants n=225 Participants
Age, Categorical >=65 years	4 Participants n=68 Participants	—	—	—	4 Participants n=225 Participants
Age, Continuous	54 Years n=68 Participants	—	—	—	54 Years n=225 Participants
Sex: Female, Male Female	24 Participants n=68 Participants	—	—	—	24 Participants n=225 Participants
Sex: Female, Male Male	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=68 Participants	—	—	—	24 Participants n=225 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Race (NIH/OMB) Asian	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Race (NIH/OMB) Black or African American	1 Participants n=68 Participants	—	—	—	1 Participants n=225 Participants
Race (NIH/OMB) White	21 Participants n=68 Participants	—	—	—	21 Participants n=225 Participants
Race (NIH/OMB) More than one race	0 Participants n=68 Participants	—	—	—	0 Participants n=225 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=68 Participants	—	—	—	2 Participants n=225 Participants
Region of Enrollment United States	24 participants n=68 Participants	—	—	—	24 participants n=225 Participants

PRIMARY outcome

Timeframe: End of treatment (Up to 24 months)

Population: No participants were enrolled in Arm II - Arm IV.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=21 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Objective Response Rate (ORR)	6 Participants	—	—	—

SECONDARY outcome

Timeframe: End of treatment (Up to 24 months)

Population: No participants were enrolled in Arm II - Arm IV.

An estimate of CBR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a CR, PR, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=21 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Clinical Benefit Rate (CBR)	10 Participants	—	—	—

SECONDARY outcome

Timeframe: End of treatment (Up to 24 months)

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Progression or death (any cause) up to 1 year post treatment

Population: No participants were enrolled in Arm II - Arm IV.

PFS is defined as the time after having completed at least one cycle of olaparib monotherapy to the first of either recurrence or relapse (anywhere in the body) or death at the time of last follow-up at 12-months. The estimated distribution of the PFS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=20 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Progression-free Survival (PFS)	4.8 months Interval 2.17 to 8.97	—	—	—

SECONDARY outcome

Timeframe: Death (any cause) up to 1 year post treatment

Population: No participants were enrolled in Arm II - Arm IV.

OS is defined as the time after having completed at least one cycle of olaparib monotherapy up to 6 months following the completion of on-study treatment to the date of death or last follow-up at 12 months. The estimated distribution of the OS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=24 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Overall Survival (OS)	15.5 months Interval 7.85 to 18.1	—	—	—

SECONDARY outcome

Timeframe: Up to 3 months post treatment

Population: No participants were enrolled in Arm II - Arm IV.

Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=24 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Incidence of Grade 3+ Acute Toxicity	46 occurrences	—	—	—

SECONDARY outcome

Timeframe: Up to 3 months post treatment

Population: No participants were enrolled in Arm II - Arm IV.

Outcome measures

Outcome measures
Measure	Arm I (olaparib, durvalumab) n=24 Participants Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Incidence of Grade 3+ Acute Toxicity	16 participants	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to end of treatment (Up to 24 months)

The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQC30 is a 30-item measure and yields scores for 5 functional scales (physical, role, cognitive, social, and emotional), 3-symptom scales (nausea, pain, and fatigue), a global health and QOL scale, and perceived financial impact of treatment. QLQC30 can distinguish patients according to performance status and is the most commonly used QOL instrument in oncology research. Data from the EORTC QLQ-C30 instrument will be scored as previously described by Aaronson et al.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to end of treatment (Up to 24 months)

The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQBR23 is a 23-item instrument that measures symptoms and side effects related to treatment, body image, sexuality, and future perspective specific to breast cancer patients. QLQBR23 has high internal consistency (Cronbach's a = 0.71-0.90), can distinguish between patients based on disease stage, performance status, treatment modality, or prior surgery, and is sensitive to change over time. The EORTC QLQ-BR23 data will be scored as described by the EORTC scoring manual.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (olaparib, durvalumab)

Serious events: 2 serious events

Other events: 24 other events

Deaths: 19 deaths

Arm II (olaparib, selumetinib)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm III (olaparib, capivasertib)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm IV (ceralasertib)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (olaparib, durvalumab) n=24 participants at risk Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Social circumstances Motor Vehicle Accident	4.2% 1/24 • Number of events 1 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.2% 1/24 • Number of events 1 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.

Other adverse events

Additional Information

Gordon Mills, MD, PhD

Oregon Health & Science University - Knight Cancer Institute

Phone: 503-346-4660

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I (olaparib, durvalumab) n=24 participants at risk Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Durvalumab: Given IV (infusion) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm II (olaparib, selumetinib) Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies Selumetinib: Given PO (orally)	Arm III (olaparib, capivasertib) Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Capivasertib: Given PO (orally) Olaparib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies	Arm IV (ceralasertib) Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles. Biopsy: Undergo biopsy Ceralasertib: Given PO (orally) Quality-of-Life Assessment: Ancillary studies
Cardiac disorders Cardiac disorders	8.3% 2/24 • Number of events 4 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Endocrine disorders Endocrine disorders	4.2% 1/24 • Number of events 1 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Eye disorders Eye disorders	25.0% 6/24 • Number of events 8 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Gastrointestinal disorders Gastrointestinal disorders	91.7% 22/24 • Number of events 95 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
General disorders General disorders and administration site conditions	54.2% 13/24 • Number of events 29 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Infections and infestations Infections and infestations	41.7% 10/24 • Number of events 24 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	20.8% 5/24 • Number of events 16 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Investigations Investigations	37.5% 9/24 • Number of events 20 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Metabolism and nutrition disorders Metabolism and nutrition disorders	37.5% 9/24 • Number of events 15 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	62.5% 15/24 • Number of events 39 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Nervous system disorders Nervous system disorders	66.7% 16/24 • Number of events 40 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Psychiatric disorders Psychiatric disorders	29.2% 7/24 • Number of events 11 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Renal and urinary disorders Renal and urinary disorders	12.5% 3/24 • Number of events 4 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	66.7% 16/24 • Number of events 49 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	29.2% 7/24 • Number of events 9 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Surgical and medical procedures Surgical and Medical Procedure	4.2% 1/24 • Number of events 1 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Vascular disorders Vascular disorders	8.3% 2/24 • Number of events 2 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.
Blood and lymphatic system disorders Blood and lymphatic system disorders	50.0% 12/24 • Number of events 40 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.	— 0/0 • 6 years No participants were enrolled in Arm II - Arm IV.