Complete Response, Epithelial Ovarian Cancer, Fallopian Tube Cancer, FIGO Stage III-IV, Newly Diagnosed, Partial Response, Primary Peritoneal
Conditions
Keywords
PARP inhibitor, PARPi, HRD, ATHENA, homologous recombination, DNA repair, LOH, DNA defect, DNA anomaly, Rucaparib, Nivolumab, PD-1, Immuno-, oncology, Tumor, mutational, burden, BRCA, First-line, Primary Therapy, Primary Treatment
Brief summary
This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment following response to front-line treatment in newly diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
Interventions
DRUGRucaparib
Oral rucaparib will be administered twice daily
DRUGNivolumab
IV nivolumab will be administered once every 4 weeks
DRUGPlacebo Oral Tablet
Placebo tablets will be administered twice daily
IV placebo will be administered once every 4 weeks
Sponsors
Bristol-Myers Squibb
Gynecologic Oncology Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Foundation Medicine
pharmaand GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-Blind; only the safety cohort will be open label.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. * Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking) * Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator * Sufficient tumor tissue for planned analysis * ECOG performance status of 0 or 1 * Patients must be 20 years of age to consent in Japan, Taiwan and South Korea; in all other participating countries patients must be 18 years of age to consent
Exclusion criteria
* Pure sarcomas or borderline tumors or mucinous tumors * Active second malignancy * Known central nervous system brain metastases * Any prior treatment for ovarian cancer, other than the first-line platinum regimen * Evidence of interstitial lung disease or active pneumonitis * Active, known or suspected autoimmune disease * Condition requiring active systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS) | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | PFS by investigator was defined as the time from randomization to disease progression, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Monotherapy Arm B and Arm D: Investigator Assessed PFS | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Combination Therapy Arm A and Arm B: Investigator Assessed PFS | From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) | PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Monotherapy Arm B and Arm D: BICR PFS | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Combination Therapy Arm A and Arm B: BICR PFS | From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) | PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Monotherapy Arm B and Arm D: Overall Survival (OS) | From randomization until death due to any cause (up to the primary data analysis at approximately 36 months) | OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause. |
| Monotherapy Arm B and Arm D: OS | From randomization until death due to any cause (up to the primary data analysis at approximately 40 months) | OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause. |
| Combination Therapy Arm A and Arm B: OS | From randomization until death due to any cause (up to the combination therapy interim analysis at approximately 72 months) | OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause. |
| Monotherapy Arm B and Arm D: Objective Response Rate (ORR) | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | ORR was defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Monotherapy Arm B and Arm D: ORR | From randomization until disease progression (up to the primary data analysis at approximately 39 months) | ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Combination Therapy Arm A and Arm B: ORR | From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months) | ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Monotherapy Arm B and Arm D: Duration of Response (DOR) | From first confirmed response until disease progression (up to the primary data analysis at approximately 30 months) | DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of progressive disease (PD) or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Monotherapy Arm B and Arm D: DOR | From first confirmed response until disease progression (up to the primary data analysis at approximately 33 months) | DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
| Combination Therapy Arm A and Arm B: DOR | From first confirmed response until disease progression (up to the combination therapy interim analysis at approximately 60 months) | DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s). |
Countries
Australia, Belgium, Canada, Czechia, Denmark, Finland, Germany, Greece, Ireland, Israel, Italy, Japan, New Zealand, Poland, Romania, Russia, Singapore, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Enrollment is complete and the study is ongoing. Data are presented here for the primary endpoint analysis.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Rucaparib + Nivolumab Participants received oral rucaparib tablets twice daily and nivolumab IV infusion once every 4 weeks. | 436 |
| Arm B: Rucaparib + Placebo Participants received oral rucaparib tablets twice daily and placebo IV infusion once every 4 weeks. | 427 |
| Arm C: Placebo + Nivolumab Participants received oral placebo tablets twice daily and nivolumab IV infusion once every 4 weeks | 108 |
| Arm D: Placebo + Placebo Participants received oral placebo tablets twice daily and placebo IV infusion once every 4 weeks. | 111 |
| Japanese Open-label Safety Cohort: Rucaparib + Nivolumab Participants received oral rucaparib tablets twice daily and nivolumab IV infusion once every 4 weeks. | 15 |
| Total | 1,097 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Ongoing in Long-Term Follow-up (Alive) | 184 | 194 | 46 | 45 | 0 |
Baseline characteristics
| Characteristic | Arm A: Rucaparib + Nivolumab | Arm B: Rucaparib + Placebo | Arm C: Placebo + Nivolumab | Arm D: Placebo + Placebo | Japanese Open-label Safety Cohort: Rucaparib + Nivolumab | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 155 Participants | 157 Participants | 36 Participants | 43 Participants | 2 Participants | 393 Participants |
| Age, Categorical Between 18 and 65 years | 281 Participants | 270 Participants | 72 Participants | 68 Participants | 13 Participants | 704 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 17 Participants | 1 Participants | 1 Participants | 0 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 405 Participants | 397 Participants | 102 Participants | 107 Participants | 14 Participants | 1025 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 13 Participants | 5 Participants | 3 Participants | 1 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 81 Participants | 80 Participants | 22 Participants | 16 Participants | 15 Participants | 214 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 5 Participants | 1 Participants | 3 Participants | 0 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 8 Participants | 2 Participants | 2 Participants | 0 Participants | 31 Participants |
| Race (NIH/OMB) White | 325 Participants | 328 Participants | 83 Participants | 87 Participants | 0 Participants | 823 Participants |
| Sex: Female, Male Female | 436 Participants | 427 Participants | 108 Participants | 111 Participants | 15 Participants | 1097 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 410 | 20 / 448 | 4 / 107 | 2 / 111 | 0 / 15 |
| other Total, other adverse events | 406 / 410 | 433 / 448 | 99 / 107 | 103 / 111 | 15 / 15 |
| serious Total, serious adverse events | 154 / 410 | 117 / 448 | 18 / 107 | 13 / 111 | 4 / 15 |
Outcome results
Primary
Combination Therapy Arm A and Arm B: Investigator Assessed PFS
PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Population: The ITT population included all randomized participants. Presented here are data from combination comparison arms (Arm A and Arm B).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Combination Therapy Arm A and Arm B: Investigator Assessed PFS | 15.0 months |
| Arm D: Placebo + Placebo | Combination Therapy Arm A and Arm B: Investigator Assessed PFS | 20.2 months |
p-value: 0.003895% CI: [1.08, 1.53]Log Rank
Primary
Monotherapy Arm B and Arm D: Investigator Assessed PFS
PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The ITT population included all randomized participants. Presented here are data for the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Investigator Assessed PFS | 20.2 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Investigator Assessed PFS | 9.2 months |
p-value: <0.000195% CI: [0.4, 0.68]Log Rank
Primary
Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS)
PFS by investigator was defined as the time from randomization to disease progression, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The homologous recombination deficiency (HRD) population consisted of all randomized participants with either a tumor tissue alteration in breast cancer genes (BRCA)1 or BRCA2 (tBRCA) or non-tBRCA high loss of heterozygosity (LOHhigh). Presented here are data for the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS) | 28.7 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS) | 11.3 months |
p-value: 0.000495% CI: [0.31, 0.72]Log Rank
Secondary
Combination Therapy Arm A and Arm B: BICR PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Population: BICR was included as a supportive secondary endpoint in the event that the Investigator-assessed PFS result was positive. In the ATHENA-COMBO statistical analysis plan it was specified that the BICR analysis would only be performed if the primary endpoint of Investigator-assessed PFS was statistically significant. Given that the result was negative and not statistically significant, the analysis of BICR was not performed, thus that data is not available and cannot be provided.
Secondary
Combination Therapy Arm A and Arm B: DOR
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the combination therapy interim analysis at approximately 60 months)
Population: The ITT population included all randomized participants. Presented here are data from the combination comparison arms (Arm A and Arm B). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Combination Therapy Arm A and Arm B: DOR | 13.7 months |
| Arm D: Placebo + Placebo | Combination Therapy Arm A and Arm B: DOR | 27.7 months |
Secondary
Combination Therapy Arm A and Arm B: ORR
ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Population: The ITT population included all randomized participants. Presented here are data from combination comparison arms (Arm A and Arm B). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Combination Therapy Arm A and Arm B: ORR | 25.6 percentage of participants |
| Arm D: Placebo + Placebo | Combination Therapy Arm A and Arm B: ORR | 48.8 percentage of participants |
Secondary
Combination Therapy Arm A and Arm B: OS
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the combination therapy interim analysis at approximately 72 months)
Population: The ITT population included all randomized participants. Presented here are data from combination comparison arms (Arm A and Arm B).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Combination Therapy Arm A and Arm B: OS | 49.4 months |
| Arm D: Placebo + Placebo | Combination Therapy Arm A and Arm B: OS | 58.0 months |
Secondary
Monotherapy Arm B and Arm D: BICR PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The ITT population included all randomized participants. Presented here are data from the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: BICR PFS | 25.9 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: BICR PFS | 9.1 months |
Secondary
Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The HRD population consisted of all randomized participants with either tBRCA or non-tBRCA LOHhigh. Presented here are data from the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS | NA months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS | 9.9 months |
Secondary
Monotherapy Arm B and Arm D: DOR
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the primary data analysis at approximately 33 months)
Population: The ITT population included all randomized participants. Presented here are data from the monotherapy comparison arms (Arm B and Arm D). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: DOR | 22.1 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: DOR | 5.5 months |
Secondary
Monotherapy Arm B and Arm D: Duration of Response (DOR)
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of progressive disease (PD) or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the primary data analysis at approximately 30 months)
Population: The HRD population consisted of all randomized participants with either tBRCA or non-tBRCA LOHhigh. Presented here are data from the monotherapy comparison arms (Arm B and Arm D). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Duration of Response (DOR) | 16.7 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Duration of Response (DOR) | 5.5 months |
Secondary
Monotherapy Arm B and Arm D: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The HRD population consisted of all randomized participants with either tBRCA or non-tBRCA LOHhigh. Presented here are data from the monotherapy comparison arms (Arm B and Arm D). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Objective Response Rate (ORR) | 58.8 percentage of participants |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Objective Response Rate (ORR) | 20.0 percentage of participants |
Secondary
Monotherapy Arm B and Arm D: ORR
ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Population: The ITT population included all randomized participants. Presented here are data from the monotherapy comparison arms (Arm B and Arm D). Here, Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure with measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: ORR | 48.8 percentage of participants |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: ORR | 9.1 percentage of participants |
Secondary
Monotherapy Arm B and Arm D: OS
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the primary data analysis at approximately 40 months)
Population: The ITT population included all randomized participants. Presented here are data from the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: OS | 38.8 months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: OS | NA months |
Secondary
Monotherapy Arm B and Arm D: Overall Survival (OS)
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the primary data analysis at approximately 36 months)
Population: The HRD population consisted of all randomized participants with either tBRCA or non-tBRCA LOHhigh. Presented here are data from the monotherapy comparison arms (Arm B and Arm D).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: Rucaparib + Placebo | Monotherapy Arm B and Arm D: Overall Survival (OS) | NA months |
| Arm D: Placebo + Placebo | Monotherapy Arm B and Arm D: Overall Survival (OS) | NA months |