Advanced High-grade Ovarian Cancer, Triple Negative Breast Cancer
Conditions
Brief summary
This study is designed to evaluate the safety, tolerability, PKharmacokinetic profile and treatment effect of pamiparib in Chinese participants with advanced high-grade ovarian cancer (including fallopian cancer or primary peritoneal cancer) and triple negative breast cancer in phase I, and to evaluate the efficacy and safety of pamiparib in Chinese participants with recurrent epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline breast cancer susceptibility gene 1/gene 2 (BRCA1/2) mutation in phase II.
Interventions
DRUGPamiparib
Pamiparib is provided as oral capsules
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants have voluntarily agreed to participate by giving written informed consent. 2. Age 18 years (including 18 years) on the day of signing informed consent. 3. Participants meet the following eligibility criteria for the corresponding part of the study: 1) In Phase 1 portion: The participants must have a histologically or cytologically confirmed locally advanced or metastatic cancer, either triple-negative breast cancer or epithelial, non-mucinous, high-grade ovarian cancer (including fallopian cancer, or primary peritoneal cancer), for which no effective standard therapy is available. 2\) In Phase 2 portion: Participants who have histologically or cytologically confirmed high-grade epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline BRCA1/2 mutation 4. Participants must have measurable disease as defined per the RECIST, version 1.1. 5\. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Key
Exclusion criteria
1. Participants who have been treated with chemotherapy, biologic therapy, immunotherapy, investigational agent, anti-cancer Chinese medicine, or anticancer herbal remedies ≤ 14 days (or ≤5 half-lives, whichever is shorter) prior to starting study drug, or who have not adequately recovered from the side effects of such therapy. 2. Participants who have undergone major surgery for any cause ≤ 4 weeks prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. 3. Participants who have undergone radiotherapy for any cause ≤ 14 days prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. 4. Untreated and/or active brain metastases. 5. Prior therapies targeting poly (ADP-ribose) polymerase (PARP). NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | From first dose to within 30 days of last dose of pamiparib (approximately 36 months) | A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment). |
| Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | From first dose to within 30 days of last dose of pamiparib (approximately 36 months) | — |
| Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC) | Up to approximately 2 years and 8 months | ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Apparent Clearance (CL/F) | Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F) | Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1 | Up to approximately 36 months | ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) |
| Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1 | Up to approximately 36 months | DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD) |
| Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1 | Up to approximately 36 months | CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks |
| Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1 | Up to approximately 36 months | DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first |
| Phase I : Progression Free Survival (PFS) | Up to approximately 36 months | PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first |
| Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1 | Up to approximately 3 years and 8 months | ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response |
| Phase 2: Disease Control Rate by Investigator Per RECIST v1.1 | Up to approximately 3 years and 8 months | DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD) |
| Phase I: Maximum Observed Plasma Concentration (Cmax) | Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria | Up to approximately 3 years and 8 months | CA-125 response is defined the percentage of participants with at least 50% reduction in CA-125 levels from pre-treatment sample |
| Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1 | Up to approximately 3 years and 8 months | DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first |
| Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1 | Up to approximately 3 years and 8 months | PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first |
| Phase 2: Overall Survival (OS) as Assessed by Investigator | Up to approximately 3 years and 8 months | OS is defined as time from the first dose of study medication to the date of death due to any cause |
| Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events | From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months) | A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment). All clinically significant abnormalities in physical examinations, laboratory tests and ECGs are reported as adverse events (AE) in the AE section. |
| Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12) | Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 2: Maximum Observed Plasma Concentration (Cmax) | Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 2: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9) | Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1 | Up to approximately 3 years and 8 months | CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks |
| Phase I: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
| Phase I: Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose | — |
Countries
China
Participant flow
Recruitment details
This study consisted of 2 Phases. Phase 1 (December 2016 to December 2019) in which 15 participants were enrolled and Phase 2 (December 2017 to August 2021) in which 113 participants were enrolled. Primary data cut off date for Phase 1 was 24 December 2019 and Primary cut-off date for Phase 2 was 24 August 2020.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: 20 mg Pamiparib Participants received a single dose of 20 mg pamiparib orally on Day 1 followed by one day treatment free period (Day 2), and 20 mg pamiparib twice a day for the following 21 days (Day 3 to Day 23) until unacceptable toxicities, disease progression, withdrawal of consent, investigator discretion, or delay of treatment due to unresolved toxicities for more than 21 days | 4 |
| Phase 1: 40 mg Pamiparib Participants received a single dose of 40 mg pamiparib orally on Day 1 followed by one day treatment free period (Day 2), and 40 mg pamiparib twice a day for the following 21 days (Day 3 to Day 23) until unacceptable toxicities, disease progression, withdrawal of consent, investigator discretion, or delay of treatment due to unresolved toxicities for more than 21 days | 4 |
| Phase 1: 60 mg Pamiparib Participants received a single dose of 60 mg pamiparib orally on Day 1 followed by a one day treatment free period (Day 2), and 60 mg pamiparib twice a day for the following 21 days (Day 3 to Day 23) until unacceptable toxicities, disease progression, withdrawal of consent, investigator discretion, or delay of treatment due to unresolved toxicities for more than 21 days | 7 |
| Phase 2: 60 mg Pamiparib in PSOC Participants with PSOC received 60 mg pamiparib twice a day on Day 1 of Cycle 1 (21-day cycle) and continuously in all subsequent cycles until occurrence of unacceptable toxicities, disease progression, withdrawal of consent, investigator discretion, or delay of treatment due to unresolved toxicities for more than 21 days | 90 |
| Phase 2: 60 mg Pamiparib in PROC Participants with PROC received 60 mg pamiparib twice a day on Day 1 of Cycle 1 (21-day cycle) and continuously in all subsequent cycles until occurrence of unacceptable toxicities, disease progression, withdrawal of consent, investigator discretion, or delay of treatment due to unresolved toxicities for more than 21 days | 23 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 37 | 18 |
| Overall Study | Disease Progression | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor's Decision | 0 | 0 | 0 | 48 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 5 | 1 |
Baseline characteristics
| Characteristic | Phase 1: 20 mg Pamiparib | Phase 1: 40 mg Pamiparib | Phase 1: 60 mg Pamiparib | Phase 2: 60 mg Pamiparib in PSOC | Phase 2: 60 mg Pamiparib in PROC | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 6.55 | 48.0 years STANDARD_DEVIATION 13.95 | 53.0 years STANDARD_DEVIATION 9.15 | 54.4 years STANDARD_DEVIATION 7.94 | 52.9 years STANDARD_DEVIATION 7.97 | 53.87 years STANDARD_DEVIATION 8.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 7 Participants | 90 Participants | 23 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 4 Participants | 7 Participants | 90 Participants | 23 Participants | 128 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 7 Participants | 90 Participants | 23 Participants | 128 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 | 0 / 4 | 0 / 4 | 0 / 7 | 37 / 90 | 18 / 23 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 7 / 7 | 90 / 90 | 22 / 23 |
| serious Total, serious adverse events | 0 / 4 | 1 / 4 | 2 / 7 | 36 / 90 | 15 / 23 |
Outcome results
Primary
Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs)
Time frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | Physical Findings | 0 Number of participants |
| Phase 1: 20 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | ECGs | 0 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | Physical Findings | 0 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | ECGs | 0 Number of participants |
| Phase 1: 60 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | Physical Findings | 0 Number of participants |
| Phase 1: 60 mg Pamiparib | Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs) | ECGs | 0 Number of participants |
Primary
Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment).
Time frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
Population: Safety Analysis Set includes all participants who received at least one dose of pamiparib
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Participants with at least 1 TEAE | 4 Number of participants |
| Phase 1: 20 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Treatment-Emergent SAEs | 0 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Participants with at least 1 TEAE | 4 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Treatment-Emergent SAEs | 1 Number of participants |
| Phase 1: 60 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Participants with at least 1 TEAE | 7 Number of participants |
| Phase 1: 60 mg Pamiparib | Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Treatment-Emergent SAEs | 2 Number of participants |
Primary
Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC)
ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
Time frame: Up to approximately 2 years and 8 months
Population: Efficacy Evaluable Set defined as all participants in the Safety Analysis Set who had measurable disease at baseline per RECIST v1.1. participants with available data were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC) | 68.3 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC) | 31.6 Percentage of participants |
Secondary
Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: Pharmacokinetic (PK) Analysis Set includes all participants for whom valid pamiparib PK parameters could be estimated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | 1020.5 Hours*nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 43.9 |
| Phase 1: 40 mg Pamiparib | Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | 1912.7 Hours*nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 61.1 |
| Phase 1: 60 mg Pamiparib | Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | 27454.4 Hours*nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 79.4 |
Secondary
Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1
DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)
Time frame: Up to approximately 36 months
Population: Efficacy Evaluable Set includes all participants in the safety analysis set who had the measurable disease at baseline per RECIST v1.1 and had at least one post-baseline tumor assessment unless discontinued due to clinical progression or death prior to assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1 | 50.0 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1 | 50.0 Percentage of participants |
| Phase 1: 60 mg Pamiparib | Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1 | 80.0 Percentage of participants |
Secondary
Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1
DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first
Time frame: Up to approximately 36 months
Population: Efficacy Evaluable Set; Only the number of responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1 | 30.4 months |
| Phase 1: 40 mg Pamiparib | Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1 | NA months |
Secondary
Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set: Participants with at least one available PK parameter at the specified visit were included in the analysis. Phase 2 PK analyses were performed for all Phase 2 participants combined per protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12) | Cycle 1 Day 1 | 16841.5 hours*nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.5 |
| Phase 1: 20 mg Pamiparib | Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12) | Cycle 2 Day 1 | 48802.4 hours*nanograms/milliliter (h*ng/mL) | Geometric Coefficient of Variation 24.3 |
Secondary
Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set: Participants with at least one available PK parameter at the specified visit were included in the analysis. Phase 2 PK analyses were performed for all Phase 2 participants combined per protocol..
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9) | Cycle 1 Day 1 | 13577.2 h*ng/mL | Geometric Coefficient of Variation 20.3 |
| Phase 1: 20 mg Pamiparib | Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9) | Cycle 2 Day 1 | 38259.3 h*ng/mL | Geometric Coefficient of Variation 23.5 |
Secondary
Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria
CA-125 response is defined the percentage of participants with at least 50% reduction in CA-125 levels from pre-treatment sample
Time frame: Up to approximately 3 years and 8 months
Population: CA-125 Evaluable Analysis Set is defined as a subset of participants in the Safety Analysis with baseline CA-125 \>/= 2 X upper limit of normal (ULN)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria | 79.7 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria | 38.1 Percentage of participants |
Secondary
Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1
CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks
Time frame: Up to approximately 3 years and 8 months
Population: Efficacy Analysis Set; Participants with available data were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1 | 73.2 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1 | 52.6 Percentage of participants |
Secondary
Phase 2: Disease Control Rate by Investigator Per RECIST v1.1
DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)
Time frame: Up to approximately 3 years and 8 months
Population: Efficacy Analysis Set; Participants with available data were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Disease Control Rate by Investigator Per RECIST v1.1 | 96.3 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Disease Control Rate by Investigator Per RECIST v1.1 | 78.9 Percentage of participants |
Secondary
Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1
DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first
Time frame: Up to approximately 3 years and 8 months
Population: Efficacy Evaluable Set : Participants with available data were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1 | 11.1 Months |
| Phase 1: 40 mg Pamiparib | Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1 | 6.9 Months |
Secondary
Phase 2: Maximum Observed Plasma Concentration (Cmax)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set: Participants with at least one available PK parameter at the specified visit were included in the analysis. Phase 2 PK analyses were performed for all Phase 2 participants combined per protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Maximum Observed Plasma Concentration (Cmax) | Cycle 1Day 1 | 2275.1 ng/mL | Geometric Coefficient of Variation 19.6 |
| Phase 1: 20 mg Pamiparib | Phase 2: Maximum Observed Plasma Concentration (Cmax) | Cycle 2 Day 1 | 5251.5 ng/mL | Geometric Coefficient of Variation 22.7 |
Secondary
Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events
A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment). All clinically significant abnormalities in physical examinations, laboratory tests and ECGs are reported as adverse events (AE) in the AE section.
Time frame: From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events | Participants With At Least one TEAE | 90 Number of participants |
| Phase 1: 20 mg Pamiparib | Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events | Treatment Emergent SAEs | 36 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events | Participants With At Least one TEAE | 23 Number of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events | Treatment Emergent SAEs | 15 Number of participants |
Secondary
Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1
ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
Time frame: Up to approximately 3 years and 8 months
Population: Efficacy Analysis Set; Participants with available data were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1 | 64.6 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1 | 26.3 Percentage of participants |
Secondary
Phase 2: Overall Survival (OS) as Assessed by Investigator
OS is defined as time from the first dose of study medication to the date of death due to any cause
Time frame: Up to approximately 3 years and 8 months
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Overall Survival (OS) as Assessed by Investigator | 34.1 Months |
| Phase 1: 40 mg Pamiparib | Phase 2: Overall Survival (OS) as Assessed by Investigator | 13.6 Months |
Secondary
Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1
PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first
Time frame: Up to approximately 3 years and 8 months
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1 | 10.4 Months |
| Phase 1: 40 mg Pamiparib | Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1 | 5.5 Months |
Secondary
Phase 2: Time to Reach Cmax (Tmax)
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set: Participants with at least one available PK parameter at the specified visit were included in the analysis. Phase 2 PK analyses were performed for all Phase 2 participants combined per protocol.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase 2: Time to Reach Cmax (Tmax) | Cycle 1 Day 1 | 1.88 hours |
| Phase 1: 20 mg Pamiparib | Phase 2: Time to Reach Cmax (Tmax) | Cycle 2 Day 1 | 1.98 hours |
Secondary
Phase I: Apparent Clearance (CL/F)
Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Apparent Clearance (CL/F) | 1.95 Liters/hour (L/h) | Geometric Coefficient of Variation 43.85 |
| Phase 1: 40 mg Pamiparib | Phase I: Apparent Clearance (CL/F) | 2.07 Liters/hour (L/h) | Geometric Coefficient of Variation 61.09 |
| Phase 1: 60 mg Pamiparib | Phase I: Apparent Clearance (CL/F) | 2.19 Liters/hour (L/h) | Geometric Coefficient of Variation 79.41 |
Secondary
Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F)
Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 34.2 Liters | Geometric Coefficient of Variation 23.6 |
| Phase 1: 40 mg Pamiparib | Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 35.2 Liters | Geometric Coefficient of Variation 21.8 |
| Phase 1: 60 mg Pamiparib | Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F) | 37.2 Liters | Geometric Coefficient of Variation 33.2 |
Secondary
Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1
CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks
Time frame: Up to approximately 36 months
Population: Efficacy Evaluable Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1 | 25.0 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1 | 50.0 Percentage of participants |
| Phase 1: 60 mg Pamiparib | Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1 | 40.0 Percentage of participants |
Secondary
Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1
ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR)
Time frame: Up to approximately 36 months
Population: Efficacy Evaluable Set includes all participants in the safety analysis set who had the measurable disease at baseline per RECIST v1.1 and had at least one post-baseline tumor assessment unless discontinued due to clinical progression or death prior to assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1 | 25.0 Percentage of participants |
| Phase 1: 40 mg Pamiparib | Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1 | 25.0 Percentage of participants |
| Phase 1: 60 mg Pamiparib | Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1 | 0 Percentage of participants |
Secondary
Phase I: Maximum Observed Plasma Concentration (Cmax)
Time frame: Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set was defined as all participants for whom valid PK parameters could be estimated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 1 | 718.4 ng/mL | Geometric Coefficient of Variation 18.9 |
| Phase 1: 20 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 10 | 1280.1 ng/mL | Geometric Coefficient of Variation 70.5 |
| Phase 1: 40 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 1 | 1633.7 ng/mL | Geometric Coefficient of Variation 12.2 |
| Phase 1: 40 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 10 | 5213.8 ng/mL | Geometric Coefficient of Variation 25.6 |
| Phase 1: 60 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 1 | 2302.5 ng/mL | Geometric Coefficient of Variation 30.1 |
| Phase 1: 60 mg Pamiparib | Phase I: Maximum Observed Plasma Concentration (Cmax) | Day 10 | 5861.3 ng/mL | Geometric Coefficient of Variation 29.2 |
Secondary
Phase I : Progression Free Survival (PFS)
PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first
Time frame: Up to approximately 36 months
Population: Safety Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I : Progression Free Survival (PFS) | 2.2 Months |
| Phase 1: 40 mg Pamiparib | Phase I : Progression Free Survival (PFS) | NA Months |
| Phase 1: 60 mg Pamiparib | Phase I : Progression Free Survival (PFS) | 5.6 Months |
Secondary
Phase I: Terminal Elimination Half-life (t1/2)
Time frame: Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Terminal Elimination Half-life (t1/2) | 12.14 hours |
| Phase 1: 40 mg Pamiparib | Phase I: Terminal Elimination Half-life (t1/2) | 11.79 hours |
| Phase 1: 60 mg Pamiparib | Phase I: Terminal Elimination Half-life (t1/2) | 13.77 hours |
Secondary
Phase I: Time to Reach Cmax (Tmax)
Time frame: Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose
Population: PK Analysis Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: 20 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 1 | 1.01 hours |
| Phase 1: 20 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 10 | 1.04 hours |
| Phase 1: 40 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 1 | 0.98 hours |
| Phase 1: 40 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 10 | 1.10 hours |
| Phase 1: 60 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 1 | 1.13 hours |
| Phase 1: 60 mg Pamiparib | Phase I: Time to Reach Cmax (Tmax) | Day 10 | 1.13 hours |