Trial Outcomes & Findings for BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment (NCT NCT02326844)

Last Updated: 2020-08-18

Results Overview

Objective response (complete response (CR) + partial response (PR)) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Every 2 cycles, an average of 64 days

Results posted on

2020-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Ovarian Cancer Patients Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ovarian Cancer Patients n=3 Participants Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	51.1 years STANDARD_DEVIATION 3.45 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 2 cycles, an average of 64 days

Outcome measures

Outcome measures
Measure	Ovarian Cancer Patients n=3 Participants Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Objective Response (Complete Response (CR) + Partial Response (PR))	0 Participants

SECONDARY outcome

Timeframe: 15 months

Here is the number participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events v4.0. For a detailed list of events, see the adverse event module.

Outcome measures

Outcome measures
Measure	Ovarian Cancer Patients n=3 Participants Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Number of Participants With Serious and Non-serious Adverse Events	3 Participants

SECONDARY outcome

Timeframe: 3 months

Duration of response is the time between study enrollment and off-treatment date.

Outcome measures

Outcome measures
Measure	Ovarian Cancer Patients n=3 Participants Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Duration of Response	2 months Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 3 months

Population: This outcome measure was not done because the study was prematurely closed by the Cancer Therapy Evaluation Program (CTEP) sponsor following the enrollment of 3 subjects. We were unable to analyze biomarker endpoints due to insufficient number of samples after premature closure of the study.

The median time to progression after receiving BMN673 will be compared informally to the time of progression for the same patients after receiving an initial PARPi exposure. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more lesions is also considered progressions).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: Data was collected but was not analyzed given lack of statistical value of using only 3 samples and no follow up data.

Patients will undergo a mandatory biopsy at baseline and reverse phase protein microarray (RPPA)26 testing will be performed to determine the potential predictive biomarkers of subsequent poly (adenosine diphosphate \[ADP\]) ribose polymerase inhibitors (PARPi ) response.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: Data was collected but was not analyzed given lack of statistical value of using only 3 samples and no follow up data.

Patients will undergo a mandatory biopsy at baseline and Next Generation Sequencing to elucidate the secondary mutations of BRCA1 and BRCA2 will be performed.

Outcome measures

Outcome data not reported

Adverse Events

Ovarian Cancer Patients

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ovarian Cancer Patients n=3 participants at risk Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Investigations Platelet Count Decreased	33.3% 1/3 • Number of events 5 • 15 months

Other adverse events

Other adverse events
Measure	Ovarian Cancer Patients n=3 participants at risk Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy BMN 673 (talazoparib): 1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Number of events 6 • 15 months
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • 15 months
Investigations Creatinine increased	33.3% 1/3 • Number of events 1 • 15 months
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • 15 months
General disorders Fatigue	66.7% 2/3 • Number of events 2 • 15 months
Respiratory, thoracic and mediastinal disorders Hyperhidrosis	33.3% 1/3 • Number of events 1 • 15 months
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Number of events 1 • 15 months
Investigations Lymphocyte count decreased	33.3% 1/3 • Number of events 2 • 15 months
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • 15 months
Investigations Platelet count decreased	33.3% 1/3 • Number of events 5 • 15 months
Renal and urinary disorders Urinary frequency	33.3% 1/3 • Number of events 1 • 15 months
Vascular disorders Vascular disorders - Other, bleeding gums	33.3% 1/3 • Number of events 1 • 15 months
Investigations White blood cell decreased	33.3% 1/3 • Number of events 4 • 15 months

Additional Information

Dr. Jung-Min Lee

National Cancer Institute

Phone: 301-443-7735

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place