Trial Outcomes & Findings for Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations (NCT NCT01989546)
NCT ID: NCT01989546
Last Updated: 2021-02-23
Results Overview
Evaluation of drug effect on deoxyribonuclecic acid (DNA) damage response will be performed using immunofluorescence assays to measure the DNA damage repair marker γH2A (the phosphorylated form of histone family member X, H2AX) in the nucleus of tumor cells obtained via core biopsy.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
Cycle 1, day 8
Results posted on
2021-02-23
Participant Flow
Participant milestones
| Measure |
Talazoparib (BMN 673)
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Talazoparib (BMN 673)
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Overall Study
Clinical Progression
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1
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Overall Study
Disease progression on study
|
8
|
Baseline Characteristics
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations
Baseline characteristics by cohort
| Measure |
Talazoparib (BMN 673)
n=9 Participants
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
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5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
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4 Participants
n=5 Participants
|
|
Age, Continuous
|
61.23 years
STANDARD_DEVIATION 12.33 • n=5 Participants
|
|
Sex: Female, Male
Female
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5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
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4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 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
|
8 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
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9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Cycle 1, day 8Evaluation of drug effect on deoxyribonuclecic acid (DNA) damage response will be performed using immunofluorescence assays to measure the DNA damage repair marker γH2A (the phosphorylated form of histone family member X, H2AX) in the nucleus of tumor cells obtained via core biopsy.
Outcome measures
| Measure |
Talazoparib (BMN 673)
n=9 Participants
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Percent of Participants Who Achieve a Sustained Progressive Disease (PD) Response, Defined to be at Least 4% Nuclear Area Positive (NAP) γH2AX at the Day 8 Biopsy
|
44.4 percentage of participants
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SECONDARY outcome
Timeframe: Restaging scans will be carried out every 2 cycles (8 weeks) until the end of treatment (average, 7 months)Response will be evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)1. 1 guidelines; restaging scans will be carried out every 2 cycles. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. And 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). The appearance of one or more new lesions is also considered progressions.
Outcome measures
| Measure |
Talazoparib (BMN 673)
n=9 Participants
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Response Rate (Complete Response (CR) + Partial Response (PR) of Treatment With Talazoparib (BMN 673) in Participants With Deleterious Breast Cancer (BRCA) Mutations
Complete Response
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0 Participants
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Response Rate (Complete Response (CR) + Partial Response (PR) of Treatment With Talazoparib (BMN 673) in Participants With Deleterious Breast Cancer (BRCA) Mutations
Partial Response
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5 Participants
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OTHER_PRE_SPECIFIED outcome
Timeframe: Date treatment consent signed to date off study, approximately 28 months and 24 days.Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Outcome measures
| Measure |
Talazoparib (BMN 673)
n=9 Participants
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
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9 Participants
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Adverse Events
Talazoparib (BMN 673)
Serious events: 3 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Talazoparib (BMN 673)
n=9 participants at risk
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Blood and lymphatic system disorders
Anemia
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Platelet count decreased
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
Other adverse events
| Measure |
Talazoparib (BMN 673)
n=9 participants at risk
Single-agent BMN 673 (talazoparib) dosed orally at 1 mg/day in 28-day cycles. This poly (ADP-ribose) polymerase (PARP) inhibitor has been shown to cause single-agent synthetic lethality in breast cancer 1 and breast cancer 2 (BRCA1/2)- and phosphatase and tensin homolog (PTEN)-deficient cell lines, and has potent antitumor activity in animal models of tumors harboring mutations in deoxyribonucleic acid (DNA) repair pathways.
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|---|---|
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Gastrointestinal disorders
Abdominal pain
|
33.3%
3/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
44.4%
4/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Alkaline phosphatase increased
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Blood and lymphatic system disorders
Anemia
|
66.7%
6/9 • Number of events 33 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
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Metabolism and nutrition disorders
Anorexia
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Bloating
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Creatinine increased
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Diarrhea
|
55.6%
5/9 • Number of events 11 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Nervous system disorders
Dizziness
|
33.3%
3/9 • Number of events 8 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.1%
1/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Edema limbs
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Nervous system disorders
Extrapyramidal disorder
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Eye disorders
Eye disorders - Other, Eye disorder; let eye itching
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Fatigue
|
44.4%
4/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Fever
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Flu like symptoms
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Vascular disorders
Hot flashes
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypernatremia
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Vascular disorders
Hypertension
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
44.4%
4/9 • Number of events 6 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
22.2%
2/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
11.1%
1/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Vascular disorders
Hypotension
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal hemorrhage
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Lymphocyte count decreased
|
88.9%
8/9 • Number of events 32 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Nausea
|
77.8%
7/9 • Number of events 10 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Neutrophil count decreased
|
66.7%
6/9 • Number of events 22 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Oral pain
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
General disorders
Pain
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Cardiac disorders
Palpitations
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Platelet count decreased
|
88.9%
8/9 • Number of events 19 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Rash acneiform
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Renal and urinary disorders
Renal calculi
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, Surgical and medical procedure - Bronchoscopy
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Ear and labyrinth disorders
Tinnitus
|
11.1%
1/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Infections and infestations
Upper respiratory infection
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Renal and urinary disorders
Urinary frequency
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Cardiac disorders
Ventricular arrhythmia
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Gastrointestinal disorders
Vomiting
|
44.4%
4/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
Weight loss
|
33.3%
3/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
|
Investigations
White blood cell decreased
|
88.9%
8/9 • Number of events 38 • Date treatment consent signed to date off study, approximately 28 months and 24 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place