ATM Gene Mutation, ATR Gene Mutation, BARD1 Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CHEK1 Gene Mutation, CHEK2 Gene Mutation, FANCA Gene Mutation, FANCC Gene Mutation, FANCD2 Gene Mutation, FANCF Gene Mutation, FANCM Gene Mutation, NBN Gene Mutation, PALB2 Gene Mutation, RAD51B Gene Mutation, RAD51 Gene Mutation, RAD54L Gene Mutation, Recurrent Squamous Cell Lung Carcinoma, RPA1 Gene Mutation, Stage IV Squamous Cell Lung Carcinoma AJCC v7
Conditions
Brief summary
This phase II trial studies how well talazoparib works in treating patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer that has come back after previous treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the overall response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib (BMN 673) in HRRD Medivation (MDVN)-positive patients. SECONDARY OBJECTIVES: I. To evaluate investigator assessed progression-free survival (IA-PFS) and overall survival (OS) associated with therapy in HRRD MDVN-positive patients. II. To evaluate ORR, IA-PFS, and OS in HRRD Foundation Medicine, Inc. (FMI)-positive patients. III. To evaluate ORR in HRRD MDVN-negative/HRRD FMI-positive patients. IV. To evaluate the frequency and severity of toxicities associated with talazoparib (BMN 673) in HRRD FMI-positive patients. TERTIARY OBJECTIVES: I. To assess if the homologous recombination deficiency (HRD) score is associated with clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated with talazoparib (BMN 673). II. To assess if the level of PARP protein expression determined by immunohistochemistry is associated with clinical outcomes (response, PFS, OS) in HRRD FMI-positive patients treated with talazoparib (BMN 673). III. To characterize pharmacokinetic properties of talazoparib (BMN 673). OUTLINE: Patients receive talazoparib orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and at the end of year 3.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
DRUGTalazoparib
Given PO
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) * Patients must be assigned to S1400G; S1400G biomarker eligibility defined as homologous recombination repair deficiency (HRRD) positive is as follows * Biomarker-positive group * HRRD by FMI * Homologous recombination repair deficiency by Foundation Medicine Inc., criteria * Alteration type * Truncating mutation, frameshift deletions, indels missense and nonsense mutations predicted to have functional consequence in any of the specified genes * Eligible alteration * Mutation in any one of the following critical HRR pathway genes: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1 * Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib \[BMN 673\]) as its primary pharmacology * Patients must have achieved stable disease, a partial response, or a complete response at their first disease assessment after initiating first-line platinum-based chemotherapy; patients determined to have progressed (in the opinion of the treating physician) at their first disease assessment are not eligible * Patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of talazoparib (BMN 673) (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or active peptic ulcer disease); patients must not have active small or large intestine inflammation such as Crohn's disease or ulcerative colitis (within 12 months of sub-study registration) * Patients must be able to take oral medications; patients must be able to swallow capsules whole without crushing or altering them in any way * Patients must not be taking, nor plan to take while on protocol treatment strong P-glycoprotein (P-gp) inhibitors, P-gp inducers, or breast cancer resistance protein (BCRP) inhibitors; the language ?P-gp or BCRP inhibitors or inducers? is reworded to ?strong P-gp inhibitors, P-gp inducers, or BCRP inhibitors? for consistency with the investigator brochure * Patients must agree to have blood specimens submitted for pharmacokinetic analysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants | Up to 3 years post sub-study registration | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). With 40 HRRD subset positive patients, overall response rate can be estimated within 13% with 95% confidence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants | Up to 3 years post sub-study registration | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment. Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). |
| Overall Survival (OS) in HRRD-positive (MDVN) Participants | Up to 3 years post sub-study registration | From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). |
| Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants | 3 years post sub-study registration | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes). |
| Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants | 3 years post sub-study registration | From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment. Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes). |
| Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-negative Per MDVN But HRRD-positive Per FMI Participants | 3 years post sub-study registration | The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed on participants that meet a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc.) but not the stricter definition set by MDVN. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes). |
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow up until death or 3 years post registration | Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| Overall Survival (OS) in HRRD-positive (FMI) Participants | 3 years post sub-study registration | From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using a broad definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes). |
| Duration of Response in HRRD-positive (FMI) Participants | Up to 3 years | From date of documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause among participants who achieve a complete or partial response. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Homologous Recombination Deficiency (HRD) Immunohistochemistry Score | Up to 3 years | A logistic regression model will be used as both a continuous variable and categorized as high versus low. A Cox regression model will be used to assess associations with progression free survival and overall survival. |
| PARP Protein Expression Levels Assessed by Immunohistochemistry | Up to 3 years | A logistic regression model will be used to evaluate if HRD score (as both a continuous variable and categorized as high versus low) and PARP protein expression levels are associated with response. Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival. |
Countries
Canada, United States
Participant flow
Pre-assignment details
51 participants were enrolled. 3 participants were ineligible due to progression on first-line platinum-based chemotherapy or not receiving prior platinum-based chemotherapy and 1 participant died before receiving protocol treatment. Thus, only 47 participants were eligible. Analyses were done for 2 participant populations-: i) eligible HRRD-positive participants per Foundation Medicine Inc. criteria (FMI) - 47 ii) eligible HRRD-positive participants per Medivation (MDVN) criteria - 24
Participants by arm
| Arm | Count |
|---|---|
| Talazoparib Participants receive talazoparib PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Talazoparib: Given PO | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 3 |
| Overall Study | Progression/relapse | 38 |
| Overall Study | Refusal unrelated to adverse events | 1 |
Baseline characteristics
| Characteristic | Talazoparib |
|---|---|
| Age, Continuous | 66.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Number of prior lines of therapy for stage IV disease 0 | 11 Participants |
| Number of prior lines of therapy for stage IV disease 1 | 13 Participants |
| Number of prior lines of therapy for stage IV disease >=2 | 23 Participants |
| Performance status 0 | 10 Participants |
| Performance status 1 | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 39 Participants |
| Smoking status Current smoker | 7 Participants |
| Smoking status Former smoker | 31 Participants |
| Smoking status Never smoker | 1 Participants |
| Smoking status Recent smoker | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 38 / 47 |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 23 / 47 |
Outcome results
Primary
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants
The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes). With 40 HRRD subset positive patients, overall response rate can be estimated within 13% with 95% confidence.
Time frame: Up to 3 years post sub-study registration
Population: Participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib | Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants | 4 percentage of participants |
Secondary
Duration of Response in HRRD-positive (FMI) Participants
From date of documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause among participants who achieve a complete or partial response.
Time frame: Up to 3 years
Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib | Duration of Response in HRRD-positive (FMI) Participants | 1.8 months |
Secondary
Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants
From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment. Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).
Time frame: 3 years post sub-study registration
Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib | Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants | 2.5 months |
Secondary
Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants
From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression were censored at date of last disease assessment. Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes).
Time frame: Up to 3 years post sub-study registration
Population: Eligible participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib | Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants | 2.4 months |
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Duration of treatment and follow up until death or 3 years post registration
Population: Participants who received at least one dose of talazoparib treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 2 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoalbuminemia | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 2 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 6 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound infection | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alanine aminotransferase increased | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 7 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Aspartate aminotransferase increased | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 4 Participants |
| Talazoparib | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 3 Participants |
Secondary
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-negative Per MDVN But HRRD-positive Per FMI Participants
The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed on participants that meet a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc.) but not the stricter definition set by MDVN. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).
Time frame: 3 years post sub-study registration
Population: All eligible participants that meet a broad definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria), but do not meet the more restrictive MDVN criteria for HRRD positivity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib | Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-negative Per MDVN But HRRD-positive Per FMI Participants | 17 percentage of participants |
Secondary
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants
The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with talazoparib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Analysis was performed using a broader definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).
Time frame: 3 years post sub-study registration
Population: All eligible participants that meet a broad definition of homologous recombination repair deficiency (HRRD) -positivity (Foundation Medicine Inc. \[FMI\] criteria).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib | Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants | 11 percentage of participants |
Secondary
Overall Survival (OS) in HRRD-positive (FMI) Participants
From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using a broad definition of homologous recombination repair deficiency (HRRD)-positivity (Foundation Medicine Inc. \[FMI\] criteria; defined by alterations in ATM/ATR/BARD1/BRCA1/BRCA2/BRIP1/CHEK1/CHEK2/FANCA/FANCC/FANCD2/FANCF/FANCM/NBN(NBS1)/PALB2/RAD51/RAD51B(RAD51L1)/RAD54L/RPA1 genes).
Time frame: 3 years post sub-study registration
Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib | Overall Survival (OS) in HRRD-positive (FMI) Participants | 5.7 months |
Secondary
Overall Survival (OS) in HRRD-positive (MDVN) Participants
From date of sub-study registration to date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using a more restricted definition of homologous recombination repair deficiency (HRRD)-positivity (Medivation \[MDVN\] criteria; defined by alterations in ATM/ATR/BRCA1/BRCA2/PALB2 genes).
Time frame: Up to 3 years post sub-study registration
Population: Participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib | Overall Survival (OS) in HRRD-positive (MDVN) Participants | 5.2 months |
Other Pre-specified
Homologous Recombination Deficiency (HRD) Immunohistochemistry Score
A logistic regression model will be used as both a continuous variable and categorized as high versus low. A Cox regression model will be used to assess associations with progression free survival and overall survival.
Time frame: Up to 3 years
Other Pre-specified
PARP Protein Expression Levels Assessed by Immunohistochemistry
A logistic regression model will be used to evaluate if HRD score (as both a continuous variable and categorized as high versus low) and PARP protein expression levels are associated with response. Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.
Time frame: Up to 3 years