Trial Outcomes & Findings for Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer (NCT NCT03377556)

NCT ID: NCT03377556

Last Updated: 2021-06-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 51 participants
• Primary outcome timeframe: Up to 3 years post sub-study registration
• Results posted on: 2021-06-23

Participant Flow

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

Participant milestones

Measure	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
Overall Study STARTED	47
Overall Study Primary Analysis Population (HRRD-positive Per MDVN Criteria)	24
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	47

Reasons for withdrawal

Measure	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
Overall Study Adverse Event	5
Overall Study Refusal unrelated to adverse events	1
Overall Study Progression/relapse	38
Overall Study Death	3

Baseline Characteristics

Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer

Baseline characteristics by cohort

Measure	Talazoparib n=47 Participants 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
Age, Continuous	66.7 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 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	7 Participants n=5 Participants
Race (NIH/OMB) White	40 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
Performance status 0	10 Participants n=5 Participants
Performance status 1	37 Participants n=5 Participants
Number of prior lines of therapy for stage IV disease 0	11 Participants n=5 Participants
Number of prior lines of therapy for stage IV disease 1	13 Participants n=5 Participants
Number of prior lines of therapy for stage IV disease >=2	23 Participants n=5 Participants
Smoking status Current smoker	7 Participants n=5 Participants
Smoking status Recent smoker	8 Participants n=5 Participants
Smoking status Former smoker	31 Participants n=5 Participants
Smoking status Never smoker	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 years post sub-study registration

Population: Participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)

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.

Outcome measures

Measure	Talazoparib n=24 Participants 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
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (MDVN) Participants	4 percentage of participants Interval 0.0 to 21.0

SECONDARY outcome

Timeframe: Up to 3 years post sub-study registration

Population: Eligible participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)

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).

Outcome measures

Measure	Talazoparib n=24 Participants 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
Investigator-assessed Progression-free Survival (IA-PFS) in HRRD-positive (MDVN) Participants	2.4 months Interval 1.5 to 2.8

SECONDARY outcome

Timeframe: Up to 3 years post sub-study registration

Population: Participants that meet the MDVN criteria for homologous recombination repair deficiency (HRRD)

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).

Outcome measures

Measure	Talazoparib n=24 Participants 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
Overall Survival (OS) in HRRD-positive (MDVN) Participants	5.2 months Interval 4.0 to 10.0

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Measure	Talazoparib n=47 Participants 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
Overall Response Rate Assessed by Response Evaluation Criteria in Solid Tumors 1.1 in HRRD-positive (FMI) Participants	11 percentage of participants Interval 4.0 to 23.0

SECONDARY outcome

Timeframe: 3 years post sub-study registration

Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)

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).

Outcome measures

Measure	Talazoparib n=47 Participants 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
Investigator-assessed Progression Free Survival (IA-PFS) FEP in HRRD-positive (FMI) Participants	2.5 months Interval 1.6 to 3.0

SECONDARY outcome

Timeframe: 3 years post sub-study registration

Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)

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).

Outcome measures

Measure	Talazoparib n=47 Participants 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
Overall Survival (OS) in HRRD-positive (FMI) Participants	5.7 months Interval 4.5 to 8.7

SECONDARY outcome

Timeframe: Up to 3 years

Population: All eligible participants that meet the FMI criteria for homologous recombination repair deficiency (HRRD)

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.

Outcome measures

Measure	Talazoparib n=47 Participants 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
Duration of Response in HRRD-positive (FMI) Participants	1.8 months Interval 1.3 to 4.2

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Talazoparib n=23 Participants 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
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 Interval 5.0 to 39.0

SECONDARY outcome

Timeframe: Duration of treatment and follow up until death or 3 years post registration

Population: Participants who received at least one dose of talazoparib treatment.

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.

Outcome measures

Measure	Talazoparib n=47 Participants 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
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	3 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Alanine aminotransferase increased	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Anemia	7 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Aspartate aminotransferase increased	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dehydration	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Generalized muscle weakness	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypertension	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoalbuminemia	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyponatremia	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypotension	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	4 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	6 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Respiratory failure	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Sepsis	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Wound infection	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Talazoparib

Serious events: 23 serious events

Other events: 47 other events

Deaths: 38 deaths

Serious adverse events

Measure	Talazoparib n=47 participants at risk 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
Blood and lymphatic system disorders Anemia	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Cardiac arrest	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Palpitations	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Constipation	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Dysphagia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Esophageal hemorrhage	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Nausea	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Vomiting	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Death NOS	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Fatigue	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Non-cardiac chest pain	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Pain	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Lung infection	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Sepsis	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Platelet count decreased	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Anorexia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Dehydration	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hyponatremia	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Confusion	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Aspiration	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Cough	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Dyspnea	17.0% 8/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Epistaxis	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Hypoxia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Productive cough	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Hypertension	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Hypotension	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs

Other adverse events

Measure	Talazoparib n=47 participants at risk 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
Blood and lymphatic system disorders Anemia	57.4% 27/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Blood and lymphatic system disorders Lymph node pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Atrial fibrillation	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Atrioventricular block first degree	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Cardiac disorders-Other	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Cardiac disorders Sinus tachycardia	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Endocrine disorders Hyperthyroidism	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Eye disorders Dry eye	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Eye disorders Flashing lights	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Abdominal pain	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Constipation	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Diarrhea	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Dry mouth	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Dyspepsia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Dysphagia	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Flatulence	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Gastrointestinal disorders-Other	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Mucositis oral	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Nausea	29.8% 14/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Oral pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Rectal pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Gastrointestinal disorders Vomiting	21.3% 10/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Chills	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Edema limbs	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Fatigue	51.1% 24/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Fever	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Gait disturbance	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders General disorders and admin site conditions - Other	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Localized edema	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Malaise	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Non-cardiac chest pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
General disorders Pain	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Hepatobiliary disorders Hepatic failure	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Infections and infestations-Other	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Lung infection	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Sepsis	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Upper respiratory infection	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Infections and infestations Wound infection	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Injury, poisoning and procedural complications Bruising	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Injury, poisoning and procedural complications Fall	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Alanine aminotransferase increased	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Alkaline phosphatase increased	12.8% 6/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Aspartate aminotransferase increased	10.6% 5/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Blood bilirubin increased	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Cardiac troponin I increased	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Cardiac troponin T increased	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Creatinine increased	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations INR increased	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Investigations-Other	10.6% 5/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Lymphocyte count decreased	29.8% 14/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Neutrophil count decreased	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Platelet count decreased	48.9% 23/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Weight gain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations Weight loss	25.5% 12/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Investigations White blood cell decreased	23.4% 11/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Anorexia	29.8% 14/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Dehydration	10.6% 5/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Glucose intolerance	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypercalcemia	17.0% 8/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hyperglycemia	21.3% 10/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hyperkalemia	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypoalbuminemia	25.5% 12/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypocalcemia	12.8% 6/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypoglycemia	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypokalemia	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypomagnesemia	17.0% 8/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hyponatremia	27.7% 13/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Hypophosphatemia	12.8% 6/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Back pain	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Chest wall pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Flank pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Generalized muscle weakness	12.8% 6/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tiss disorder - Other	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Musculoskeletal and connective tissue disorders Pain in extremity	8.5% 4/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Amnesia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Dizziness	10.6% 5/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Dysgeusia	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Headache	19.1% 9/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Memory impairment	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Peripheral sensory neuropathy	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Nervous system disorders Somnolence	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Anxiety	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Confusion	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Delirium	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Depression	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Psychiatric disorders Insomnia	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Renal and urinary disorders Acute kidney injury	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Renal and urinary disorders Cystitis noninfective	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Renal and urinary disorders Urinary incontinence	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Renal and urinary disorders Urinary retention	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Renal and urinary disorders Urinary tract pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Cough	14.9% 7/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Dyspnea	21.3% 10/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Hypoxia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.3% 2/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Productive cough	10.6% 5/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Sinus disorder	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Respiratory, thoracic and mediastinal disorders Wheezing	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Skin and subcutaneous tissue disorders Alopecia	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Skin and subcutaneous tissue disorders Pruritus	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Skin and subcutaneous tissue disorders Rash maculo-papular	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Hot flashes	2.1% 1/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Hypertension	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Hypotension	12.8% 6/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs
Vascular disorders Thromboembolic event	6.4% 3/47 • Duration of treatment and follow up until death or 3 years post-registration 47 participants that were eligible and received protocol therapy were assessed for AEs

Additional Information

Lung Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: kmini@fredhutch.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place