SNPMiner Trials (Home Page)
Report for Mutation S1400G
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
1 A Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid ?Master Protocol? (S1400). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes a ?non-match? sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of care also with the goal of approval.
NCT02154490 Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7 Drug: Docetaxel Biological: Durvalumab Drug: Erlotinib Hydrochloride Drug: FGFR Inhibitor AZD4547 Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Drug: Palbociclib Other: Pharmacological Study Biological: Rilotumumab Drug: Talazoparib Drug: Taselisib Biological: Tremelimumab MeSH:Carcinoma Lung Neoplasms
HPO:Carcinoma Neoplasm of the lung
S1400G: Patients with tumors positive for homologous recombination repair deficiency receive talazoparib PO daily on days 1-21. --- S1400G ---
Primary Outcomes
Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.
Measure: Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II) Time: 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, assessed up to 18 months since completion of accrualDescription: Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median investigator-assessed progression-free survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified.
Measure: Investigator-assessed progression-free survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy vs standard therapy (Design #2,Phase III,Option for Biomarker-driven sub-studies) Time: Up to 3 yearsDescription: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
Measure: Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase III) Time: 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, assessed up to 18 months since completion of accrualDescription: The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the Phase III component if the objective response rate is at least 25%. Response rates and associated confidence intervals will be calculated.
Measure: Objective response rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II, Option for Biomarker-driven Sub-studies) Time: Up to 3 yearsDescription: Response rates and associated confidence intervals will be calculated.
Measure: Objective response rate (confirmed and unconfirmed, complete and partial) in patients treated with investigational non-match therapy with advanced stage refractory squamous cell carcinoma of the lung (Design #2, Option for Non-Match Sub-Studies) Time: Up to 3 yearsDescription: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
Measure: Overall survival (Design #1, Phase III) Time: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 yearsDescription: The Brookmeyer-Crowley method will be used to calculate confidence intervals for median overall survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified.
Measure: Overall survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) Time: Up to 3 yearsSecondary Outcomes
Description: Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.
Measure: Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) Time: Up to 3 yearsDescription: Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
Measure: Frequency and severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) Time: Up to 3 yearsDescription: Descriptive data will be presented.
Measure: Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III) Time: 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, assessed up to 3 yearsDescription: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
Measure: Overall survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) Time: Up to 3 yearsDescription: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.
Measure: Progression free survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) Time: Up to 3 yearsDescription: Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.
Measure: Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III) Time: Up to 3 yearsDescription: Analysis of response rates will be performed using a chi-square or Fisher?s exact test, as appropriate.
Measure: Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies) Time: Up to 3 yearsDescription: Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.
Measure: Severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies) Time: Up to 3 yearsDescription: Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.
Measure: Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III) Time: Up to 3 yearsOther Outcomes
Description: Descriptive data will be presented.
Measure: Screen success rate, monitored by the percentage of screened patients that register to a therapeutic sub-study Time: Up to 3 yearsDescription: Descriptive data will be presented.
Measure: Treatment arm randomization acceptance rate, monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to (Design #1) Time: Up to 3 years2 A Phase II Study of Talazoparib (BMN 673) in Patients With Homologous Recombination Repair Deficiency Positive Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)
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.
NCT03377556 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 RAD RAD51 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation Recurrent Squamous Cell Lung Carcinoma RPA1 Gene Mutation Stage IV Squamous Cell Lung Carcinoma AJCC v7 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Talazoparib MeSH:Carcinoma Lung Neoplasms
HPO:Carcinoma Neoplasm of the lung
Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.. 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 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 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 RAD RAD51 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation Recurrent Squamous Cell Lung Carcinoma RPA1 Gene Mutation Stage IV Squamous Cell Lung Carcinoma AJCC v7 Carcinoma Lung Neoplasms 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. --- S1400G ---
Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.. 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 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 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 RAD RAD51 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation Recurrent Squamous Cell Lung Carcinoma RPA1 Gene Mutation Stage IV Squamous Cell Lung Carcinoma AJCC v7 Carcinoma Lung Neoplasms 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. --- S1400G --- --- S1400G ---
Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.. 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 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 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 RAD RAD51 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation Recurrent Squamous Cell Lung Carcinoma RPA1 Gene Mutation Stage IV Squamous Cell Lung Carcinoma AJCC v7 Carcinoma Lung Neoplasms 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. --- S1400G --- --- S1400G --- --- S1400G ---
Similarly, a Cox regression model will be used to assess associations with progression free survival and overall survival.. 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 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 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 RAD RAD51 Gene Mutation RAD51B Gene Mutation RAD54L Gene Mutation Recurrent Squamous Cell Lung Carcinoma RPA1 Gene Mutation Stage IV Squamous Cell Lung Carcinoma AJCC v7 Carcinoma Lung Neoplasms 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. --- S1400G --- --- S1400G --- --- S1400G --- --- S1400G ---
Primary Outcomes
Description: Primary analyses will be 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.
Measure: Overall response rate assessed by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2) Time: Up to 3 yearsSecondary Outcomes
Description: Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.
Measure: Duration of response (Design #2) Time: Up to 3 yearsDescription: With 40 HRRD subset positive patients, toxicity rates can be estimated within 16% with 95% confidence. With 60 eligible patients, toxicity rates can be estimated within 13% with 95% confidence.
Measure: Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #2) Time: Up to 3 yearsDescription: Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.
Measure: Median investigator assessed progression-free survival (IA-PFS) (Design #2) Time: Up to 3 yearsDescription: Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals.
Measure: Overall survival (OS) (Design #2) Time: Up to 3 yearsOther Outcomes
Description: 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.
Measure: Homologous recombination deficiency (HRD) immunohistochemistry score Time: Up to 3 yearsDescription: 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.
Measure: PARP protein expression levels assessed by immunohistochemistry Time: Up to 3 years