Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial)

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title:

A Phase II Study of Talazoparib Plus Avelumab in Patients With Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer Bearing Pathogenic STK11 Genomic Alterations (LUNG-MAP Sub-Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04173507
• Other study ID #: S1900C
• Secondary ID: NCI-2019-07142S1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 14, 2020
• Est. completion date: July 1, 2024

Study information

• Verified date: May 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II LUNG-MAP treatment trial studies how well combination treatment (talazoparib plus avelumab) works in treating patients with non-squamous non-small cell lung cancer that has an STK11 gene mutation and has come back (recurrent) or is stage IV. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy drugs given as single therapies or in combination with chemotherapy do not appear to work as well in lung cancer cells with mutations in the STK11 gene versus those that do not have the mutation. Adding the medicine talazoparib to the immunotherapy drug avelumab may work better in treating lung cancers that have an STK11 gene mutation.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib plus avelumab in patients with stage IV or recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 genomic alterations that were previously-treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy.

II. To evaluate disease control rate at 12 weeks (DCR12) after registration.

SECONDARY OBJECTIVES:

I. To evaluate investigator assessed progression-free survival (IA-PFS). II. To evaluate overall survival (OS). III. To evaluate duration of response (DOR) among responders. IV. To evaluate the frequency and severity of toxicities.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline, cycle 3 day 1, progression, and end of treatment for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and examine molecular mechanisms of resistance to talazoparib and avelumab.

II. To establish a tissue/blood repository from patients with refractory non-small cell lung cancer (NSCLC).

III. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent somatic mutations in KEAP1 detected on the Foundation Medicine Inc. (FMI) panel from the LUNGMAP screening protocol.

IV. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent mutations in ATM or other DNA damage response genes detected on the FMI panel from the LUNGMAP screening protocol.

V. To evaluate the association between tumor mutational burden (TMB) measured on the FMI panel from the LUNGMAP screening protocol and clinical outcomes (ORR, IA-PFS, OS).

OUTLINE:

Patients receive talazoparib orally (PO) daily and avelumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up until death or 3 years after sub-study registration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: July 1, 2024
• Est. primary completion date: November 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients must be assigned to S1900C. Assignment to S1900C is determined by the LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900C is based on the identification of a pathogenic somatic mutation in STK11 or STK11 bi-allelic loss on tumor

• Patients must have histologically or cytologically confirmed stage IV or recurrent non-squamous, mixed squamous/non-squamous (e.g., adeno-squamous carcinoma), or non-small cell lung cancer not otherwise specified (NSCLC NOS). Patients with pure squamous cell carcinoma are not eligible

• Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to sub-study registration

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to sub-study registration

• Patients with known human immunodeficiency virus (HIV) infection are eligible, provided they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to sub-study registration

• Patients must have received at least one line of anti-PD-1 or anti-PD-L1 therapy for stage III, IV or recurrent disease. Any number of additional, non-platinum-based chemotherapy or targeted therapy regimens for recurrent or metastatic disease are allowed

• Patients may not have received more than one line of anti-PD-1 or anti-PD-L1 therapy in the Stage IV or recurrent setting. Anti-PD-1 or anti-PD-L1 therapy may have been given alone or in combination with platinum-based chemotherapy, an anti-CTLA4 therapy, or other immune-modulatory therapy. Patients must have experienced disease progression > 42 days following initiation (cycle 1 day 1) of the anti-PD-1 or anti-PD-L1 containing regimen

• Patients who did not receive anti-PD-1 or anti-PD-L1 therapy in combination with platinum-based chemotherapy, must have also received prior platinum-based chemotherapy and experienced disease progression > 42 days following initiation (cycle 1 day 1) of platinum based chemotherapy

• Patients who received anti-PD-1 or anti-PD-L1 therapy following concurrent chemoradiation for stage III disease as their only line of anti-PD-1 or anti-PD-L1 therapy, are eligible if they experienced disease progression less than (<) 365 days from the date of initiation of anti-PD-1 or anti-PD-L1 therapy

• Patients who received prior adjuvant platinum-based therapy post-surgical resection for stage I-III disease (i.e. the patient has not received platinum-based chemotherapy for Stage IV or recurrent disease) must have had disease progression during or after platinum-based chemotherapy that occurred less than (<) 365 days from the last date that the patient received that therapy

• Patients must be able to swallow capsules whole

• Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib) as its primary pharmacology

• Patients must not be taking, nor plan to take while on protocol treatment strong P-glycoprotein (P-gp) inhibitors (e.g. dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), P-gp inducers (rifampin, ritonavir, tipranavir), or strong breast cancer resistance protein (BCRP) inhibitors (e.g. elacridar)

• Patients must have progressed following their most recent line of therapy

• Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration. Patients must have recovered (=< grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration

• Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable

• Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to sub-study registration. CT and MRI scans must be submitted for central review via Transfer of Images and Data (TRIAD)

• Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration. Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to sub-study registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration

• Patient must not have had a major surgery within 14 days prior to sub-study registration. Patient must have fully recovered from the effects of prior surgery in the opinion of the treating investigator

• Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x IULN

• Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN within 28 days prior to sub-study registration (if both ALT and AST are done, both must be =< 2 IULN). For patients with liver metastases, either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)

• Patients must have a serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration

• Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration

• Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia

• Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years

• Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

• Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

• Hemoglobin >= 9 g/dL (obtained within 28 days prior to sub-study registration). Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to sub-study registration)

• Patients must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)

• Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens

Exclusion Criteria:

• Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• Patients must not have a history of prior organ transplantation, including allogeneic stem-cell transplantation

• Patients must not have received systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 7 days prior to sub-study registration. Inhaled or topical steroids, and adrenal replacement doses =< 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease

• Patients must not have active autoimmune disease that requires systemic steroids (equivalent of > 10 mg of prednisone) or immunosuppressive agents within 7 days prior to sub-study registration (for example disease-modifying anti-rheumatic drugs). Exceptions include: patients with controlled type 1 diabetes mellitus, controlled hypo- or hyperthyroidism, vitiligo, resolved childhood asthma/atopy, or psoriasis not requiring immunosuppressive therapy

• Patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of talazoparib (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 prior to sub-study registration

• Patients must not have known prior or suspected hypersensitivity to monoclonal antibodies (grade >= 3)

• Patients must not have any history of anaphylaxis or uncontrolled asthma. Uncontrolled asthma is defined as a patient having any one of the following criteria:

• Poor symptom control: Asthma Control Questionnaire (ACQ) consistently > 1.5 or Asthma Control Test Questionnaire (ACT) < 20 (or "not well controlled" by National Asthma Education and Prevention Program [NAEPP] or Global Initiative for Asthma [GINA] guidelines over the 3 months or evaluation)

• Frequent severe exacerbations: 2 or more bursts of systemic corticosteroids (CSs) (> 3 days each) in the previous year

• Serious exacerbations: at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year

• Airflow limitation: Forced expiratory volume in 1 second (FEV1) < 80% predicted (in the presence of reduced FEV1/forced vital capacity [FVC] defined as less than the normal lower limit) following a withhold of both short- and long-acting bronchodilators

• Patients must not have experienced any immune related adverse event, including pneumonitis that led to permanent discontinuation of prior immunotherapy and/or required prolonged high dose of steroids

• Patients must not have evidence of active infection requiring systemic therapy

• Patients must not have received any live attenuated vaccinations within 28 days prior to sub-study registration

Related Conditions & MeSH terms

• Advanced Lung Non-Squamous Non-Small Cell Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrence
• Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8

Intervention

Drug:
• Avelumab
Given IV
• Talazoparib
Given PO
• Talazoparib Tosylate
Given PO

Locations

Country	Name	City	State
United States	Hawaii Cancer Care - Savio	'Aiea	Hawaii
United States	Presbyterian Kaseman Hospital	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Duluth Clinic Ashland	Ashland	Wisconsin
United States	University Cancer and Blood Center LLC	Athens	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	University of Colorado Hospital	Aurora	Colorado
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	McFarland Clinic PC-Boone	Boone	Iowa
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Northeast Georgia Medical Center Braselton	Braselton	Georgia
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	IHA Hematology Oncology Consultants-Canton	Canton	Michigan
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Geauga Hospital	Chardon	Ohio
United States	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Kootenai Medical Center	Coeur d'Alene	Idaho
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Western Maryland Regional Medical Center	Cumberland	Maryland
United States	Genesis Cancer Care Institute	Davenport	Iowa
United States	Genesis Medical Center - East Campus	Davenport	Iowa
United States	Iowa Cancer Specialists	Davenport	Iowa
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Essentia Health - Deer River Clinic	Deer River	Minnesota
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Bayhealth Hospital Kent Campus	Dover	Delaware
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Northside Hospital - Duluth	Duluth	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Kaiser Permanente-Fontana	Fontana	California
United States	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Essentia Health Hibbing Clinic	Hibbing	Minnesota
United States	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	McFarland Clinic PC-Jefferson	Jefferson	Iowa
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Sparrow Hospital	Lansing	Michigan
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at Oakey	Las Vegas	Nevada
United States	Northside Hospital - Gwinnett	Lawrenceville	Georgia
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Bayhealth Hospital Sussex Campus	Milford	Delaware
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho
United States	Yale University	New Haven	Connecticut
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Licking Memorial Hospital	Newark	Ohio
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Kaiser Permanente-Riverside	Riverside	California
United States	University of Rochester	Rochester	New York
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Salem Hospital	Salem	Oregon
United States	Salina Regional Health Center	Salina	Kansas
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Essentia Health Sandstone	Sandstone	Minnesota
United States	North Coast Cancer Care	Sandusky	Ohio
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Genesis Cancer Center - Silvis	Silvis	Illinois
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Suburban Hematology Oncology Associates - Snellville	Snellville	Georgia
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Prisma Health Cancer Institute - Spartanburg	Spartanburg	South Carolina
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Moffitt Cancer Center	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Essentia Health Virginia Clinic	Virginia	Minnesota
United States	Virtua Voorhees	Voorhees	New Jersey
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Veterans Affairs Connecticut Healthcare System-West Haven Campus	West Haven	Connecticut
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Cleveland Clinic-Weston	Weston	Florida
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Metro Health Hospital	Wyoming	Michigan
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Percentage of participants with confirmed or unconfirmed, complete or partial response to treatment with talazoparib plus avelumab per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.; Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as baseline.; Partial Response (PR): Applies only to participants with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.	From date of registration to progression or treatment discontinuation, up to 1 year and 9 months
Primary	Disease Control Rate at 12 Weeks (DCR12)	Percentage of participants with a best response of Complete Response (CR), Partial Response (PR), Unconfirmed Partial Response (UPR), or Unconfirmed Complete Response (UCR) by/at the second disease assessment at 12 weeks after registration (+/- 2 weeks), or stable disease at 12 weeks after registration (+/- 2 weeks). Participants with missing or delayed disease assessment at 12 weeks (+/- 2 weeks), at or before the disease assessment at 20 weeks (+/- 2 weeks) with documented lack of progression (CR, PR, UPR, UCR, or stable) were coded as having disease control at 12 weeks. Participants not known to have disease control at 12 weeks who have at least 12 weeks of follow-up were coded as not having disease control at 12 weeks.	12 weeks after registration
Secondary	Investigator-Assessed Progression-Free Survival (IA-PFS)	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 are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) is used as the date of progression.; Progression is defined as: 20% increase in the sum of appropriate diameters of target lesions and absolute increase of at least 0.5 cm, or unequivocal progression of non-measurable disease, or appearance of any new lesion/site, or death from disease without prior documentation of progression or symptomatic deterioration.; Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.	From date of registration to a maximum of 3 years or death
Secondary	Overall Survival (OS)	From date of sub-study registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.	From date of registration to a maximum of 3 years or death
Secondary	Duration of Response (DOR)	From date of first response to first progression assessed by local review or symptomatic deterioration, or death among patients with a response (CR or PR). Those last known to be alive without progression are censored at date of last disease assessment. For those with a missing scan whose next scan shows progression, expected date of the first missing scan is used as progression date.; Complete Response (CR): Disappearance of all target and non-target lesions. No new lesions or disease related symptoms. Lymph nodes must have reduction in short axis to < 1.0cm. Assessed using same technique as baseline.; Partial Response (PR): At least 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Assessed using same technique as baseline.; Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment w/o objective evidence of progression.	From date of registration to a maximum of 3 years or death
Secondary	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for routine toxicity reporting and serious adverse events (SAEs).	Duration of treatment and follow up until death or 3 years post registration