Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Syndrome

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Participants with germline pathogenic or likely pathogenic variants in prostate cancer-related risk genes

Anna C Couvillon, C.R.N.P.

Fatima H Karzai, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

Research studies have shown that genetic changes and family history may increase a man s risk for prostate cancer. Researchers want to follow the prostate health of men who have specific genetic changes associated with prostate cancer to help them learn more about which men are at higher risk for prostate cancer.

Objectives:

To study men with specific genetic changes and determine who is at higher risk for getting prostate cancer. To study if certain genetic changes and family history can be used to help prevent or treat prostate cancer.

Eligibility:

Persons assigned male at birth ages 30-75 who have one or more specific genetic changes but without prostate cancer.

Design:

* This study does not perform genetic testing. All participants must have documented genetic changes and able to provide a copy of the report.
* Before enrollment, participants will provide a copy of documented genetic changes and go through a telephone interview to determine eligibility for the study.
* On enrollment, participants will have medical and family history review, medication review, physical exam, blood collection for clinical and research testing, and MRI (magnetic resonance imaging) of the prostate.
* Every year, participants will repeat the physical exam, medical history, family history, medication review, routine blood tests, including PSA and testosterone.
* Every 2 years, participants will repeat all the above plus prostate MRI and blood tests for research.
* If, at any time, the physical exam, blood tests or MRI are abnormal, participants may be asked to do a biopsy.
* If the biopsy results in prostate cancer, participants will be given counseling on next steps, general treatment recommendations, and then followed with a phone call each year.
* Participants may ask to speak with a genetic counselor.

Background:

Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men.

Prostate cancer has substantial inherited predisposition and certain genetic variants that are associated with an increased risk of prostate cancer.

An evolving approach to prostate cancer screening is to target populations at risk of developing prostate cancer based on their genetic predisposition.

Objective:

To follow the natural history of men with known germline variants or likely pathogenic variants in genes that put them at risk for developing prostate cancer.

Eligibility:

Persons assigned male at birth who are between ages 30-75 years old.

Documented germline pathogenic or likely pathogenic variants in prostate cancer-related risk gene: BRCA 1 and 2, DNA Mismatch Repair (MMR) genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM), HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).

Must be able and willing to provide informed consent.

Design:

Up to 500 subjects will be enrolled.

Participants will undergo sampling of blood for prostate-specific antigen. Based on these results and age, participants will be considered for biopsy and/or continued monitoring if feasible upon clinical discretion.

Participants will undergo a baseline MRI evaluation with follow-up scans every 2 years as clinically indicated.

Following initial evaluation, participants will be followed as clinically indicated, usually at 12 month intervals, to determine their PSA level, prostate cancer treatment (if relevant) and/or disease/survival status until death.

Men at High Genetic Risk for Prostate Cancer

Natural History Study of Men at High Genetic Risk for Prostate Cancer

. All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@ In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

To follow the natural history of men with known germline variants or likely pathogenic variants in genes that put them at high risk for developing prostate cancer

test the feasibility and accuracy of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of local prostate cancer

role of mpMRI in monitoring participants on active surveillance and as a follow up tool for monitoring local disease progression

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Capecitabine

Vinorelbine

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patient will be randomized 2:1 to receive talazoparib oral capsules (1.0 mg) once daily for 21 continuous days

Capecitabine, Eribulin, Gemcitabine or Vinorelbine

Until progression or unacceptable toxicity develops

talazoparib

Physician's-Choice

Pfizer Pfizer CT.gov Call Center

The purpose of this open-label, 2:1 randomized phase III trial is to compare the safety and efficacy of talazoparib (also known as BMN 673) versus protocol-specific physician's choice in patients who have locally advanced and/or metastatic breast cancer with germline BRCA mutations.

A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)

A PHASE 3, OPEN-LABEL, RANDOMIZED PARALLEL,2-ARM,MULTI-CENTER STUDY OF TALAZOPARIB(BMN 673) VERSUS PHYSICIAN'S CHOICE IN GERMLINE BRCA MUTATION SUBJECTS WITH LOCALLY ADVANCED AND/OR METASTATIC BREAST CANCER, WHO HAVE RECEIVED PRIOR CHEMOTHERAPY REGIMENS FOR METASTATIC DISEASE

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

DOR = time from first radiographic documentation of OR (PR or CR) till radiographic disease progression (PD) as per RECIST v1.1 by investigator assessment or to death due to any cause, whichever was first. RECIST 1.1, a) target lesion (TL): CR= disappearance of all non-nodal TL, target lymph nodes reduce to \<10 mm in short axis, PR= at least 30% decrease in sum of diameters of TL, compared to the sum at baseline, PD= at least 20% increase in sum of TL measurements, compared to smallest sum on study including baseline, absolute increase in sum has to be at least 5 mm; b) for non-TL: CR= disappearance of all non-TL, PD= unequivocal progression of non-TL, such that treatment has failed, disease is progressing, regardless of status of TL; c) PD =and/or appearance of \>=1 new lesions. DOR = (earliest date of progression, death, or censoring-date of first documented OR + 1)/30.4375. Analysis was performed by Kaplan-Meier method.

EORTC QLQ-C30: cancer-specific instrument with 30 questions to assess the participant QoL. First 28 questions used to evaluate 5 functional scales (physical, role, cognitive, emotional, social), 3 symptom scales (fatigue, nausea and vomiting, pain) and other single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Each question assessed on 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much); functional scales: higher score = better level of functioning; symptom scale: higher score = more severe symptoms; for single items: higher score= more severe problem. Last 2 questions used to evaluate global health status (GHS)/QoL. Each question was assessed on 7-point scale (1= very poor to 7= excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning. Change from baseline was calculated by subtracting the baseline value from the average value of Week 4 to 160.

TTD in global health status (GHS)/QoL=time (in months) from randomization to the first observation with \>=10 point decrease and no subsequent observations with\<10 point decrease from baseline in GHS/QoL score based on EORTC-QLQ-C30. EORTC QLQ-C30 is a cancer-specific instrument with 30 questions to assess participant quality of life. Question 29 and 30 were used to evaluate GHS/QoL. Each question was assessed on a 7-point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

TTD was defined as the time (in months) from randomization to the first observation with a\>=10 point increase and no subsequent observations with a \<10 point increase from baseline in breast symptom score based on the EORTC-QLQ-BR23. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much), higher scores=high level of symptom/problems.

IRF assessed PFS was defined as time (in months) from randomization until the date of first documented radiologic progressive disease per response evaluation criteria in solid tumors (RECIST) version 1.1 or death from any cause, whichever occurs first. As per RECIST v1.1, progression defined as 1) for target lesions: at least a 20% increase in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), the absolute increase in the sum has to be at least 5 millimeter (mm); 2) for non-target lesions: unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions; 3) and/or appearance of one or more new lesions. The analysis was performed by Kaplan-Meier method.

Investigator assessed objective response was defined as the percentage of participants with a partial response (PR) or complete response (CR) as defined by RECIST v1.1. For target lesions: 1) CR: disappearance of all non-nodal target lesions. Target lymph nodes must reduce to less than 10 mm in short axis. 2) PR: At least a 30% decrease in the sum of diameters of target lesions, compared to the sum at baseline. For non-target lesions, CR: disappearance of all non-target lesions. Percentage of participants with objective response reported are based upon unconfirmed CR/PR.

OS was defined as the time (in months) from randomization to death due to any cause. If death was not observed at the time of study cut-off date or permanently lost to follow-up, OS was censored at the date the participant was last known to be alive on or before the study cut-off date, whichever was earlier. The analysis was performed by Kaplan-Meier method.

A predose PK sample was considered dose-compliant based on the following criteria: A participant must have received 21 consecutive days of 1 mg talazoparib without dosing interruption prior to sample collection; and the predose PK sample must have been collected 24 hours +/- 10 percent (2 hours and 24 minutes) after the previous day's dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection.

An adverse events (AE) was any untoward medical occurrence (e.g., sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug or the day before initiation of a new antineoplastic therapy or 30 days after the date of the last dose date of study drug, whichever occurred first, that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and all non-SAEs.

Toxicity grades were evaluated based on as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). NCI CTCAE v4.03 defined the severity grade as: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death related to AE) for each parameter. Key hematology parameters included hemoglobin (gram per liter \[g/L\]), leukocytes (10\^6 cells per liter), lymphocytes (10\^6 cells per liter), neutrophils (10\^6 cells per liter), and platelets (10\^9 cells per liter). Low value indicated lower values than the baseline values and high value indicated higher values than the baseline values. Only those categories in which at least 1 participant had data were reported.

Toxicity grades were evaluated based on as NCI CTCAE v4.03. NCI CTCAE v4.03 defined the severity grade as: grade 1 (mild), grade 2 (moderate), grade 3 (severe) and grade 4 (potentially life threatening) and grade 5 (death related to AE) for each parameter. Key chemistry parameters included alanine aminotransferase (units per liter), alkaline phosphatase (units per liter), aspartate aminotransferase (units per liter) and bilirubin (micromole per liter). High value indicated higher values than the baseline values and low value indicated lower values than the baseline values. Only those categories in which at least 1 participant had data were reported.

Criteria for potentially clinically significant changes in vital signs included a) Systolic blood pressure: 1) absolute results (AB) greater than (\>) 180 millimeter of mercury (mmHg) and increase from baseline (IFB) greater than or equal to (\>=) 40 mmHg, 2) absolute results less than (\<) 90 mmHg and decrease from baseline (DFB) \>30 mmHg; b) Diastolic blood pressure: 1) absolute results \>110 mmHg and \>=30 mmHg increase from baseline, 2) absolute results \<50 mmHg and \>20 mmHg decrease from baseline 3) \>=20 mmHg increase from baseline; c) Heart rate: 1) absolute results\>120 beats per minute \[bpm\] and \>30 bpm increase from baseline, 2) absolute results \<50 bpm and \>20 bpm decrease from baseline and d) Weight: \>10 percent \[%\] decrease from baseline.

Any medication (other than study drug) which was administered to participants during study after first dose of study drug were considered as concomitant medications.

Medivation, Inc.

Pfizer

Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.

Participants received talazoparib 1 mg, orally, once daily until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician's decision to terminate treatment, or sponsor's decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.

Participants received 1 of the following drugs in specified regimens, as per the physician's choice: 1) capecitabine 1250 mg/m\^2 orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m\^2 (equivalent to eribulin 1.23 mg/ m\^2), as 2 to 5 minute IV infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m\^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m\^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician's decision to terminate treatment, or Sponsor's decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.

Physician's Choice Treatment

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Intent-to-treat (ITT) analysis population included all randomized participants.

Pfizer ClinicalTrials.gov Call Center

Hazard ratio was based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status).

Progression-Free Survival (PFS): Independent Radiological Facility (IRF) Assessment

p-value was based on stratified Cochran-Mantel-Haenszel method. Stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status.

ITT with measurable disease analysis population included all participants in the ITT population who had at least 1 target lesion identified at baseline.

Percentage of Participants With Objective Response: Investigator Assessment

ITT analysis population included all randomized participants.

Overall Survival (OS)

Cycle 2 Day 1: Predose

Cycle 3 Day 1: Predose

Cycle 4 Day 1: Predose

Analysis population included participants who received at least 1 dose of talazoparib and had dose compliant pharmacokinetic (PK) predose sample. Here, "number analyzed" signifies number of participants who were evaluable for the specified categories. This endpoint was not planned to be analyzed for the reporting arm "Physician's Choice Treatment".

Trough Plasma Talazoparib Concentrations

TEAEs

SAEs

Safety analysis population included all participants who received at least 1 dose of any study drug (talazoparib or protocol-specified PCT).

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Hemoglobin: Low value

Leukocytes: Low value

Lymphocytes: Low value

Neutrophils: Low value

Platelets: Low value

Number of Participants With Grade 3 or 4 Post-baseline Toxicities in Laboratory Parameters: Hematology

Alanine Aminotransferase: High Value

Alkaline Phosphatase: High Value

Aspartate Aminotransferase: High Value

Bilirubin: High Value

Number of Participants With Grade 3 or 4 Post-baseline Toxicities in Laboratory Parameters: Chemistry

SBP: AB>180 mmHg and IFB >=40 mmHg

SBP: AB<90 mmHg and DFB >30 mmHg

DBP: AB>110 mmHg and IFB >=30 mmHg

DBP: AB<50 mmHg and DFB>20 mmHg

DBP: IFB>=20 mmHg

Heart rate: AB >120 bpm and IFB >30 bpm

Heart rate: AB <50 bpm and DFB >20 bpm

Weight: >10% DFB

Number of Participants With Potentially Clinically Significant Changes From Baseline in Vital Signs

Number of Participants Taking At-least One Concomitant Medication

Duration of Response (DOR): Investigator Assessment

Analysis was based on repeated measures mixed-effect model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate. Analysis was based on restricted maximum likelihood using unstructured covariance matrix.

Patient-reported outcomes (PRO) evaluable population included all participants who completed the PRO questionnaire at baseline and at least 1 visit post-baseline.

Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at Average Duration Over Week 4 up to Week 160

Hazard ratio is based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system metastasis status).

PRO-evaluable population included all participants who completed the PRO questionnaire at baseline and at least 1 visit post-baseline.

Time to Deterioration (TTD) in Global Health Status/Quality of Life (QOL)

Hazard ratio is based on stratified Cox regression model with treatment as the only covariate (stratification factors: number of prior cytotoxic chemotherapy regimens, triple negative status, history of central nervous system).

Time to Deterioration (TTD) in Breast Symptoms Scale as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)

Participants received talazoparib 1 milligram (mg), orally, once daily until radiographic disease progression as determined by the central independent radiology facility (IRF), unacceptable toxicity, consent withdrawal, physician's decision to terminate treatment, or sponsor's decision to terminate the trial (up to a maximum of 70.2 months). One cycle was of 21 days.

Participants received 1 of the following drugs in specified regimens, as per the physician's choice: 1) capecitabine 1250 milligram per meter square (mg/m\^2) orally twice daily on Day 1 to 14 in each cycle; 2) eribulin mesylate 1.4 mg/m\^2 (equivalent to eribulin 1.23 mg/ m\^2), as 2 to 5 minute intravenous (IV) infusion on Day 1 and 8 in each cycle; 3) gemcitabine 1250 mg/m\^2 as 30-minute IV infusion on Day 1 and 8 in each cycle; 4) vinorelbine 30 mg/m\^2 as 6 to 10 minute IV infusion on Day 1, 8, and 15 in each cycle; until radiographic disease progression as determined by the central IRF, unacceptable toxicity, consent withdrawal, physician's decision to terminate treatment, or Sponsor's decision to terminate the trial (up to a maximum of 45.3 months). One cycle was of 21 days.

Overall Study

Rare Diseases

Carcinoma

Triple Negative Breast Neoplasms

Carcinoma, Renal Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Gastrointestinal Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Irinotecan

Bevacizumab

Fluorouracil

Estrogens

Oxaliplatin

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Pancrelipase

Progesterone

Adenosine

Pancreatin

Tyrosine

600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received ≥ 2 prior systemic regimens including ≥ 1 vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy.

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior poly adenosine diphosphate ribose polymerase (PARP) inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic colorectal cancer (CRC) who received appropriate oxaliplatin or irinotecan- and fluorouracil (5-FU)-based chemotherapy with or without bevacizumab.

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

CB-839

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

Sam Whiting, MD, PhD

This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor CB-839 with the poly adenosine diphosphate ribose polymerase (PARP) inhibitor talazoparib in participants with advanced/metastatic solid tumors.

Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors

A Phase 1b/2 Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor CB-839 in Combination With the PARP Inhibitor Talazoparib in Patients With Advanced or Metastatic Solid Tumors

AEs were grades as assessed by CTCAE v 5.0. A TEAE is defined as any AE occurring on or after the first dose of study drug, or existing events that worsened after the first dose during the study, up to 28 days after the last dose.

An AE is considered "related" if the investigator assessed the relationship as "possibly related" or "probably related." Disease progression includes events in the preferred terms of disease progression and malignant neoplasm progression. Grade 5 disease progression events are excluded from this table.

Hematology parameters conducted included red blood cell (RBC) count, hematocrit, hemoglobin, mean corpuscular volume (MCV), platelet count, white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, performed at the discretion of the investigator. Clinical chemistry parameters included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, albumin, total protein, blood urea nitrogen (BUN), creatinine, sodium, potassium, chloride, calcium, carbon dioxide, glucose, and lactate dehydrogenase (LDH), performed at the discretion of the investigator.

A DLT was defined as an AE determined by the investigator to be possibly or probably related to study drug that also was:

* Any ≥ Grade (Gr) 4 non-hematological toxicity
* Gr 3 non-hematologic toxicity, except: fatigue; nausea/vomiting that responds within 24 hours after initiating maximal supportive care; rash or itching that resolves to ≤ Gr 1 within 2 weeks.
* Any clinically meaningful Gr 3 non-hematologic laboratory value if medical intervention is required OR the abnormality leads to hospitalization, OR the abnormality persists for \> 1 week (except Gr 3/4 elevation in serum amylase and/or lipase not associated with clinical or radiological evidence of pancreatitis).
* Gr ≥ 3 febrile neutropenia
* Gr ≥ 4 anemia; neutropenia lasting \> 7 days; thrombocytopenia
* Gr 3 thrombocytopenia associated with: a bleeding event that requires a platelet transfusion OR a life-threatening bleeding event occurring due to low platelet count which results in urgent intervention.

ORR was defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as the percentage of participants with documented complete response (CR) or partial response (PR) since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease must have been a minimum of 51 days from date of treatment initiation. Exact binomial confidence intervals (Clopper Pearson).

Overall Response Rate is defined by RECIST v1.1 as the percentage of participants with documented confirmed CR or confirmed PR since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been sustained a minimum of 28 days when confirmation was reported. Stable disease must have been a minimum of 51 days from date of treatment initiation. Exact binomial confidence intervals (Clopper Pearson).

Clinical Benefit Rate is defined by RECIST v1.1 as the percentage of participants with documented CR, PR, or stable disease (SD) since the date of treatment initiation. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR or PR must have been sustained a minimum of 28 days when confirmation was reported. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. SD must have been a minimum of 102 days from date of treatment initiation and documented on at least 2 consecutive post-baseline scans. Exact binomial confidence intervals (Clopper Pearson).

PFS was defined as the time from treatment initiation to the date of documented disease progression (PD) within 2 consecutive scheduled radiographic disease assessments or death for any cause, whichever occurs first. PD: ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition, the sum must also demonstrate an absolute increase of ≥ 5 mm. (The appearance of one or more new lesions is also considered progression). Participants with no documentation of PD or death on-study, PD or death occurs after missing 2 consecutive scheduled radiographic disease assessments, or new anti-cancer therapy were censored at the date of last available tumor assessment. Participants missing baseline disease assessments were censored at the date of first dose. Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% CI was used.

Calithera Biosciences, Inc

Per protocol, the serious and nonserious adverse event tables exclude grade 5 disease progression events.

600 mg CB-839 + 1 mg Talazoparib

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic ccRCC who received ≥ 2 prior systemic regimens including ≥ 1 VEGFR TKI therapy.

800 mg CB-839 + 1 mg Talazoparib: ccRCC

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic TNBC ER-, PR-, and HER2-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior PARP inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.

800 mg CB-839 + 1 mg Talazoparib: TNBC

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic CRC who received appropriate oxaliplatin or irinotecan- and 5-FU-based chemotherapy with or without bevacizumab.

800 mg CB-839 + 1 mg Talazoparib: CRC

800 mg CB-839 + 1 mg Talazoparib: Other Histology

American Indian or Alaska Native

Asian

Black or African American

White

Other, Not Specified

Not Reported

Race/Ethnicity, Customized

Study Director

AE grade ≥ 3

AE related to telaglenastat

AE related to talazoparib

AE related to telaglenastat and talazoparib

AE grade ≥ 3 related to telaglenastat

AE grade ≥ 3 related to talazoparib

Safety Analysis Set: all participants who received at least 1 dose of any study-specific treatment (telaglenastat or talazoparib).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Men at High Genetic Risk for Prostate Cancer	NCT03805919	Prostatic Neopl...		30 Years - 75 Years	National Institutes of Health Clinical Center (CC)
A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)	NCT01945775	Breast Neoplasm... BRCA 1 Gene Mut... BRCA 2 Gene Mut...	talazoparib Physician's-Cho...	18 Years -	Pfizer
A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)	NCT01945775	Breast Neoplasm... BRCA 1 Gene Mut... BRCA 2 Gene Mut...	talazoparib Physician's-Cho...	18 Years -	Pfizer
Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors	NCT03875313	Solid Tumor Clear Cell Rena... TNBC - Triple-N... Colorectal Canc... CRC RCC ccRCC	CB-839 Talazoparib	18 Years -	Calithera Biosciences, Inc
Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors	NCT03875313	Solid Tumor Clear Cell Rena... TNBC - Triple-N... Colorectal Canc... CRC RCC ccRCC	CB-839 Talazoparib	18 Years -	Calithera Biosciences, Inc
Pancreatic Cancer Screening for At-risk Individuals	NCT05006131	Pancreatic Canc...	Screening for p...	18 Years - 90 Years	Beth Israel Deaconess Medical Center
A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study)	NCT02034916	Breast Neoplasm... BRCA 1 Gene Mut... BRCA 2 Gene Mut...	talazoparib	18 Years -	Pfizer
A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study)	NCT02034916	Breast Neoplasm... BRCA 1 Gene Mut... BRCA 2 Gene Mut...	talazoparib	18 Years -	Pfizer

Spots Global Cancer Trial Database for brca 2

Every month we try and update this database with for brca 2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for brca 2

Every month we try and update this database with for brca 2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for brca 2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.