Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Talazoparib 1 mg/day for 24 cycles (28 days per cycle), continuing until withdrawn or discontinued, eg, until RECIST 1.1 progression or unacceptable toxicity.

Talazoparib1 mg/day is to be administered orally on a continuous dosing schedule.

Talazoparib Tosylate

Nuzhat Shaikh

Melinda Telli, MD

Melinda Telli

This purpose of this study is to test if talazoparib is safe and evaluate its response to advanced breast cancer associated with mutation of gene called PALB.

Primary Objectives: To evaluate whether talazoparib monotherapy can induce a 30% rate of objective response in subjects with advanced breast cancer associated with a PALB2 mutation.

Secondary Objective(s)

1. To evaluate the safety of talazoparib in subjects with advanced PALB2 mutation associated breast cancer
2. To evaluate the progression free survival (PFS) of talazoparib monotherapy in subjects with advanced PALB2 mutation associated breast cancer
3. To evaluate the clinical benefit rate (CBR) of talazoparib monotherapy in subjects with advanced PALB2 mutation associated breast cancer
4. To evaluate the ability of circulating tumor DNA (ctDNA) to identify and characterize the nature of PALB2 mutations at baseline and upon progression in subjects with advanced PALB2 mutation associated breast cancer treated with talazoparib monotherapy
5. To evaluate patient reported quality of life on talazoparib monotherapy

Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer

A Phase 2 Clinical Trial of Talazoparib Monotherapy for PALB2 Mutation Associated Advanced Breast Cancer

Response to treatment will be assessed as the number and proportion of participants who achieve either a confirmed complete response (CR) or partial response (PR). The outcome is reported as numbers without dispersion. Clinical response will be assessed as follows.

CR: Complete disappearance of all clinical evidence of disease PR: Decrease in size or amount of measurable disease lesions Progressive disease (PD): Worsening of lesions; appearance of new lesions; or recurrence of lesions Stable disease (SD): Disease status that is neither CR, PR, nor PD.

Clinical benefit rate (CBR) will be reported as the number and proportion of participants who achieve CR, PR or Stable Disease (SD) 6 months. The outcome is reported as numbers without dispersion.

Median progression free survival (PFS) will be assessed as the period of survival from therapy initiation without the development of progressive disease per RECIST 1.1. The outcome is reported as a number without dispersion.

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) EORTC QLQ C30 has 30 questions. First 28 questions evaluate 5 functional scales and 3 symptom scales and other single items. 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 evaluate global health status (GHS)/QoL. Each question is assessed on 7 point scale (1=very poor to 7=excellent). Scores averaged, transformed to 0-100 scale; higher score means a better quality of life/better level of functioning. The outcome will be reported as the median QoL score with standard deviation.

Toxicity will be assessed as adverse events that are severe or greater (≥ Grade 3), and possibly, probably, or definitely related to talazoparib. The outcome will be reported as the total number of qualifying events, a number without dispersion.

Pfizer

Stanford University

Blood and Lymph Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Anemia

Fanconi Syndrome

Fanconi Anemia

Congenital Aplastic Anemia

Prexasertib

Protein Kinase Inhibitors

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Geoffrey Shapiro, MD, PhD

This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.

This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:

1. Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
2. An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
3. A CCNE1 amplification

A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency

A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency

Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.

All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Dana-Farber Cancer Institute

Geoffrey Shapiro M.D., PhD

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Homologous Repair (HR) Deficiency Cohort

Replicative Stress Cohort

CCNE1 Amplification Cohort

Total

Age, Continuous

Sex: Female, Male

Non-Hispanic

Hispanic

Race/Ethnicity, Customized

United States

Region of Enrollment

Geoffrey Shapiro M.D., PhDDana-Farber Cancer Institute

>= 4 months

< 4 months

Progression-Free Rate at 4 Month

Incidence of Grade 4 Treatment-Related Toxicity

Objective Response Rate

Median Overall Survival (OS)

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Esophageal Neoplasms

Pancreatic Neoplasms

Melanoma

Head and Neck Neoplasms

Neoplasm Metastasis

Lung Neoplasms

Colonic Neoplasms

Endometrial Neoplasms

Urologic Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Esophageal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplastic Processes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Male Urogenital Diseases

Urologic Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Esophageal Cancer

Pancreatic Cancer

Neuroendocrine Tumor

Neuroepithelioma

Herbal and Botanical

Niraparib

Cola

Eligible participants will receive daily dosing of Niraparib.

Anjali Avadhani, MD

The purpose of this study is to further evaluate the efficacy and safety of niraparib in patients with locally advanced or metastatic solid tumors and a pathogenic or likely pathogenic tumor PALB2 (tPALB2) mutation.

Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors

A Single-Arm Phase-II Study of Niraparib in Locally Advanced or Metastatic Solid Tumor Patients With PALB2 Mutations

To evaluate overall response rate (ORR) as assessed by Independent Central Review (ICR) using RECIST v1.1

To evaluate duration of response (DOR) as assessed by ICR using RECIST v1.1

To evaluate progression-free survival (PFS) as assessed by ICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

To evaluate ORR as assessed by Investigator using RECIST v1.1

To evaluate DOR as assessed by Investigator using RECIST v1.1

To evaluate PFS as assessed by Investigator using RECIST v1.1

To evaluate Clinical Benefit Rate (CBR) as assessed by ICR and Investigator

To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by Investigator using RECIST v1.1

To evaluate intracranial ORR in participants with untreated measurable CNS lesions as assessed by ICR using RECIST v1.1

To evaluate safety and tolerability per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer	NCT04756765	Breast Cancer Advanced Breast...	Talazoparib Tos...	18 Years -	Stanford University
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency	NCT02873975	Advanced Cancer...	LY2606368	18 Years -	Dana-Farber Cancer Institute
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors	NCT05169437	Solid Tumor Breast Tumor Colon Tumor, Ma... Lung Tumor Urologic Cancer Pancreatic Canc... Melanoma Metastatic Canc... Locally Advance... Esophageal Canc... Endometrial Can... Head and Neck C...	Niraparib	18 Years -	Tempus AI
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors	NCT05169437	Solid Tumor Breast Tumor Colon Tumor, Ma... Lung Tumor Urologic Cancer Pancreatic Canc... Melanoma Metastatic Canc... Locally Advance... Esophageal Canc... Endometrial Can... Head and Neck C...	Niraparib	18 Years -	Tempus AI

Spots Global Cancer Trial Database for palb2 mutation