Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

ZEN003694 will be administered PO QD with Talazoparib PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD as monotherapy at the RP2D in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 PO QD with Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

ZEN003694 will be administered PO QD with Talazoparib PO QD at the RP2D in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

ZEN003694

This is a two-part open label, non-randomized, Phase 2, study of ZEN003694 in combination with Talazoparib in patients with TNBC without germline mutations of BRCA1 or BRCA2. Part 1 is a dose escalation and Part 2 is a Simon 2-Stage design. There are 3 expansion cohorts: Expansion Cohort A (combination treatment in post-TROP2-ADC patients), Expansion Cohort B (ZEN003694 monotherapy), and Expansion Cohort C (combination treatment in TROP2-ADC-naive patients).

A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer

A Phase 2b Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer

Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably or definitely related to study drug.

CBR defined as a confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST v1.1

ORR defined as a confirmed complete response (CR) or partial response (PR) by RECIST 1.1

CBR defined as a confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST 1.1

Time from randomization to documented disease progression or death

For subjects with a confirmed response of PR or CR, duration of response is measured from the date of the first response until the time that overall disease progression (radiographic progressive disease or clinical deterioration) or death is documented.

Plasma concentrations of ZEN003694 and the active metabolite ZEN003791 will be measured.

Plasma concentrations of talazoparib will be measured.

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (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.

European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (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.

Pfizer

Newsoara Biopharma Co., Ltd.

Zenith Epigenetics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

ZEN003694 will be administered orally as a single agent once daily in 28-day cycles, enrolling mCRPC patients.

This is an open label, Phase 1, dose escalation and dose confirmation study of ZEN003694 in patients with mCRPC.

A Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase 1 Safety and Tolerability Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer

A DLT is a treatment-related, clinically significant adverse event or laboratory abnormality occurring during the first cycle of treatment (Day 1 thru Day 28).

AUC is defined as the area under the curve (plasma concentration of drug over time).

Cmax is defined as maximum or peak plasma concentration of drug.

Cmin is defined as minimum or trough plasma concentration of drug.

Tmax is defined as the time from dosing to the maximum plasma concentration.

t/12 is defined as the half-life of drug.

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Lung Neoplasms

Recurrence

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All patients enrolled on the study will undergo treatment with ZEN003694 60mg po qd on a 5 days on/2 days off schedule in an every 21-day cycle. All assessments, including drug dosing, have a window of +/- 7 days unless otherwise noted.

ZEN003694 60mg po qd on a 5 days on 2 days off schedule in an every 21-day cycle

Paul Paik, MD

Mark Kris, MD

The purpose of this study is to find out whether ZEN003694 is an effective treatment for people with advanced squamous cell lung cancer with a mutation in the NSD3 gene.

ZEN003694 is a type of drug called a BET inhibitor. Researchers think ZEN003694 may help here because the drug works by blocking a group of proteins called bromodomain and extra-terminal (BET) proteins, which may counteract the effect of NSD3 on tumor growth. Blocking these proteins may slow or stop the growth of the cancer.

This is a single-arm phase 2 study of ZEN003694 in patients with advanced NSD3- amplified squamous cell lung cancer.

A Study of ZEN003694 in People With Squamous Cell Lung Cancer

Phase 2 Trial of ZEN003694 in Squamous Cell Lung Cancer Patients Harboring NSD3 Amplification

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Response to ZEN003694 will be determined using the sum unidimensional measurements of the target lesions present on the scan. Unidimensional measurement rules will adhere to RECIST 1.1 guidelines.(6) Classification of response will be categorized by RECIST 1.1 (CR, PR, SD, PD).

Memorial Sloan Kettering Cancer Center

Patients who have completed participation in their original ZEN003694-002 protocol and have clinical benefit as determined by the investigator may continue to receive treatment with ZEN003694 in combination with enzalutamide

Enzalutamide

Continuation Protocol for ZEN003694 in Patients Experiencing Clinical Benefit While Enrolled in a ZEN003694 Protocol

This is an open label, non-randomized, single-arm continuation protocol study using ZEN003694. Patients who have completed participation in their original ("parent") ZEN003694 protocol and have clinical benefit as determined by the investigator may continue to receive treatment with ZEN003694 in the continuation protocol. The patient must have been enrolled in a Zenith Epigenetics sponsored ZEN003694 therapeutic study to be eligible for participation in this continuation protocol.

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to the initiation of the combination therapy (Lead-in) to reach steady state concentration (Css) prior to Cycle 1. After the Lead-in, ZEN003694 (72 mg) will be administered orally one daily in combination with daily enzalutamide for 28-day cycles.

Patients will be administered enzalutamide (160 mg) orally once daily for 21 days prior to Cycle 1 Day 1 (Lead-in). After the Lead-in, patients will be administered enzalutamide 160 mg orally once daily for 28-day cycles. Active control patients will have the option to cross-over to treatment with ZEN003694 in combination with enzalutamide upon confirmed radiographic progression by PCWG3 criteria by independent central review.

Zenith Study Team

This is an open-label, randomized, Phase 2b study of ZEN003694 in combination with enzalutamide vs. enzalutamide monotherapy in patients with mCRPC who have progressed on prior abiraterone by PCWG3 criteria. Disease must have progressed on only abiraterone by PCWG3 criteria prior to study entry.

The patient population will be separated into two cohorts:

Cohort A: Patients with poor response to prior abiraterone defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: \< 12 months duration on abiraterone or failure to achieve PSA nadir of 0.2 ng/mL while taking abiraterone, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: \< 6 months duration on abiraterone or failure to achieve PSA50 response while on abiraterone

Cohort B: Patients with response to prior abiraterone, defined as:

* Abiraterone started in hormone-sensitive prostate cancer (HSPC) disease setting: ≥ 12 months duration on abiraterone and nadir PSA \< 0.2 ng/mL, or;
* Abiraterone started in castrate-resistant prostate cancer (CRPC) disease setting: ≥ 6 months duration on abiraterone and confirmed PSA50 response

ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer

A Randomized Phase 2b Study of ZEN003694 in Combination With Enzalutamide Versus Enzalutamide Monotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer

Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3.

Time from date of randomization to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated by RECIST 1.1 and PCWG3

Time from date of randomization to the date of first disease radiographic progression, clinical progression, or death for any reason. Radiographic progression of disease will be evaluated by RECIST 1.1 and PCWG3 by investigator assessment. Clinical progression is significant pain increase or clinical deterioration that requires initiating another line of treatment.

Time from date of randomization to the date of death from any cause

PSA response is a reduction in serum PSA concentration of ≥50% from baseline.

Proportion of the patients who have either a complete response (CR) or partial response (PR) by RECIST 1.1 criteria who have measurable disease at baseline.

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 a 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.

EORTC QLQ-PR25: prostate cancer specific instrument with 25 questions used in conjunction with EORTC QLQ-C30 to assess the participant QoL. Used to evaluate 5 multi-item scales (urinary, bowel, and hormonal treatment-related symptoms, sexual activity, and sexual functioning) and one single item (problems due to incontinence aid use). Each question assessed on a 4-point scale (1= not at all, 2= a little, 3= quite a bit, 4= very much). Scores averaged, transformed to 0-100 scale; higher score=better quality of life/better level of functioning.

Time from date of randomization to the first dose of chemotherapy.

Time from date of randomization to the first SRE such as pathological fracture, surgery/radiotherapy for pain/prevention of fracture, hypercalcemia, and spinal cord compression.

Astellas Pharma Inc

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

ZEN003694: 48.0 mg daily (oral) in 28-day cycles

Talazoparib: 0.75 mg daily (oral) at the same time as ZEN003694

ZEN003694 has shown promising activity in the treatment of solid tumors and hematologic (blood) cancers by reducing the multiplication of cancer cells.

Talazoparib kills cancer cells by inhibiting and trapping the enzyme PARP, which is known to be involved in the development of many types of cancers.

Josh Plasmeyer

Haider Mahdi, MD

Josh Plassmeyer, MS

Clare Berger, RN, BSN

This Phase 2, open label, study with safety lead in of oral talazoparib in combination with ZEN003694 given daily in 28-day cycles will enroll patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma.

This study aims to determine how effective the combination of ZEN003694 and talazoparib is based on how patients respond. ZEN003694 (and developed by Zenith Epigenetics Ltd.) has shown promising activity in the treatment of solid tumors and hematologic (blood) cancers by reducing the multiplication of cancer cells. Talazoparib is an extremely effective drug being developed for the treatment of a variety of human cancers. Talazoparib kills cancer cells by inhibiting and trapping the enzyme PARP, which is known to be involved in the development of many types of cancers. These two drugs are not FDA approved in the treatment of ovarian cancer.

ZEN003694 Combined With Talazoparib in Patients With Recurrent Ovarian Cancer

Phase ll Study of a BET Inhibitor, ZEN003694, Combined With a PARP Inhibitor, Talazoparib, in Patients With Recurrent Ovarian Cancer

Confirmed complete response or partial response by RECIST 1.1. Per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Adverse Events which occur from first day of treatment, characterized by type, grade and relatedness to treatment according to CTCAE v5.0, considered to be possibly, probably or definitely related to study treatment.

Time from start of response to documented disease progression by RECIST v1.1 or death due to any cause. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:

Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Time from first response to to treatment until documented disease progression by RECIST v1.1 or death due to any cause. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:

Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Overall survival (OS), defined as time from first dose of study treatment until death due to any cause.

Haider Mahdi

Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Disease Attributes

Niraparib

ZEN003694: Oral capsules - Starting dose 36 mg Dose escalated to 48 mg, following the mTPI-2/Keyboard design administered orally once daily in 28-day cycles

Niraparib: Oral tablets - Starting dose 100 mg Dose escalated to 200 mg, following the mTPI-2/Keyboard design administered once daily at the same time as ZEN003694

A bromodomain extra-terminal inhibitor (BETi) that blocks a group of proteins called bromodomain and extra-terminal (BET), which may counteract the effect of NSD3 on tumor growth.

An anti-cancer medication (PARP inhibitor) used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer .

Kelsey Mitch, RN

Joshua Plassmeyer, MS

Haider S Mahdi, MD

This Phase I, open label, dose determining study of oral niraparib in combination with ZEN003694 given daily in 28-day cycles will enroll patients with metastatic or recurrent solid cancer. Dose escalation will follow the mTPI-2/Keyboard design. Eligible patients will receive therapy until disease progression or unacceptable toxicities are experienced.

PARPis impair the repair of single strand DNA breaks leading to double strand DNA breaks especially in patients with defects in the HR pathway. PARP is have been extensively studied in ovarian cancer and are approved for patients with germline or somatic BRCA mutant ovarian cancer after 2-3 lines of chemotherapy. PARPis have been also approved as maintenance therapy in first line and recurrent ovarian cancer after partial or complete response to platinum-based therapy. PARPis have prominent activity in BRCA mutated cancer with lower activity in the BRCA wild type HRD negative ovarian cancer. Approximately 18-24% of ovarian cancer harbor somatic or germline BRCA mutation and 50% harbor alteration in the homologous recombination (HR) pathway.

Further, PARPi therapy is frequently associated with PARPi resistance. Therefore, there is a need to reverse PARPi resistance and enhance response to PARPi in PARPi resistant ovarian cancer. Recently, significant pre-clinical evidence has shown that BETi's synergize with PARPi's through downregulation of the transcription of several HR genes. It is hypothesized that BETi may suppress HR and enhance non-homologous end joining thereby sensitizing HR-proficient cancer cells to PARP inhibition, and also BETi has been described to reverse PARPi resistance. To test this hypothesis, this Phase I trial will test the combination of niraparib and ZEN003694 in recurrent or metastatic solid cancers.

ZEN003694 Combined With Niraparib in Patients With Metastatic or Recurrent Solid Tumors

Phase l Study of a BET Inhibitor, ZEN003694, Combined With a PARP Inhibitor, Niraparib in Patients With Metastatic or Recurrent Solid Tumors

Frequency and severity of adverse events (AE) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. The maximum grade for each toxicity type will be recorded for each patient.

Frequency of dose-limiting toxicities (DLTs) (AEs leading to discontinuation of treatment).

The mTPI-2/Keyboard design is a Bayesian interval dose determining design. The target toxicity rate for the MTD for this combination therapy is defined at 0.30 with an acceptable toxicity probability interval (0.25, 0.35). The MTD is selected based on the dose estimate closest to the target toxicity rate, and the recommend phase II dose will be determined based on the MTD and all available safety and PK data.

Maximum observed concentration (Cmax) in blood taken from patients treated with ZEN003694 combined with niraparib.

Area under the serum concentration-time curve (AUC) in blood taken from patients treated with ZEN003694 combined with niraparib.

Proportion of participants achieving a best response of CR or PR per RECIST v1.1, at each dose level. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time from start of treatment to disease progression or death in patients who achieve Complete Response (CR) or Partial Response (PR) (whichever is recorded first) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Median number of months from start of treatment to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (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). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Median length of time from start of treatment that patients remain alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer	NCT03901469	Triple Negative...	ZEN003694 Talazoparib	18 Years -	Zenith Epigenetics
A Study of ZEN003694 in Patients With Metastatic Castration-Resistant Prostate Cancer	NCT02705469	Metastatic Cast...	ZEN003694	18 Years -	Zenith Epigenetics
A Study of ZEN003694 in People With Squamous Cell Lung Cancer	NCT05607108	Squamous Cell L...	ZEN003694	18 Years -	Memorial Sloan Kettering Cancer Center
Continuation Protocol for ZEN003694 in Patients Experiencing Clinical Benefit While Enrolled in a ZEN003694 Protocol	NCT04145375	mCRPC	ZEN003694 Enzalutamide	18 Years -	Zenith Epigenetics
ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer	NCT04986423	Metastatic Cast...	ZEN003694 Enzalutamide	18 Years -	Zenith Epigenetics
ZEN003694 Combined With Talazoparib in Patients With Recurrent Ovarian Cancer	NCT05071937	Ovarian Cancer Peritoneal Canc... Fallopian Tube ...	ZEN003694 Talazoparib	18 Years -	University of Pittsburgh
ZEN003694 Combined With Niraparib in Patients With Metastatic or Recurrent Solid Tumors	NCT06161493	Ovarian Cancer Recurrent Solid...	ZEN003694 Niraparib	18 Years -	University of Pittsburgh
A Study of ZEN003694 and Talazoparib in Patients With Triple Negative Breast Cancer	NCT03901469	Triple Negative...	ZEN003694 Talazoparib	18 Years -	Zenith Epigenetics
ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer	NCT04986423	Metastatic Cast...	ZEN003694 Enzalutamide	18 Years -	Zenith Epigenetics

Spots Global Cancer Trial Database for zen003694

Every month we try and update this database with for zen003694 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 zen003694

Every month we try and update this database with for zen003694 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 zen003694 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.