Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Central Nervous System Depressants

Pembrolizumab

Carboplatin

Antibodies

Antibodies, Monoclonal

Hormones

Nitrous Oxide

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will be enrolled in a standard 3+3 dose-escalation scheme to establish a Maximum Tolerated dose (MTD) of Azenosertib, starting at Dose Level 0, de-escalating to Dose Level -1, and escalating to Dose Levels 1 and 2.

* Baseline visit with CT or MRI scan.
* CT or MRI scan every 9 weeks until 27 weeks then every 12 weeks.
* Cycle 1 through End of Treatment:

  * Days 1 through 5, 8 through 12, and 15 through 19 of 21 Day Cycle: Predetermined dose of Azenosertib 1 x daily.
  * Day 1 of 21 Day Cycle: Predetermined dose of Pembrolizumab 1x daily.
  * Days 1 and 8 of 21 Day Cycle: Predetermined dose of Carboplatin 1x daily.
* End of Treatment visit
* Follow up: every 6 months
* Dose de-escalation and escalation will follow dose-limiting toxicities specifications (DLTs) per the protocol. The MTD is the highest dose level with ≤1 DLT in a cohort of 6 participants and the study will proceed to Phase 2.

Participants will complete:

* Baseline visit with CT or MRI scan and tumor biopsy.
* CT or MRI scan every 9 weeks until 27 weeks then every 12 weeks.
* Cycle 1 through End of Treatment:

  * Days 1 through 5, 8 through 12, and 15 through 19 of 21 Day Cycle: Predetermined dose of Azenosertib 1x daily.
  * Day 1 of 21 Day Cycle: Predetermined dose of Pembrolizumab 1x daily.
  * Days 1 and 8 of 21 Day Cycle: Predetermined dose of Carboplatin 1x daily.
* Tumor biopsy during Cycle 2.
* End of Treatment visit
* Follow up: every 6 months

WEE1 inhibitor, 25 or 100 mg tablet, taken orally per protocol.

Azenosertib

Platinum coordination compound, 5-, 15-, 45-, and 60-mL vials, via intravenous (into the vein) infusion per institutional standards.

Humanized immunoglobulin G4 monoclonal antibody, 4-mL vials, via intravenous (into the vein) infusion per protocol.

Filipa Lynce, MD

This research is being done to evaluate the safety and effectiveness of a drug currently known as Azenosertib (ZN-C3) in combination with the drugs carboplatin and pembrolizumab in metastatic triple-negative breast cancer.

The names of the study drugs involved in this study are:

* Azenosertib (a type of WEE1 inhibitor)
* Carboplatin (a type of platinum compound)
* Pembrolizumab (a type of monoclonal antibody)

This is a non-randomized, open-label, phase I/II study designed to evaluate the safety and efficacy of azenosertib in combination with carboplatin and pembrolizumab in participants with metastatic triple negative breast cancer (TNBC) Azenosertib is a medication that targets WEE1, an important protein in tumor growth.

The U.S. Food and Drug Administration (FDA) has not approved azenosertib as a treatment for metastatic triple-negative breast cancer.

The FDA has approved carboplatin as a treatment option for metastatic triple-negative breast cancer and it is considered standard of care for breast cancer.

The FDA has approved pembrolizumab for metastatic triple-negative breast cancer, but it is currently approved only for PD-L1 positive cancer.

The research study procedures include screening for eligibility, study treatment visits, blood tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, electrocardiograms (EKGs), and tumor biopsies in Phase 2.

It is expected that about 12-18 people will take part in the phase 1 portion and 60 people for the phase 2 portion of this research study.

Zentalis Pharmaceuticals is funding this research study and providing Azenosertib. Merck is supporting this research study by providing pembrolizumab.

A Phase I/II Single-arm Trial of Azenosertib (ZN-c3) Combined With Carboplatin and Pembrolizumab in Patients With Metastatic Triple-negative Breast Cancer (ZAP-IT)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Detailed DLT consideration outline in protocol section 5.4. Toxicities are to be assess according to the CTCAE v5. Management and dose modifications associated with the above adverse events outlined in protocol section 6.

The MTD is defined as the highest dose level with ≤1 DLT in a cohort of 6 participants. See previous primary outcome measure for the DLT definition. If 0 out of 3 participants experience DLT, next dose level will be proceeded. If \>=1 out of the group suffer DLT, dose escalation will be stopped and 3 additional participants will be entered at the next lowest dose level. If \<=1 out of 6 DLTs, this dose level is considered as MTD.

ORR was defined as the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. 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.

CBR is defined as the number of participants who achieved complete response (CR), partial response (PR), and stable disease (SD) lasting more than 24 weeks based on RECIST 1.1 criteria.

PFS based on Kaplan-Meier methodology is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

OS is Overall survival based on the Kaplan-Meier method is defined as the time from registration to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

DOR based on Kaplan-Meier methodology is defined as the time from date of first documented confirmed objective response to date of first documented progressive disease (PD). Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

The percentage of participants who experienced a maximum grade 3-5 treatment-related adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.

Merck Sharp & Dohme LLC

Zentalis Pharmaceuticals

Sponsor Investigator

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Olaparib

Onvansertib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Patients receive olaparib PO BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery.

Patients receive cobimetinib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery.

Patients receive onvansertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Patients receive azenosertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Cobimetinib

Charles D. Lopez

Charles D Lopez

This early phase I trial aims to determine how cobimetinib, olaparib, LY3214996, or onvansertib works in patients with pancreatic cancer. Validation of cobimetinib, or olaparib, LY3214996, and onvansertib molecular targets will be explored by comparing pre-treatment biopsies with post-treatment specimens. This knowledge will help design future biomarker driven trials to determine whether giving cobimetinib, or olaparib, LY3214996, or onvansertib will work better than standard treatments in patients with pancreatic cancer.

PRIMARY OBJECTIVE:

I. Independently assess the pharmacodynamic (PD) feasibility of detecting a measurable change in tumor biology at post-treatment from baseline (i.e., before the study treatment window) for all feasibility-evaluable participants in each study arm.

SECONDARY OBJECTIVES:

I. Assess preliminary safety and tolerability of the proposed study agent(s) in each study arm.

EXPLORATORY OBJECTIVES:

I. Identify predictive biomarkers of sensitivity to assigned study agent(s).

II. Identify emerging mechanism(s) of resistance to assigned study agent(s).

III. Determine cellular and molecular changes in pancreatic tumor cells exposed to assigned study agent(s).

IV. Identify tumor markers suggestive of combinatorial therapy that could overcome resistance to therapy.

OUTLINE: Patients are assigned to 1 of 4 arms.

ARM I: Patients receive olaparib PO twice daily (BID) on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

ARM II: Patients receive cobimetinib orally (PO) once daily (QD) on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

ARM IV: Patients receive onvansertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

ARM V: Patients receive azenosertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

After completion of study treatment, patients are followed up for 30 days.

Targeted Pathway Inhibition in Patients With Pancreatic Cancer

A Window of Opportunity Strategy for Targeted Pathway Inhibition in Patients With Pancreatic Ductal Adenocarcinoma

Will be estimated with a 95% confidence interval (CI).

Assessed per Common Terminology Criteria for Adverse Events version 5.0. The 95% CI will be reported with the point estimate of toxicity rate. All grade 3+ acute toxicities will also be summarized with its grade.

American Association for Cancer Research

Oregon Health and Science University

Genentech, Inc.

Cardiff Oncology

OHSU Knight Cancer Institute

Principal Investigator

Stomach Neoplasms

Esophageal Neoplasms

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

Trastuzumab

Trastuzumab deruxtecan

Camptothecin

Immunoconjugates

Immunologic Factors

Topoisomerase I Inhibitors

Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 1-5, 8-12, and 15-19 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial.

Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 8-12 and 15-19 of cycle 1 and days 1-5, 8-12, and 15-19 in subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study.

Patients receive treatment as in the dose escalation arm. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study.

Biopsy

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Multigated Acquisition Scan

Trastuzumab Deruxtecan

Funda Meric-Bernstam

This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive and cyclin E amplified gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.

PRIMARY OBJECTIVE:

I. To evaluate the safety and tolerability of trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with azenosertib (ZN-c3) in human epidermal growth factor receptor 2 (HER2)-expressing/amplified solid tumors.

SECONDARY OBJECTIVES:

I. To observe and record the antitumor activity of the T-DXd (DS-8201a) and azenosertib (ZN-c3) combination.

II. To assess the pharmacodynamic effects of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3).

III. To assess predictors of response and acquired resistance to the T-DXd (DS-8201a) and azenosertib (ZN-c3) combination.

OUTLINE: This is a dose-escalation study of azenosertib followed by a dose-expansion study.

DOSE ESCALATION: Patients receive T-DXd intravenously (IV) over 30-90 minutes on day 1 of each cycle and azenosertib orally (PO) once daily (QD) on days 1-5, 8-12, and 15-19 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and collection of blood samples at screening and on study and undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

DOSE EXPANSION: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 8-12 and 15-19 of cycle 1 and days 1-5, 8-12, and 15-19 in subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study.

COHORT 2: Patients receive treatment as in the dose escalation arm. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months in years 1 and 2 and every 6 months in year 3.

Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors

Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing/Amplified Cyclin E-Amplified Gastric/Gastroesophageal Junction Cancer and Other Solid Tumors With HER2 Expression

"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

A Bayesian optimal interval design will be used to determine the maximum tolerated dose of the T-DXd (DS-8201a) and azenosertib (ZN-c3) combination.

DLTs will be defined as the below based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

The incidence of AEs of the T-DXd (DS-8201a) and azenosertib (ZN-c3) combination, including but not limited to treatment-emergent adverse events, serious adverse events, deaths, and clinical laboratory abnormalities, will be assessed by the NCI CTCAE version 5.0. AEs will be tabulated by grade and by relationship to the study drugs. The proportion of patients who discontinue study treatment due to AEs and the unacceptable toxicity rate will be estimated with a 95% confidence intervals (CIs).

ORR will be the percentage of patients with complete response (CR) or partial response (PR), as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR will be estimated with a 95% CIs.

Disease progression will be assessed by RECIST version 1.1. PFS will be estimated using the product-limit estimator of Kaplan-Meier.

Duration of response will be estimated using the product-limit estimator of Kaplan-Meier.

Two-sample t-test (or Wilcoxon rank sum test) or Chi-square test will be used to compare pharmacodynamic markers between the two expansion cohorts.

Predictors of response and acquired resistance may include baseline HER2 expression and copy number, cycle E amplification and expression and other genomic co-alterations, and transcriptional and proteomic profile. Logistic regression and Cox proportional hazards model will be used to assess the relationship between clinical responses and molecular and genomic biomarkers.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II Single-arm Trial of Azenosertib (ZN-c3) Combined With Carboplatin and Pembrolizumab in Patients With Metastatic Triple-negative Breast Cancer (ZAP-IT)	NCT06351332	Breast Cancer Breast Cancer F... Triple Negative... Hormone Recepto... HER2-negative B...	Azenosertib Carboplatin Pembrolizumab	18 Years -	Dana-Farber Cancer Institute
Targeted Pathway Inhibition in Patients With Pancreatic Cancer	NCT04005690	Locally Advance... Metastatic Panc... Stage II Pancre... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Cobimetinib Olaparib Onvansertib Azenosertib	18 Years -	OHSU Knight Cancer Institute
Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors	NCT06364410	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Locally Advance... Metastatic Gast... Metastatic Gast... Metastatic Mali... Unresectable Ga... Unresectable Ga... Unresectable Ma...	Azenosertib Biopsy Biospecimen Col... Computed Tomogr... Echocardiograph... Magnetic Resona... Multigated Acqu... Trastuzumab Der...	18 Years -	National Cancer Institute (NCI)
Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors	NCT06364410	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Locally Advance... Metastatic Gast... Metastatic Gast... Metastatic Mali... Unresectable Ga... Unresectable Ga... Unresectable Ma...	Azenosertib Biopsy Biospecimen Col... Computed Tomogr... Echocardiograph... Magnetic Resona... Multigated Acqu... Trastuzumab Der...	18 Years -	National Cancer Institute (NCI)
Targeted Pathway Inhibition in Patients With Pancreatic Cancer	NCT04005690	Locally Advance... Metastatic Panc... Stage II Pancre... Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Cobimetinib Olaparib Onvansertib Azenosertib	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for azenosertib

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

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