ZN-c3 + Gemcitabine in Pancreatic Cancer

NCT06015659 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-336
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to test the safety and effectiveness of combining ZN-c3 and Gemcitabine in participants with pancreatic cancer. The names of the study drugs involved in this study are:

• ZN-c3 (a small molecule inhibitor of the WEE1 tyrosine kinase)
• Gemcitabine (a nucleoside metabolic inhibitor)

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma; Advanced Pancreatic Adenocarcinoma

Keywords

Advanced Pancreatic Adenocarcinoma; Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 6-month Progression-Free Survival (PFS) Rate

  6-month PFS rate is the proportion of participants remaining alive and progression free at 6 months. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

  18 months

Secondary Outcomes (4)

• Median Overall Survival (OS)

  18 months

• Median Progression-Free Survival (PFS)

  18 months

• Objective Response Rate (ORR)

  18 months

• Grade 3-5 Treatment-related Toxicity Rate

  18 months

Study Arms (1)

ZN-c3 + Gemcitabine

EXPERIMENTAL

Study procedures will be conducted as follows: * Cycle 1 - End of Treatment * Days 1 - 5 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Days 8 - 12 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Days 15 - 19 of 21-day cycle: Predetermined dose of ZN-c3 1x daily. * Day 1 and 8 of 21-day cycle: Predetermined dose of Gemcitabine 1x daily. * On-treatment tumor biopsy will be collected on either Cycle 1 Day 9 - 10 or Cycle 2 Day 9 - 10. * Tumor assessment by Computerized Tomography (CT) or Magnetic Resonance Imaging scan every 8 weeks while on treatment. * End of treatment visit with tumor assessment by CT or MRI and optional tumor biopsy. * Follow up visit every 2 months after treatment has ended.

Drug: Zentalis; Drug: Gemzar

Interventions

Zentalis DRUG

Small molecule inhibitor of the WEE1 tyrosine kinase, tablet taken orally per protocol.

Also known as: Zn-c3, KP-2638, azenosertib, C29H34N8O2.

ZN-c3 + Gemcitabine

Gemzar DRUG

Nucleoside metabolic inhibitor, per standard care via intravenous infusion.

Also known as: Gemcitabine hydrochloride, FF 10832, LY188011, C9H11F2N3O4 - HCl

ZN-c3 + Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a pathologically confirmed advanced pancreatic adenocarcinoma that is not curable with standard approaches based on the judgement of the treating investigator. Patients with metastatic pancreatic cancer and unresectable pancreatic cancer are eligible.
• Patients must have progressed or not tolerated a platinum-based regimen prior to enrolling on the trial.
• Patients must have received no more than 1 prior lines of platinum-based chemotherapy in the metastatic setting. Therapy given in the adjuvant or neoadjuvant setting is counted as a prior therapy if it occurred less than 6 months before cancer recurrence or progression.
• Age ≥ 18 years. As no dosing or adverse event data are currently available in participants \< 18 years of age, children and adolescents are excluded from this study.
• ECOG performance status of 0 or 1 (see Appendix A) with no deterioration over the previous 2 weeks prior to day of first dosing (Cycle 1, Day 1).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3 excluding measurements obtained within 3 days after transfusion of platelets
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with documented Gilbert's Syndrome.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Albumin ≤2.5 x institutional ULN; ≤ 5 × institutional ULN if liver metastases ≥ 2.7 g/dL
• Creatinine clearance (CrCl) ≥ 50 ml/min based on Cockroft-Gault method
• Participants must have measurable disease by RECIST v. 1.1 criteria and be willing to undergo a pre-treatment and on-treatment tumor biopsy. The biopsy requirement can be waived only with approval from the sponsor-investigator.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated, unless there is a drug-drug interaction with study medication.
• Patient has read and understands the informed consent form (ICF) and has been given written ICF prior to any study procedures which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

You may not qualify if:

• Patients who have previously received a WEE1 inhibitor are not eligible.
• Patients who received gemcitabine for incurable pancreatic cancer (locally advanced unresectable or metastatic) or patients progressing within 6 months of receiving neoadjuvant/adjuvant gemcitabine.
• Use of an anti-cancer treatment drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to the first dose of ZN-c3.
• Active use of treatment prescription or non-prescription drugs, or food and herbal supplements, that are strong/moderate CYP3A4 inhibitors, P-gp inhibitors, or strong CYP3A4 inducers.
• Any prior palliative radiation to ≥5% of the bone marrow, and must have been completed and recovered from adverse effects of therapy at least 21 days prior to the first dose of ZN-c3.
• Participants who have undergone major surgical procedures ≤ 28 days, or minor surgical procedures ≤ 7 days, of the first dose of ZN-c3. No waiting period is required following port-a-cath or other central venous access placement.
• Presence of CTCAE v5.0 Grade \>1 toxicity from prior therapy (except alopecia, anorexia or CTCAE grade 2 peripheral neuropathy).
• Patient is unable to swallow oral medications. Note: Patient may not have a percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral nutrition (TPN).
• Participants with known malignant central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or hemorrhage for at least 2 weeks after the completion of treatment (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrollment.
• History of hypersensitivity to compounds of similar chemical or biologic composition to gemcitabine or ZN-c3.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection\*, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or psychiatric illness/social situations that would limit compliance with study requirements.
• Recurrent, active or suspected infection and/or patients who are predisposed to an increased risk of severe infection. Patients with infections that require antibiotics or antifungal agents may be eligible, provided that infection is resolved and treatment is completed at least 7 days prior to study treatment start.
• Participants with a clinically significant gastrointestinal disorder that in the opinion of the treating investigator could impact the absorption of the study drugs, including but not limited to refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of ZN-c3.
• Participants with a history of a clinically relevant second primary malignancy within the past 2 years. Exceptions include: resected basal and squamous cell carcinomas of the skin and completely resected carcinoma in situ of any type.
• Administration of strong or moderate CYP3A4 inhibitors or inducers and P-gp inhibitors. (See Appendix B)

Sponsors & Collaborators

• Brandon Huffman, MD: lead
• Lustgarten Foundation: collaborator
• K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc: collaborator
• Stand Up To Cancer: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Brandon Huffman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: August 29, 2023
• Study Start: November 16, 2023
• Primary Completion: August 6, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)