A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers

A Phase 1, Open-label, Multicenter Study of ZW171 in Participants With Advanced or Metastatic Ovarian Cancer, Non-small Cell Lung Cancer (NSCLC), and Other Mesothelin Expressing Cancers

This study is being done to find out if ZW171 is safe and can treat participants with advanced (locally advanced [inoperable] and/or metastatic) mesothelin-expressing cancers.

Study Overview

• Status: Terminated
• Conditions: Mesothelin-expressing Advanced Cancers
• Intervention / Treatment: Drug: ZW171

Detailed Description

Part 1 of the study will evaluate the safety and tolerability of ZW171. Part 2 of the study will evaluate the anti-tumor activity of ZW171 while continuing to evaluate the safety and tolerability.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Dresden
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Yonsei University Health System - Severance Hospital
  • Seoul, South Korea
    • The Catholic University of Korea, Seoul St. Marys Hospital
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas' NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust
  • Sutton, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
• United States
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California - Norris Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health Sciences Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • New York
    • New York, New York, United States, 10011
      • Icahn School of Medicine at Mount Sinai (ISMMS) - The Blavatnik Family-Chelsea Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically confirmed diagnosis of cancers with evidence of locally advanced (unresectable) and/or metastatic disease. Cancers that are refractory to all available standard of care (SOC) treatment, cancers for which no SOC treatment is available, or the participant cannot tolerate or refuses SOC therapy.
• An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Adequate cardiac left ventricular function, as defined by left ventricular ejection fraction ≥ 50% as determined by either echocardiogram or multigated acquisition scan.
• Adequate organ function.

Exclusion Criteria:

• Known additional malignancy that is progressing or that has required active treatment.
• Undergone prior allogenic tissue (e.g., hematopoietic stem cell) or solid organ transplantation within the last 5 years.
• Ongoing, clinically significant toxicity (Grade ≥ 2) associated with prior cancer therapies, with the exception of alopecia.
• Advanced/metastatic, symptomatic, visceral spread, at risk of life-threatening complications in the short-term (including participants with massive uncontrolled effusion [pleural, pericardial], pulmonary lymphangitis, active unresolved bowel obstruction, massive ascites [requiring paracentesis >2 times within 2 weeks prior to the first dose], and over 50% liver involvement).
• Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of participants with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment).
• Active or recurrent clinically significant autoimmune disease requiring systemic high-dose corticosteroids or immunosuppressive drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZW171	Drug: ZW171; Administered per protocol requirements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs; Part 1)	Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW171	Up to 3 weeks
Incidence of adverse events (AEs; Parts 1 and 2)	Number of participants who experienced AEs or serious adverse events (SAEs)	Up to approximately 2 years
Incidence of cytokine release syndrome (CRS; Parts 1 and 2)	Number of participants who experienced CRS	Up to approximately 2 years
Incidence of neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS; Parts 1 and 2)	Number of participants who experienced neurotoxicity, including ICANS	Up to approximately 2 years
Incidence of clinical laboratory abnormalities (Parts 1 and 2)	Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0	Up to approximately 2 years
Confirmed objective response rate (Part 2)	Number of participants who achieved a best overall response of either confirmed complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed objective response rate (Part 1)	Number of participants who achieved a best overall response of either confirmed CR or PR during treatment according to RECIST v1.1	Up to approximately 2 years
Duration of response (DOR; Part 2)	The time from the first objective response (CR or PR) to the first documented progressive disease (PD) per RECIST v1.1 or death within 30 days of last dose of study treatment from any cause. Only participants who achieve a confirmed response will be included in the analysis	Up to approximately 2 years
Progression-free survival (PFS), including 1-year PFS (Part 2)	The time from the first dose of study treatment to the date of first documented PD per RECIST v1.1 or death from any cause	Up to approximately 2 years
Disease control rate (DCR; Part 2)	Number of participants who achieved a best response of CR, PR, non-CR/non-PD (for participants who have only non-target lesions), or stable disease (SD) during treatment per RECIST v1.1	Up to approximately 2 years
Overall survival (OS), including 1-year OS (Part 2)	The time from the first dose of ZW171 until the date of death from any cause	Up to approximately 2 years
Serum concentration of ZW171 (Parts 1 and 2)	Maximum serum concentration and trough concentration of ZW171	Up to approximately 7 months
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)	Number of participants who develop ADAs	Up to approximately 7 months

Collaborators and Investigators

• Sponsor: Zymeworks BC Inc.
• Investigators: Study Director: Pranshul Chauhan, MSc, MB, BCh, BAO, Zymeworks BC Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): October 1, 2025

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: ADC; Antibody drug conjugate; Advanced or Metastatic Cancers
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ZWI-ZW171-101; 2024-511119-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No