A Study of ZW191 in Participants With Solid Tumors

A Phase 1, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Ascending Doses of a Folate Receptor Alpha Antibody Drug Conjugate, ZW191, in Participants With Advanced Solid Tumors

The purpose of this study is to find out if ZW191 is safe and can treat participants with advanced cancers, including ovarian, endometrial, and non-small cell lung cancers.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ZW191

Detailed Description

Part 1 of the study will evaluate the safety and tolerability of ZW191. Part 2 of the study will further evaluate safety and explore the potential anti-tumor activity of ZW191.

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, WA 6009
    • Linear Clinical Research
  • St Leonards, Australia, NSW 2065
    • Royal North Shore Hospital Northern Sydney Cancer Centre
• Japan
  • Kashiwa-shi, Japan, 277-8577
    • National Cancer Center Hospital East
  • Saitama, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Centre Singapore
  • Singapore, Singapore, 119228
    • National University Health System (NUHS) - National University Cancer Institute Singapore (NCIS)
  • Singapore, Singapore, 217562
    • Curie Oncology
• South Korea
  • Goyang-si, South Korea, 10408
    • National Cancer Center
  • Seongnam-si, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 6273
    • Gangnam Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28223
    • Next Oncology Madrid
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46009
    • Fundacion Instituto Valenciano de Oncologia (IVO)
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Next Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically or cytologically confirmed diagnosis of cancers with evidence of locally advanced (unresectable), recurrent and/or metastatic disease.
• Measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Adequate cardiac function: Cardiac left ventricular function, as defined by left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram (ECHO) or multigated acquisition scan (MUGA).
• Other adequate organ function.

Exclusion Criteria:

• Known additional malignancy that is progressing or requires active treatment or may interfere with study endpoints.
• Has received prior Topoisomerase I inhibitor(TOPO1i) antibody drug conjugate treatment, regardless of washout period.
• Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease.
• Severe chronic or active infections (including known active SARS-CoV-2 infection) requiring systemic therapy, including antibacterial, antifungal, or antiviral therapy.

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: ZW191	Drug: ZW191; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 ZW191	Up to 3 weeks
Incidence of adverse events (AEs; Parts 1 and 2)	Number of participants who experienced AEs, adverse events of special interest (AESIs), or serious adverse events (SAEs)	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
Clinical benefit rate (Parts 1 and 2)	Number of participants who achieved a best response of CR, PR, non-CR/non-progressive disease (PD), or stable disease (SD) lasting at least 180 days per 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 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
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 SD during treatment per RECIST v1.1	Up to approximately 2 years
Progression-free survival (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
Best overall response (BOR; Part 2)		Up to approximately 2 years
Serum or plasma concentration and PK parameters of ZW191 (Parts 1 and 2)	Maximum serum concentration and trough concentration of ZW191	Up to approximately 2 years
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)	Number of participants who develop ADAs	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Zymeworks BC Inc.
• Investigators: Study Director: Maggie Weinstein, MD, PhD, MPH, Zymeworks BC Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 13, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ADC; Advanced or Metastatic Cancers; Folate alpha receptor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ZWI-ZW191-101; 2024-512299-37-00 (Ctis)

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