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

Phase 1

Recruiting

• Conditions: Mesothelin-expressing Advanced Cancers
• Interventions: Drug: ZW171

• Registration Number: NCT06523803
• Lead Sponsor: Zymeworks BC Inc.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-07-22
• Study First Submitted QC: 2024-07-22
• Study First Posted: 2024-07-26
• Study Start: 2024-09-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-06
• Primary Completion: 2027-11
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZW171	ZW171	-

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs; Parts 1 and 2)	Up to approximately 2 years	Number of participants who experienced AEs or serious adverse events (SAEs)
Incidence of neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS; Parts 1 and 2)	Up to approximately 2 years	Number of participants who experienced neurotoxicity, including ICANS
Incidence of clinical laboratory abnormalities (Parts 1 and 2)	Up to approximately 2 years	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
Incidence of cytokine release syndrome (CRS; Parts 1 and 2)	Up to approximately 2 years	Number of participants who experienced CRS
Incidence of dose-limiting toxicities (DLTs; Part 1)	Up to 3 weeks	Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW171
Confirmed objective response rate (Part 2)	Up to approximately 2 years	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

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS), including 1-year OS (Part 2)	Up to approximately 2 years	The time from the first dose of ZW171 until the date of death from any cause
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)	Up to approximately 7 months	Number of participants who develop ADAs
Duration of response (DOR; Part 2)	Up to approximately 2 years	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
Progression-free survival (PFS), including 1-year PFS (Part 2)	Up to approximately 2 years	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
Confirmed objective response rate (Part 1)	Up to approximately 2 years	Number of participants who achieved a best overall response of either confirmed CR or PR during treatment according to RECIST v1.1
Disease control rate (DCR; Part 2)	Up to approximately 2 years	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
Serum concentration of ZW171 (Parts 1 and 2)	Up to approximately 7 months	Maximum serum concentration and trough concentration of ZW171

Trial Locations

Locations (5)

University of Colorado Health Sciences Center; 🇺🇸 Aurora, Colorado, United States

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

University of Southern California - Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States