Clinical trial NCT06523803: A Study of ZW171 in Participants With Advanced or Metastatic Mesothelin-expressing Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mesothelin-expressing Advanced Cancers
Keywords: Advanced or Metastatic Cancers
ADC
Antibody drug conjugate
Lead sponsor: Zymeworks BC Inc.
Sponsor class: INDUSTRY
First posted: 2024-07-26
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs; Part 1)
timeFrame: Up to 3 weeks
measure: Incidence of adverse events (AEs; Parts 1 and 2)
timeFrame: Up to approximately 2 years
measure: Incidence of cytokine release syndrome (CRS; Parts 1 and 2)
timeFrame: Up to approximately 2 years
measure: Incidence of neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS; Parts 1 and 2)
timeFrame: Up to approximately 2 years
measure: Incidence of clinical laboratory abnormalities (Parts 1 and 2)
timeFrame: Up to approximately 2 years
measure: Confirmed objective response rate (Part 2)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Confirmed objective response rate (Part 1)
timeFrame: Up to approximately 2 years
measure: Duration of response (DOR; Part 2)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS), including 1-year PFS (Part 2)
timeFrame: Up to approximately 2 years
measure: Disease control rate (DCR; Part 2)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS), including 1-year OS (Part 2)
timeFrame: Up to approximately 2 years
measure: Serum concentration of ZW171 (Parts 1 and 2)
timeFrame: Up to approximately 7 months
measure: Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)
timeFrame: Up to approximately 7 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California - Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (ISMMS) - The Blavatnik Family-Chelsea Medical Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Zymeworks BC Inc.
name: Pranshul Chauhan, MSc, MB, BCh, BAO
role: STUDY_DIRECTOR
References: