Trial of ZW25 in Patients With Advanced HER2-expressing Cancers

Official Title

Phase I Trial of ZW25 in Patients With Locally Advanced (Unresectable) and/or Metastatic HER2-expressing Cancers

Summary:

To evaluate the maximal tolerated dose (MTD), optimal biological dose (OBD) or other recommended dose (RD), and overall safety and tolerability of ZW25 in patients with locally advanced (unresectable) and/or metastatic HER2-expressing cancers.

Trial Description

Primary Outcome:

• The proportion of patients experiencing dose limiting toxicities
• The proportion patients who experience laboratory abnormalities and/or adverse events as defined by CTCAE v4.03 that are related to treatment

Secondary Outcome:

• Serum concentrations of ZW25
• The proportion of patients who develop detectable anti-drug antibodies
• The proportion of patients with an objective response (partial response or complete response) as defined by RECIST 1.1 criteria
• Progression free survival as defined by RECIST 1.1 criteria

Part 1, Dose Escalation: Patients with any HER2-expressing cancer that is either HER2 1+, 2+ or 3+ by immunohistochemistry (IHC) and has progressed after all standard of care therapies will receive escalating doses of ZW25 in order to identify either the highest dose of study drug possible that will not cause unacceptable side effects or the dose of study drug which is thought to be associated with optimal biologic activity. Part 2, Dose Expansion: Patients will be enrolled into one of the below cohorts based the level of HER2 expression and cancer type.

• Cohort 1: HER2 IHC 2+/FISH negative breast cancer

• Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH positive breast cancer

• Cohort 3: HER2 IHC 2+/FISH negative gastric/ GEJ cancer

• Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH positive gastric/GEJ cancer

• Cohort 5: Any other HER2 IHC 3+ or FISH positive cancer Patients in Part 2 will receive the dose of study drug identified in Part 1 of the study. These patients will be followed to further evaluate the safety of ZW25 as well as to explore anti-tumour activity. Part 3, Combination Therapy Expansion: Patients with HER2-expressing breast or gastric/GEJ cancers will be treated with ZW25 in combination with one of several chemotherapy regimens including paclitaxel, capecitabine and vinorelbine.

View this trial on ClinicalTrials.gov