Trial of ZW25 in Patients With Advanced HER2-expressing Cancers

Status: Active

Description

This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 by itself and combined with selected chemotherapy agents in patients with locally advanced (unresectable) and / or metastatic human epidermal growth factor receptor 2 (HER2)-expressing cancers. This study will also the evaluate the way the body absorbs, distributes, and eliminates ZW25 (pharmacokinetics or PK).

Eligibility Criteria

Inclusion Criteria

  • HER2-expressing cancer as follows: Part 1:
  • Cohorts 1 - 3: Any locally advanced (unresectable) and/or metastatic HER2-expressing (HER2 1+, 2+, or 3+ by IHC) cancer (including but not limited to breast, gastric, ovarian, colorectal and non-small cell lung) that has progressed after receipt of all therapies known to confer clinical benefit
  • Cohorts 4 - 6:
  • HER2 IHC 2+ /FISH- breast cancer or gastroesophagel adenocarcinoma (GEA)
  • HER2 IHC 3+ or HER2 IHC 2+ /FISH+ breast cancer or GEA
  • Any other HER2 IHC 3+ or FISH+ cancer
  • HER2-overexpressing (3+ by IHC) or HER2-2+ and FISH+ breast cancer must have progressed after prior treatment with trastuzumab, pertuzumab, and T-DM1
  • HER2-overexpressing (3+ by IHC) or HER2-2+ and FISH+ GEA must have progressed after prior treatment with trastuzumab
  • Patients with colorectal cancer must be KRAS wild-type
  • Patients with NSCLC must have ALK wild-type, EGFR wild-type, and ROS1 fusion negative as determined by standard methods
  • Cohort 7 (only at selected sites): HER2 IHC 3+, HER2 IHC 2+ /FISH+, or HER2 IHC 2+ /FISH- breast cancer Part 2: Locally advanced (unresectable) and/or metastatic cancer that has progressed after receipt of all therapies known to confer clinical benefit (unless ineligible to receive a specific therapy) as follows:
  • Cohort 1: HER2 IHC 2+/FISH- breast cancer
  • Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH+ breast cancer
  • Cohort 3: HER2 IHC 2+/FISH- GEA
  • Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH+ GEA
  • Cohort 5: Any other HER2 IHC 3+ or IHC 2+/FISH+ cancer, including the following:
  • Cohort 5a: HER2 IHC 3+ or IHC 2+/FISH+ GI cancers other than GEA (patients with colorectal cancer must be KRAS wild-type.)
  • Cohort 5b: Any other HER2 IHC 3+ or IHC 2+/FISH+ solid tumor types that are not breast or GI cancers (patients with NSCLC must have ALK wild-type, EGFR wild-type, and ROS1 fusion negative as determined by standard methods; patients with ovarian cancers must be KRAS wild type.) Part 3: Locally advanced (unresectable) and/or metastatic cancer as follows:
  • HER2 IHC 1+ or IHC2+/FISH- breast cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
  • HER2 IHC 3+ or IHC 2+/FISH+ breast cancer patients who have received prior therapy with trastuzumab, pertuzumab, and T-DM1, at least 1 and no more than 3 prior systemic chemotherapy regimens
  • HER2 IHC 2+ or 3+ FISH+ or FISH- GEA patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
  • ≥ 18 years of age
  • ECOG performance status of 0 or 1
  • Life expectancy of at least 3 months per the investigator's assessment.
  • Adequate organ function
  • Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal
  • For Part 1 Cohorts 1 - 3: evaluable disease (target or non-target lesions) per RECIST version 1.1. For Part 1 Cohorts 4 - 6, and Parts 2 and 3: measurable disease (target lesions) per RECIST version 1.1
  • Able to provide tumor sample (fresh or archived)

Exclusion Criteria

  • Experimental therapies within 4 weeks before first ZW25 dosing
  • Treatment with other cancer therapy not otherwise specified within 4 weeks before ZW25 dosing
  • Anthracyclines within 90 days before first ZW25 dosing or lifetime load exceeding 300 mg/m² adriamycin or equivalent
  • Trastuzumab, pertuzumab, lapatinib, or T‑DM1 within 3 weeks before first ZW25 dosing
  • Untreated brain metastases (patients with treated brain mets who are off steroids and are stable for at least 1 month at the time of screening are eligible)
  • Pregnant or breast-feeding women
  • History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in drug formulation
  • Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
  • Peripheral neuropathy >Grade 2
  • Clinically significant interstitial lung disease
  • Known active hepatitis B or C or known infection with HIV
  • Immunosuppressive corticosteroids equivalent to >15mg/day of prednisone within 2 weeks before first ZW25 dose
  • QTc Fridericia (QTcF) >450 ms
  • Having clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic CHF
  • Having known myocardial infarction or unstable angina within 6 months before first ZW25 dosing

Locations & Contacts

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Christos Vaklavas
Phone: 205-934-5677
Email: cvaklavas@uabmc.edu

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Jubilee Grace P. Acap
Phone: 323-409-4367
Email: jubilee.acap@med.usc.edu

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

Part 1 of the study will evaluate increasing doses of ZW25 to find the highest dose of ZW25 that does not cause unacceptable side effects (maximum-tolerated dose or MTD), the lowest safe dose with the highest rate of effectiveness (optimal biological dose or OBD), and/or other recommended dosages (RDs) of ZW25 in up to 7 dose-specific cohorts. Eligible patients include those with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after receipt of all therapies known to confer clinical benefit (or ineligible to receive therapy). Part 2 of the study will further evaluate the safety, tolerability, and efficacy of ZW25 in patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after receipt of all therapies known to confer clinical benefit (or ineligible to receive therapy) in up to 5 separate disease-specific cohorts. Part 3 of the study will evaluate the safety, tolerability, and efficacy of ZW25 combined with selected chemotherapy agents, including paclitaxel, capecitabine, or vinorelbine. Patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after at least 1 and no more than 3 prior systemic chemotherapy regimens will be evaluated in this part of the study.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Zymeworks Inc.

Trial IDs

Primary ID ZWI-ZW25-101
Secondary IDs NCI-2017-01210
Clinicaltrials.gov ID NCT02892123