Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers

Completed · Phase 1

Conditions studied: HER2-expressing Cancers

In brief

This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 (zanidatamab) 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).

Key facts

Study ID

NCT02892123

Run by

Jazz Pharmaceuticals

People needed

279

Starts

2016-09-30

Expected to finish

2024-10-31

Last updated by the study team

2024-11-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Cohort 4:
• HER2 IHC 2+ /FISH- breast cancer or gastroesophageal 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
• Cohorts 5 - 6: HER2 IHC 3+ or HER2 IHC 2+ /FISH+ GEA must have progressed after prior treatment with trastuzumab
• Cohort 7 (only at selected sites): HER2 IHC 3+, HER2 IHC 2+ /FISH+, or HER2 IHC 2+ /FISH- breast cancer must have progressed after prior treatment with trastuzumab, pertuzumab, and T-DM1
• 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 (TGs 1, 2, or 3) who have received at least 1 and no more than 3 prior systemic chemotherapy regimens

You may not qualify if…

• 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
• Patients in Part 3 TG4 must not have received prior taxanes
• Patients in Part 3 TG5 must not have received prior capecitabine for metastatic disease or received any prior fam-trastuzumab deruxtecan-nxki (DS-8201a)
• With the exception of Part 3 TGs 7 and 8, 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
• Patients in Part 3 TG7 must not have received prior capecitabine or tucatinib for metastatic disease
• Patients in Part 3 TG8 must not have received prior tucatinib therapy for metastatic disease

Where it is running

• University of Alabama — Birmingham, Alabama, United States
• USC/Norris Cancer Center — Los Angeles, California, United States
• Hoag Family Cancer Institute — Newport Beach, California, United States
• University of Colorado Cancer Center — Aurora, Colorado, United States
• Rush University Medical Center — Chicago, Illinois, United States
• Sarah Cannon - Tennessee Oncology — Nashville, Tennessee, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• South Texas Accelerated Research Therapeutics (START) — San Antonio, Texas, United States
• Northwest Medical Specialties — Tacoma, Washington, United States
• University of Ottawa — Ottawa, Ontario, Canada
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada
• Jewish General Hospital — Montreal, Quebec, Canada
• Seoul National University Bundang Hospital — Seongnam-si, Gyeonggi-do, South Korea
• Seoul National University Hospital — Seoul, South Korea
• Severance Hospital — Seoul, South Korea
• Asan Medical Center — Seoul, South Korea
• Samsung Medical Center — Seoul, South Korea

Full record on ClinicalTrials.gov

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