NCT02892123

Brief Summary

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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
279

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2016

Longer than P75 for phase_1

Geographic Reach
3 countries

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 23, 2016

Completed
16 days until next milestone

First Posted

Study publicly available on registry

September 8, 2016

Completed
22 days until next milestone

Study Start

First participant enrolled

September 30, 2016

Completed
8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2024

Completed
Last Updated

November 27, 2024

Status Verified

November 1, 2024

Enrollment Period

8.1 years

First QC Date

August 23, 2016

Last Update Submit

November 25, 2024

Conditions

HER2-expressing Cancers

Keywords

HER2Bispecific antibodyBiparatopic antibodyImmunotherapyBreast cancerGastroesophageal adenocarcinoma (GEA)Gastric cancerGastroesophageal junction (GEJ) cancerOvarian cancerNon-small cell lung cancer (NSCLC)ChemotherapyPaclitaxelCapecitabineVinorelbineTucatinib

Outcome Measures

Primary Outcomes (2)

  • The proportion of patients who experience dose-limiting toxicities (DLTs) (Part 1)

    Up to 8 months

  • The proportion patients who experience laboratory abnormalities and/or adverse events as defined by CTCAE v4.03 that are related to treatment (Parts 2 and 3)

    Throughout the duration of the study; up to 2 years

Secondary Outcomes (5)

  • Serum concentrations of ZW25

    Throughout the duration of the study; up to 2 years

  • The proportion of patients who develop detectable anti-drug antibodies

    Throughout the duration of the study; up to 2 years

  • The proportion of patients with an objective response (partial response or complete response) as defined by RECIST 1.1 criteria

    Throughout the duration of the study; up to 2 years

  • Progression free survival as defined by RECIST 1.1 criteria

    Throughout the duration of the study; up to 2 years

  • The proportion patients who experience laboratory abnormalities and/or adverse events as defined by CTCAE v4.03 that are related to treatment (Part 1)

    Throughout the duration of the study; up to 2 years

Study Arms (1)

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy

EXPERIMENTAL
Drug: ZW25 (Zanidatamab)Drug: PaclitaxelDrug: CapecitabineDrug: VinorelbineDrug: Tucatinib

Interventions

ZW25 (Zanidatamab)DRUG

ZW25 administered IV once weekly, once every 2 weeks, or once every 3 weeks. Part 1: in multiple increasing doses; Part 2: ZW25 given at the MTD, OBD, or an RD identified in Part 1; Part 3: ZW25 given at the MTD, OBD, or an RD combined with one of the following selected drug combination:

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy
PaclitaxelDRUG

Combination therapy with ZW25 - Part 3 Treatment Groups 1 and 4

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy
CapecitabineDRUG

Combination therapy with ZW25 - Part 3 Treatment Groups 2 and 5

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy
VinorelbineDRUG

Combination therapy with ZW25 - Part 3 Treatment Groups 3 and 6

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy
TucatinibDRUG

Combination therapy with ZW25 and Capecitabine - Part 3 Treatment Group 7

ZW25 (Zanidatamab) Monotherapy and ZW25 Combination Therapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

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:
  • +28 more criteria

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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

USC/Norris Cancer Center

Los Angeles, California, 90033, United States

Location

Hoag Family Cancer Institute

Newport Beach, California, 92663, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Sarah Cannon - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

University of Ottawa

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Related Publications (1)

  • Meric-Bernstam F, Beeram M, Hamilton E, Oh DY, Hanna DL, Kang YK, Elimova E, Chaves J, Goodwin R, Lee J, Nabell L, Rha SY, Mayordomo J, El-Khoueiry A, Pant S, Raghav K, Kim JW, Patnaik A, Gray T, Davies R, Ozog MA, Woolery J, Lee KW. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 2022 Dec;23(12):1558-1570. doi: 10.1016/S1470-2045(22)00621-0. Epub 2022 Nov 16.

    PMID: 36400106DERIVED

MeSH Terms

Conditions

Breast NeoplasmsStomach NeoplasmsNeoplasmsOvarian NeoplasmsCarcinoma, Non-Small-Cell Lung

Interventions

zanidatamabPaclitaxelCapecitabineVinorelbinetucatinib

Condition Hierarchy (Ancestors)

Neoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizines

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

August 23, 2016

First Posted

September 8, 2016

Study Start

September 30, 2016

Primary Completion

October 31, 2024

Study Completion

October 31, 2024

Last Updated

November 27, 2024

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will not share

Locations

US(9)CA(3)KR(5)