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HER2-expressing CancersPhase 1NCT02892123

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

A Phase 1 study testing ZW25 (Zanidatamab), Paclitaxel and Capecitabine in people with HER2-expressing Cancers, run by Jazz Pharmaceuticals at 17 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER2-expressing Cancers
What is being tested?
ZW25 (Zanidatamab), Paclitaxel and Capecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
279 participants
Where
17 sitesin 3 countries
Study dates
30 Sep 2016to 31 Oct 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 43Show fewer
  • 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
  • HER2 IHC 3+ or IHC 2+/FISH+ breast cancer patients (TGs 1, 2, or 3) 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 (TGs 1 or 2) who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
  • HER2 IHC 3+ or IHC 2+/FISH+ GEA patients who have received prior therapy with trastuzumab (TG4; ZW25 + paclitaxel)
  • HER2 IHC 3+, IHC 2+/FISH+ or otherwise HER2-positive per ASCO/CAP guidelines breast cancer patients who have received prior therapy with trastuzumab, pertuzumab, and T-DM1 (TG5; ZW25 + capecitabine)
  • HER2 IHC 3+, IHC 2+/FISH+ or otherwise HER2-positive per ASCO/CAP guidelines breast cancer patients (TG6) who have received prior therapy with trastuzumab, pertuzumab, and T-DM1
  • HER2 IHC 3+, IHC2+/FISH+, or otherwise HER2-positive per ASCO/CAP guidelines breast cancer patients (TG7) who have received prior therapy with trastuzumab, pertuzumab, and T-DM1
  • HER2 IHC 3+, IHC 2+/FISH+, or otherwise HER2-positive per ASCO/CAP guidelines breast cancer patients (TG8) who have received prior therapy with trastuzumab, pertuzumab, and T-DM1
  • ≥ 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 - 7, and Parts 2 and 3: measurable disease (target lesions) per RECIST version 1.1
  • Able to provide tumor sample (fresh or archived)
  • For Part 3 TGs 7 and 8 only - based on screening brain MRI, patients must have one of the following:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment
  • Previously treated brain metastases that are either stable since treatment or have progressed since prior local CNS therapy, provided there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator

Who cannot join

  • 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)
Show all 19Show fewer
  • 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

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

United States9 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • University of Alabama

    Birmingham, Alabama, 35294

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • USC/Norris Cancer Center

    Los Angeles, California, 90033

  • Sarah Cannon - Tennessee Oncology

    Nashville, Tennessee, 37203

  • Hoag Family Cancer Institute

    Newport Beach, California, 92663

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

Other trials in United States

South Korea5 sites

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 13620

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Canada3 sites

  • Jewish General Hospital

    Montreal, Quebec, H3T1E2

  • University of Ottawa

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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

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).

Read the detailed description

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, vinorelbine, or capecitabine and tucatinib. 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.

Being tested
ZW25 (Zanidatamab), Paclitaxel, Capecitabine, Vinorelbine, Tucatinib
Keywords
HER2, Bispecific antibody, Biparatopic antibody, Immunotherapy, Breast cancer, Gastroesophageal adenocarcinoma (GEA), Gastric cancer, Gastroesophageal junction (GEJ) cancer, Ovarian cancer, Non-small cell lung cancer (NSCLC), Chemotherapy, Paclitaxel, Capecitabine, Vinorelbine, Tucatinib
Medical subject headings
Breast Neoplasms, Stomach Neoplasms, Neoplasms, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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:

  • PaclitaxelDrug

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

  • CapecitabineDrug

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

  • VinorelbineDrug

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

  • TucatinibDrug

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

  • TucatinibDrug

    Combination therapy with ZW25 - Part 3 Treatment Group 8 (may be opened if recommended by the Safety Monitoring Committee and/or the sponsor)

Study groups in NCT02892123
Study groupRoleWhat they receive
ZW25 (Zanidatamab) Monotherapy and ZW25 Combination TherapyExperimentalNot described
Receives: Drug: ZW25 (Zanidatamab); Drug: Paclitaxel; Drug: Capecitabine; Drug: Vinorelbine; Drug: Tucatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 8 months

  2. 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)

    Measured: Throughout the duration of the study; up to 2 years

Secondary outcomes (5)

  1. Serum concentrations of ZW25

    Measured: Throughout the duration of the study; up to 2 years

  2. The proportion of patients who develop detectable anti-drug antibodies

    Measured: Throughout the duration of the study; up to 2 years

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

    Measured: Throughout the duration of the study; up to 2 years

  4. Progression free survival as defined by RECIST 1.1 criteria

    Measured: Throughout the duration of the study; up to 2 years

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

    Measured: Throughout the duration of the study; up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2016 (estimated)
  2. Study start30 Sep 2016
  3. Primary completion31 Oct 2024
  4. Study completion31 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
279 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02892123
Sponsor's protocol ID
ZWI-ZW25-101
Status last verified
Nov 2024
First submitted
23 Aug 2016
Last updated
27 Nov 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
No
Expanded access
Available

Publications

  • 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.

    PubMed 36400106

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ZW25 (Zanidatamab), Paclitaxel and Capecitabine in people with HER2-expressing Cancers, run by Jazz Pharmaceuticals at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, South Korea, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients who experience dose-limiting toxicities (DLTs) (Part 1) (time frame: Up to 8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02892123, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2024.

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