Evidence map›Paper›PMID 40341383›Full record

ArticleNature communications2025

Zanidatamab monotherapy or combined with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma: a phase 1 trial.

Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh and 6 more

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02892123 (Phase I Trial of ZW25 in Patients With Locally Advanced), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02892123 phase1completednot on this map

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

TypeinterventionalSponsorJazz PharmaceuticalsRan2016 to 2024Enrolled279ConditionsHER2-expressing CancersArmsZW25 (Zanidatamab), Paclitaxel, Capecitabine, Vinorelbine, Tucatinib
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Funda Meric-BernstamDepartment of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. fmeric@mdanderson.org.ORCID http://orcid.org/0000-0001-6816-6072
Sun Young RhaYonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0002-2512-4531
Erika HamiltonSarah Cannon Research Institute, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-1911-0336
Yoon-Koo KangAsan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Diana L HannaUSC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Syma IqbalUSC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Keun-Wook LeeDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Jeeyun LeeSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0002-4911-6165
Muralidhar BeeramSTART Center for Cancer Care, San Antonio, TX, USA.
Do-Youn OhSeoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.
Jorge ChavesNorthwest Medical Specialties, Tacoma, WA, USA.
Rachel A GoodwinOttawa Hospital Cancer Centre, Ottawa Hospital Research Centre, Ottawa, ON, Canada.
Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9946-0629
Lin YangJazz Pharmaceuticals, Palo Alto, CA, USA.
Rajen OzaJazz Pharmaceuticals, Palo Alto, CA, USA.
Elena ElimovaPrincess Margaret Cancer Centre, Toronto, ON, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, 93%; combination therapy, 95%). With monotherapy, 69% of patients had any-grade treatment-related AEs (TRAEs); 17% had grade ≥ 3 TRAEs. The most common any-grade TRAEs were diarrhea (41%) and infusion-related reactions (24%). With combination therapy, 98% of patients had any-grade TRAEs; 51% had grade ≥ 3 TRAEs. The most common any-grade TRAEs were diarrhea (68%) and fatigue (44%). Confirmed ORR was 32.1% (95% confidence interval [CI] 15.9-52.4) with monotherapy and 48.6% (95% CI 31.9-65.6) with combination therapy. In heavily pre-treated patients with HER2-expressing GEA, zanidatamab ± chemotherapy had a manageable safety profile and promising antitumor activity.

Indexed as

AdenocarcinomaAntibodies, BispecificAntineoplastic Combined Chemotherapy ProtocolsErb-b2 Receptor Tyrosine KinasesEsophageal NeoplasmsStomach NeoplasmsAdultAgedAged, 80 and overCapecitabineEsophagogastric JunctionFemaleHumansMaleMiddle AgedPaclitaxelAntibodies, BispecificCapecitabineERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPaclitaxelzanidatamab

Identifiers

PMID40341383
PMCPMC12062219

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.