Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene.

NCT07192068 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-GMP-25052025-522169-31-00
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

Alterations in the HER2 gene are involved in the development of cancer. These abnormalities are found at highly variable rates (from approximately 2% to 60%) in cancers of the lung, breast, stomach, bile ducts, salivary glands, colon, endometrium, uterus, bladder, bones, blood, etc. Zanidatamab is an anti-cancer drug that acts on cells with alterations in the HER2 gene. It is used in Europe to treat people with bile duct cancer. However, in various clinical trials, zanidatamab has shown promising activity in a few patients with different cancers that have a HER2 gene alteration. This treatment could therefore be effective in several types of cancer once this gene alteration is detected. The primary objective is to evaluate the efficacy of zanidatamab in patients with cancer in one of the following locations: endometrium, colorectal, head and neck, sarcoma or lung cancer. Efficacy will be measured by the number of patients in whom a reduction in tumour size was observed. All patients included in the study will receive zanidatamab by intravenous infusion every 3 weeks. Treatment will continue as long as there is a benefit (stabilisation or regression of the disease). During treatment, participants will visit the hospital regularly for medical consultations to:

• assess and treat potential adverse effects of zanidatamab. A dose reduction may be applied to improve tolerance.
• monitor disease progression using scans and/or MRI, performed every 6 weeks for the first 18 months of treatment and then every 12 weeks. After treatment is stopped (due to intolerance or disease progression), patients will be monitored according to hospital practices until the end of the trial, i.e. for 1 to 4 years, depending on when they were included in the clinical trial.

Conditions

Sarcoma; Head &Amp; Neck Cancer; Colorectal Carcinoma; Endometrial; Non-Small Cell Lung Cancer

Keywords

zanidatamab; HER2 mutant; HER2-IHC3+

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (ORR) by investigator

  Confirmed Objective Response Rate (ORR) for each cohort, based on best overall response, defined as the percentage of patients with a complete response (CR) or partial response (PR) during treatment or follow-up, assessed according to RECIST1.1, by investigator assessment and confirmed by a follow-up scan at ≥ 4 weeks from first response assessment.

  From Baseline to disease progression (up to 28 months)

Secondary Outcomes (6)

• Confirmed ORR by the BICR

  From baseline to the progression (up to 28 months)

• Duration of Response (DoR)

  From baseline to the progression (up to 28 months)

• Progression Free Survival (PFS)

  From baseline to disease progression or death (up to 28 months)

• Clinical Benefit Rate (CBR)

  From baseline to the progression (up to 28 months)

• Overall Survival (OS)

  From baseline to death (up to 52 months)

Study Arms (1)

zanidatamab

EXPERIMENTAL

Single arm study where the experimental regimen used for all patients will be zanidatamab, administered intravenously every 3 weeks : * Patients \<70 kg: 1800 mg IV Q3W on Day 1 of each 21-day cycle * Patients ≥70 kg: 2400 mg IV Q3W on Day 1 of each 21-day cycle.

Drug: Zanidatamab

Interventions

Zanidatamab DRUG

Single arm study where the experimental regimen used for all patients will be zanidatamab, administered intravenously every 3 weeks : * Patients \<70 kg: 1800 mg IV Q3W on Day 1 of each 21-day cycle * Patients ≥70 kg: 2400 mg IV Q3W on Day 1 of each 21-day cycle.

zanidatamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed endometrial, colorectal, head \& neck, non-small cell lung cancer (NSCLC), or sarcoma
• Patient with progressive, unresectable and/or advanced or metastatic disease harboring a locally performed, centrally reviewed HER2-overexpressing (IHC 3+ exclusively) for endometrial, colorectal, head \& neck cancers, or sarcoma or a HER2 activating mutation for NSCLC, determined on tissue (see Section 7.1.2 of the protocol)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patient who progressed at least after 1 line of therapy, for whom there is no other standard therapeutic option available
• Patient with a HER2 alteration covered by a standard marketed indication for any HER2 targeting therapy should be included after standard anti-HER2 strategy has been exhausted.
• Estimated life expectancy \>3 months
• Measurable disease according to RECIST1.1, whatever the disease location. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been clearly demonstrated in the lesion
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥75 × 10⁹/L, and haemoglobin ≥9 g/dL. Transfusion is allowed with a 2-week washout period before treatment initiation
• Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range (total bilirubin ≤3.0 ULN when the patient has documented Gilbert syndrome or liver metastasis), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN (AST and ALT ≤5 ULN when documented tumor liver involvement)
• Normal prothrombin time (PT) \>70% and partial thromboplastin time (PTT), except for patient who uses anticoagulants
• Adequate renal function: estimated serum creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
• Man, and woman of childbearing potential must agree to use highly effective contraception for the duration of trial participation and as required after completing study treatment (refer to Table 6 in the protocol). Man must also agree to not donate sperm and women must agree to not donate oocytes during the specified period
• Woman of childbearing potential must have a negative serum pregnancy test performed within 3 days before the date of treatment initiation
• Availability of a suitable archived FFPE sample of primary or metastatic tumor tissue (archived FFPE is \<2 years old (desirable), maximum 5 years (accepted), buffered formalin fixed only. Fine-needle aspiration (cytology samples) and biopsies from sites of bone metastases are not acceptable) or patient accepts an optional biopsy under study
• Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, specimen sampling for research, and other study procedures

You may not qualify if:

• Patient, in the judgment of the investigator, who should be included in another recruiting study assessing an anti-HER2 therapy (including zanidatamab)
• Patient who received prior treatment with HER2-directed therapy unless marketed for the study cohort indication.
• Other primary malignancies within 3 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivor, who has undergone potentially curative therapy for a prior malignancy, has no evidence of that disease for 4 years or more and is deemed at negligible risk for recurrence, is eligible for the trial
• Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement not related to lung metastases (e.g. rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
• Prior pneumonectomy
• Patient with any condition or any evidence of severe or uncontrolled systemic diseases (e.g. active bleeding diatheses, active infection, or psychiatric illness) which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required for eligibility
• History of myocardial infarction or unstable angina within 6 months prior to enrolment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure
• Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Patient with clinically inactive or treated brain metastases who are asymptomatic (i.e. without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the study. Patient must have a stable neurologic status and no evidence of radiographic progression for at least 2 weeks prior to first zanidatamab dosing
• Patient with evidence of any leptomeningeal disease. If leptomeningeal disease has been reported radiographically on baseline magnetic resonance imaging (MRI), but is not suspected clinically by the investigator, the subject must be free of neurological symptoms.
• Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease
• Patient with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤1 or baseline, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Patient with chronic Grade 2 toxicities may be enrolled at the discretion of the investigator after consultation and approval by the coordinating investigator.
• Patient receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy within 2 weeks of first zanidatamab dosing unless otherwise approved by the coordinating investigator. Patient who requires use of bronchodilators, inhaled or topical or ocular steroids, or local steroid injections may be included in the study
• Treatment with anthracyclines within 90 days before first dose of zanidatamab and/or total lifetime load exceeding 360 mg/m2 doxorubicin or equivalent
• A history of life-threatening hypersensitivity to monoclonal antibodies or recombinant proteins
• Woman who is pregnant or breast-feeding

Sponsors & Collaborators

• UNICANCER: lead
• Jazz Pharmaceuticals: collaborator
• National Cancer Institute, France: collaborator

Study Sites (4)

Institut de Cancérologie de l'Ouest

Angers, France

ACTIVE NOT RECRUITING

Chu Timone

Marseille, France

RECRUITING

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

ACTIVE NOT RECRUITING

Gustave Roussy

Villejuif, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Sarcoma; Head and Neck Neoplasms; Colorectal Neoplasms

Interventions

zanidatamab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Barbara PISTILLI, Dr

  Gustave Roussy, VILLEJUIF

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Céline MAHIER AIT OUKHATAR

CONTACT

+33 (0)6 17 51 34 29; c-mahier@unicancer.fr

Marta JIMENEZ

CONTACT

m-jimenez@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2025
• First Posted: September 25, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): March 13, 2028
• Study Completion (Estimated): June 24, 2030
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)