ZANIDATAMAB for Endometrial cancer | Colorectal cancer | Head and neck cancer | Sarcoma | Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Histologically or cytologically confirmed endometrial, colorectal, head & neck, non-small cell lung cancer (NSCLC), or sarcoma\n- 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)\n- Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 14 days before inclusion\n- Normal prothrombin time (PT) >70% and partial thromboplastin time (PTT), except for patient who uses anticoagulants\n- Adequate renal function: estimated serum creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula\n- 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\n- Woman of childbearing potential must have a negative serum pregnancy test performed within 3 days before the date of treatment initiation\n- 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\n- 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\n- Affiliated to a social security system\n- Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient’s consent.\n- 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)\n- Age ≥ 18 years at inclusion\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2\n- Patient who progressed at least after 1 line of therapy, for whom there is no other standard therapeutic option available\n- 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.\n- Estimated life expectancy >3 months\n- 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\n- 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"}

Exclusion criteria

• {"criterion_text":"- Patient, in the judgment of the investigator, who should be included in another recruiting study assessing an anti-HER2 therapy (including zanidatamab)\n- Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease\n- 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.\n- 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\n- Treatment with anthracyclines within 90 days before first dose of zanidatamab and/or total lifetime load exceeding 360 mg/m2 doxorubicin or equivalent\n- A history of life-threatening hypersensitivity to monoclonal antibodies or recombinant proteins\n- Woman who is pregnant or breast-feeding\n- Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable\n- Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons\n- Individual deprived of liberty or placed under protective custody or guardianship.\n- Patient who received prior treatment with HER2-directed therapy unless marketed for the study cohort indication.\n- 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\n- Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement not related to lung metastases (e.g. rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)\n- Prior pneumonectomy\n- 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\n- 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\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"ORR defined as percentage of patients with a CR or 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."}

Secondary endpoints

• {"endpoint_text":"- Confirmed ORR for each cohort, based on best overall response as adjudicated by the BICR, defined as the percentage of patients with a CR or PR during treatment or follow-up, assessed according to RECIST1.1 and confirmed by a follow-up scan at ≥ 4 weeks from first response assessment .","definition_or_measurement_approach":"ORR adjudicated by Blinded Independent Central Review (BICR) per RECIST1.1, confirmed by follow-up scan ≥4 weeks from first response assessment."}
• {"endpoint_text":"- Duration of Response (DoR) for each cohort will be evaluated in patients with either a CR or PR. DoR is defined as the time from the first assessment of a confirmed CR or PR until the date of the first occurrence of progressive disease (PD) according to RECIST1.1 or death from any cause (if death occurs within predefined period), whichever occurs first. At the time of analysis, a patient alive and without disease progression will be censored at the date of the last valid tumor assessment.","definition_or_measurement_approach":"DoR measured from first confirmed CR or PR to date of first PD per RECIST1.1 or death; censoring at last valid tumor assessment if no progression."}
• {"endpoint_text":"- Progression Free Survival (PFS) for each cohort is defined as the time from study registration until disease progression (per RECIST1.1) or death from any cause, whichever occurs first. At the time of analysis, a patient alive and without disease progression will be censored at the date of the last valid tumor assessment. PFS will be provided as assessed by investigators and as adjudicated by the BICR.","definition_or_measurement_approach":"PFS measured from study registration to progression per RECIST1.1 or death; assessed by investigators and adjudicated by BICR; censoring at last valid tumor assessment if no progression."}
• {"endpoint_text":"- Clinical Benefit Rate (CBR) for each cohort is defined as the percentage of patients with a CR or PR or stable disease (SD) for more than 16 weeks from inclusion assessed according to RECIST1.1. CBR will be provided as assessed by investigators and as adjudicated by the BICR.","definition_or_measurement_approach":"CBR = percentage of patients with CR or PR or SD lasting >16 weeks from inclusion per RECIST1.1; assessed by investigators and BICR."}
• {"endpoint_text":"- Overall Survival (OS) for each cohort is defined as the time from study registration until death from any cause. Patients who are alive at last follow-up will be censored at this date.","definition_or_measurement_approach":"OS measured from study registration to death from any cause; censoring at last follow-up for survivors."}
• {"endpoint_text":"- The safety will be evaluated according to the incidence of adverse events (AEs) graded by NCI-CTCAE v5.0, per cohort and overall.","definition_or_measurement_approach":"Safety assessed by incidence and grade of AEs per NCI-CTCAE v5.0, reported per cohort and overall."}

France

Earliest CTIS Part Ii Submission Date

18-08-2025

Latest Decision Or Authorization Date

01-10-2025

Processing Time Days

44

Number Of Sites

19

Number Of Participants

105

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}