Widening Treatment Options Among Adult Patients With HER2-overexpressing or Mutant Solid Cancers.
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.
• 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)
• Age ≥ 18 years at inclusion
• 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)
⁃ 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
⁃ 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
⁃ Affiliated to a social security system
⁃ 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.