Clinical Trial Evaluating the Activity of Zanidatamab for the Treatment of Patients With Solid Tumors With an Alteration of the HER2 Gene.
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNICANCER
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Single group
Treatments tested in this trial
Zanidatamab
DrugSingle 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.
Treatment groups
105 Participants
are divided into 1 treatment groupGroup A: zanidatamabExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
From Baseline to disease progression (up to 28 months)Secondary outcomes
1
Confirmed ORR by the BICR
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
Time frame
From baseline to the progression (up to 28 months)2
Duration of Response (DoR)
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. DoR will be provided as assessed by investigators and as adjudicated by the BICR.
Time frame
From baseline to the progression (up to 28 months)3
Progression Free Survival (PFS)
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.
Time frame
From baseline to disease progression or death (up to 28 months)4
Clinical Benefit Rate (CBR)
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.
Time frame
From baseline to the progression (up to 28 months)Sponsors and contacts
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Source ClinicalTrials.gov