Imgatuzumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This study will evaluate the anti-tumor activity, safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of imgatuzumab, a monoclonal antibody against epidermal growth factor receptor (EGFR) with enhanced antibody-dependent cellular cytotoxicity (ADCC) in patients with advanced cutaneous squamous cell carcinoma (CSCC). Quality of life of patients treated with imgatuzumab will also be assessed.

Official Title
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Phase 2 Study of Imgatuzumab in Patients With Advanced Cutaneous Squamous Cell Carcinoma (I-PACE)

Conditions
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Cutaneous Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Imgatuzumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed diagnosis of CSCC CSCC of advanced stage Males or females at least 18 years of age at the time of consent Signed informed consent provided prior to any study procedures Ability to and willing to understand informed consent and comply with protocol requirements and procedures No more than two prior lines of systemic treatment for advanced disease Patients must have at least one lesion that is considered as measurable according to the Study Response Criteria Eastern Cooperative Oncology Group performance status 0 or 1 Adequate function of bone marrow, liver, kidneys Availability of tumor tissue sample (either an archival specimen or a fresh biopsy material) at Screening Key Exclusion Criteria: Prior systemic treatment for advanced disease with any anti-EGFR agent Active central nervous system metastasis Systemic anti-cancer therapy within five half-lives or two weeks, whichever is shorter, prior to first dose of the study drug Persistent toxicities from previous systemic anti-neoplastic treatments Wide-field radiotherapy within four weeks, or focal radiation for analgesic purpose or for lytic lesions at risk of fracture within two weeks prior to first dose of the study drug, or no recovery from side effects of such intervention Major surgery within four weeks prior to first dose of the study drug, or no recovery from side effects of such intervention Active infection requiring therapy Concomitant use of systemic steroids at dose of >10 mg of prednisone or its equivalent per day Known or suspected allergy/hypersensitivity to the study drug or any component of the study drug, other monoclonal antibodies, premedication medicines Concurrent participation in another investigational therapeutic clinical trial Pregnant or breast-feeding females Mental or medical conditions that prevent the patient from giving informed consent or participating in the trial Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with the study participation or the study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for enrollment in this study Note: Other protocol defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imgatuzumab monotherapy<br> | Drug: Imgatuzumab<br>* Imgatuzumab administered as an intravenous infusion on Day 1 and Day 8 of the first 21-day cycle, and on Day 1 of each subsequent 14-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) assessed by the Independent Central Review Committee (ICRC) according to the Study Response Criteria | Proportion of patients achieving Complete Response (CR) or Partial Response (PR) assessed by the ICRC according to the Study Response Criteria | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) assessed by the ICRC according to the Study Response Criteria | Proportion of patients achieving CR, PR or Stable Disease (SD) assessed by the ICRC according to the Study Response Criteria | Up to 24 months | 
| ORR assessed by the investigator according to the Study Response Criteria | Proportion of patients achieving CR or PR assessed by the investigator according to the Study Response Criteria | Up to 24 months | 
| DCR assessed by the investigator according to the Study Response Criteria | Proportion of patients achieving CR, PR or SD assessed by the investigator according to the Study Response Criteria | Up to 24 months | 
| Progression-free Survival (PFS) assessed by the ICRC | Time from date of start of treatment to date of the first progression documented by the ICRC | Up to 24 months | 
| Duration of Response (DoR) assessed by the ICRC | Time from date of first assessment of response (CR or PR) to date of the first progression documented by the ICRC | Up to 24 months | 
| Duration of Stable Disease (DoSD) assessed by the ICRC | Time from date of first assessment of SD to date of the first progression documented by the ICRC | Up to 24 months | 
| PFS assessed by the investigator | Time from date of start of treatment to date of the first progression documented by the investigator | Up to 24 months | 
| DoR assessed by the investigator | Time from date of first assessment of response (CR or PR) to date of the first progression documented by the investigator | Up to 24 months | 
| DoSD assessed by the investigator | Time from date of first assessment of SD to date of the first progression documented by the investigator | Up to 24 months | 
| ORR assessed by the ICRC according to the immune Response Evaluation Criteria in Solid Tumors (iRECIST) | Proportion of patients achieving CR or PR assessed by the ICRC according to the iRECIST | Up to 24 months | 
| ORR assessed by the investigator according to the iRECIST | Proportion of patients achieving CR or PR assessed by the investigator according to the iRECIST | Up to 24 months | 
| DCR assessed by the ICRC according to the iRECIST | Proportion of patients achieving CR, PR or SD assessed by the ICRC according to the iRECIST | Up to 24 months | 
| DCR assessed by the investigator according to the iRECIST | Proportion of patients achieving CR, PR or SD assessed by the investigator according to the iRECIST | Up to 24 months | 
| PFS assessed by the ICRC according to the iRECIST | Time from date of start of treatment to date of the first iRECIST progression documented by the ICRC | Up to 24 months | 
| PFS assessed by the investigator according to the iRECIST | Time from date of start of treatment to date of the first iRECIST progression documented by the investigator | Up to 24 months | 
| DoR assessed by the ICRC according to the iRECIST | Time from date of first assessment of response (CR or PR) to date of the first iRECIST progression documented by the ICRC | Up to 24 months | 
| DoR assessed by the investigator according to the iRECIST | Time from date of first assessment of response (CR or PR) to date of the first iRECIST progression documented by the investigator | Up to 24 months | 
| DoSD assessed by the ICRC according to the iRECIST | Time from date of first assessment of SD to date of the first iRECIST progression documented by the ICRC | Up to 24 months | 
| DoSD assessed by the investigator according to the iRECIST | Time from date of first assessment of SD to date of the first iRECIST progression documented by the investigator | Up to 24 months | 
| Incidence of Adverse Events | Safety and tolerability profile assessed by Common Terminology Criteria for Adverse Events v5.0 | Up to 24 months | 
| Frequency of dose interruptions and reductions | Safety and tolerability profile assessed by frequency of dose interruptions and reductions | Up to 24 months | 
| Duration of dose interruptions and reductions | Safety and tolerability profile assessed by duration of dose interruptions and reductions | Up to 24 months | 
| Concentrations of imgatuzumab-reactive antibodies | Immunogenicity profile characterized by concentrations of imgatuzumab-reactive antibodies | Up to 24 months | 
| Maximum observed concentration (C[max]) | Pharmacokinetic profile characterized by the maximum observed concentration (C[max]) of imgatuzumab | Up to 24 months | 
| Area under the curve (AUC) | Pharmacokinetic profile characterized by the area under the curve (AUC) of imgatuzumab | Up to 24 months | 
| Terminal half-life (t[1/2]) | Pharmacokinetic profile characterized by the terminal half-life (t[1/2]) of imgatuzumab | Up to 24 months | 
| Time to maximum concentration (Tmax) | Pharmacokinetic profile characterized by the time to maximum concentration (Tmax) of imgatuzumab | Up to 24 months | 
| Change in scores of patient-reported outcomes | Quality of life assessed by change in scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores are transformed linearly to a zero to 100 scale. A higher score on the functional scale and the global Health related Quality of Life indicates better functioning | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Cutaneous Squamous Cell Carcinoma, Epidermal Growth Factor Receptor, Antibody-dependent Cellular Cytotoxicity, Carcinoma