Overview

Condition carcinoma, merkel cell
Treatment avelumab
Phase phase 2
Target PD-1
Sponsor EMD Serono
Start date June 2014
End date March 2016
Trial size 138 participants
Trial identifier NCT02155647, 100070-003, 2014-000445-79

Summary

This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in subjects with metastatic Merkel cell carcinoma (MCC).

Recruiting in the following locations…

United States California, Florida, Massachusetts, Missouri, New Jersey, and Pennsylvania
Other Countries France and Germany

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
avelumab anti-PD-L1
Subjects will receive intravenous infusion of avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or study drug.

Primary Outcomes

Measure
Part A: Confirmed Best Overall Response (BOR)
time frame: Up to 3 years
Part B: Durable Response
time frame: Up to 3 years

Secondary Outcomes

Measure
Part A: Duration of response
time frame: Up to 3 years
Part A: Progression-Free Survival (PFS) Time
time frame: Up to 3 years
Part A: Overall Survival (OS) Time
time frame: Up to 3 years
Part A: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
time frame: Baseline up to 90 days after last dose administration
Part A:Number of subjects with anti-avelumab antibodies
time frame: Up to 3 years
Part A: Concentration at the end of infusion on Day 1
time frame: Day 1
Part A: Trough concentrations
time frame: Day 15, 29, 43, 85, 127, 169
Part B: Confirmed Best Overall Response (BOR)
time frame: Up to 3 years
Part B: Duration of response
time frame: Up to 3 years
Part B: Progression-Free Survival (PFS) Time
time frame: up to 3 years
Part B: Overall Survival (OS) Time
time frame: up to 3 years
Part B: Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
time frame: Baseline up to 90 days after last dose administration
Part B: Number of subjects with anti-avelumab antibodies
time frame: up to 3 years
Part B: Concentration at the end of infusion on Day 1
time frame: Day 1
Part B: Trough concentrations
time frame: Day 15, 29, 43, 85, 127, 169
Part A: Number of Subjects With Response Status According to RECIST 1.1 as Determined by an IERC
time frame: Month 6, Month 12
Part B: Number of Subjects With Response Status According to RECIST 1.1 as Determined by an IERC
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - • Signed written informed consent - Age 18 years and above - Histologically proven MCC as defined in the protocol - For Part A - Progressive disease after receiving 1 line of chemotherapy for metastatic MCC - For Part B - Subjects must not have received any prior systemic treatment for metastatic MCC. Prior chemotherapy treatment in the adjuvant setting (no clinically detectable disease; no metastatic disease) is allowable if the end of treatment occurred at least 6 months prior to study start) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 - Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST Version 1.1 (including skin lesions) - Adequate hematological, hepatic and renal function (renal function considered adequate as per protocol definitions - Effective/highly effective contraception for both male and female subjects as per definition for Part A and Part B, if the risk of conception exists - Fresh Biopsy or Archival Tumor Tissue (as per protocol definition for Part A and Part B) - Estimated life expectancy of more than 12 weeks Exclusion Criteria: - Participation in another clinical trial within the past 30 days - Concurrent treatment with a non permitted drug - Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co-regulatory targets such as 4-1BB - Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent - Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the subject has not fully recovered from the surgery within 4 weeks - Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-related adverse events [irAE]) while on study is allowed. Note: Subjects receiving bisphosphonate are eligible provided treatment was initiated at least 14 days before the first dose of avelumab - Subjects with active central nervous system (CNS) metastases are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy - Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ - Prior organ transplantation, including allogeneic stem-cell transplantation - Part A: Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti- HCV antibody screening test positive). - Active or history of any autoimmune disease (except for subjects with vitiligo) or immunodeficiencies that required treatment with systemic immunosuppressive drugs - Known severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to (>=) 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) - Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v 4.0; however, sensory neuropathy Grade <= 2 is acceptable 14. Pregnancy or lactation - Known alcohol or drug abuse - Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >= II), or serious cardiac arrhythmia requiring medication - All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment - Any psychiatric condition that would prohibit the understanding or rendering of informed consent - Legal incapacity or limited legal capacity - Non oncology vaccine therapies for prevention of infectious disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of trial drug administration. Vaccination while on trial is also prohibited except for administration of inactivated vaccines (for example, inactivated seasonal influenza vaccine)

Additional Information

Official title A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab (MSB0010718C) in Subjects With Merkel Cell Carcinoma
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by EMD Serono.