Clinical Trial 17938

Cancer Type: Cutaneous
Interventions:MSB00100718C (Avelumab); Not Applicable

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Andrew Brohl

Overview

Study Title

A Phase II, Open-label, Multicenter Trial to Investigate the Clinical Activity and Safety of MSB0010718C in Subjects with Merkel Cell Carcinoma

Summary

The purpose of this study is to evaluate the efficacy and safety of avelumab in participants with metastatic Merkel cell carcinoma (MCC) who must have received one line of chemotherapy for the treatment of metastatic MCC.

Objective

Primary Objective: The primary objective of the trial is to assess the clinical activity of MSB0010718C as determined by the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by an Independent Endpoint Review Committee (IERC) in subjects with metastatic Merkel cells carcinoma after failing first-line chemotherapy. Secondary Objectives: Secondary objectives are as follows: To assess the duration of response according to RECIST 1.1 To assess the progression-free survival time (PFS) according to RECIST 1.1 To assess the safety profile of MSB0010718C in subjects with MCC To assess the overall survival (OS) time To assess response status according to RECIST 1.1 at 6 and 12 months after start of study treatment To characterize the population PK of MSB0010718C in subjects with MCC by sparse sampling To evaluate the immunogenicity of MSB0010718C and to correlate it to exposure Exploratory Objectives: Exploratory objectives are as follows: To correlate the immunogenicity of MSB0010718C with clinical results (ORR and adverse events [AEs]) To assess the immune-related best overall response (irBOR) and immune-related PFS (irPFS) using the modified immune-related response criteria (irRC), derived from RECIST 1.1 To compare time to progression (TTP) on last prior anticancer therapy to PFS time on treatment with MSB0010718C. To evaluate changes in biomarkers in relation to disease responses to MSB0010718C. To evaluate the association between tumor programmed death ligand 1 (PD-L1) expression and best overall response (BOR) To explore the benefits of SB0010718C as perceived by subjects with metastatic MCC.

Inclusion Criteria

  • Signed written informed consent
  • Age 18 years and above
  • Histologically proven Merkel cell carcinoma (MCC) as defined in the protocol
  • For Part A - Progressive disease after receiving 1 line of chemotherapy for metastatic MCC
  • For Part B - Participants 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 to1
  • Disease must be measurable with at least 1 uni-dimensional measurable lesion by Response Evaluation Criteria in Solid Tumors (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 as defined in the protocol. 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 participant 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 steroids (that is, for allergic reactions or the management of immune-related adverse events [irAE]) is allowed while on study. Note: Participants receiving bisphosphonate are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
  • Active central nervous system (CNS) metastases. Potential participants 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 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 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 Version 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 Version 4.0; however, sensory neuropathy Grade less than or equal to (> Pregnancy or lactation
  • Known alcohol or drug abuse
  • Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident or stroke (less than [=II), or serious cardiac arrhythmia requiring medication
  • All other significant diseases which, in the opinion of the Investigator, might impair 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 within 4 weeks of trial drug administration. Vaccination while on trial is also prohibited except for administration of the inactivated influenza vaccine.