Clinical Trial 18975

Cancer Type: Cutaneous
Interventions:REGN2810

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

  • Zeynep Eroglu

Overview

Study Title

A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1, in Patients with Advanced Basal Cell Carcinoma who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy

Summary

This study is being done to test effects of REGN2810 (''study drug") in people with advanced basal cell carcinoma (BCC). These effects could be good (for example, shrinking of tumors) or bad (called side effects). Researchers will study the effects and how long they last to understand if REGN2810 could be used for treatment of advanced basal cell carcinoma (BCC).

Objective

The Primary Objective of the study is to estimate the overall response rate (ORR) for metastatic basal cell carcinoma (BCC) (Group 1) or unresectable locally advanced BCC (Group 2), according to central review, when treated with REGN2810 monotherapy in patients who have progressed on Hedgehog Pathway Inhibitor (HHI) therapy, or were intolerant of prior HHI therapy. The Secondary Objectives for both Group 1 and Group 2 are to: - Estimate ORR according to investigator review; - Estimate the duration of response, progression-free survival (PFS) by central and investigator review, and overall survival (OS); - Estimate the complete response (CR) rate by central review; - Assess the safety and tolerability of REGN2810; - Assess the pharmacokinetics (PK) of REGN2810 (at select sites only); - Assess the immunogenicity of REGN2810; - Assess the impact of REGN2810 on quality of life using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and Skindex-16. The Exploratory Objectives (for Group 2 only) are to explore the pharmacodynamic effects of REGN2810 in tumor biopsies obtained at baseline, during treatment, and at progression in BCC patients treated with REGN2810, and to assess predictive potential and correlation to clinical response for biomarkers of interest including but not limited to: - Tumor RNA expression; - Number and distribution of tumor-infiltrating lymphocytes (TILs) (CD8+ T cells, CD4+ T cells, T regulatory cells, and tissue permitting, other subtypes such as B cells, myeloid-derived cells, natural killer [NK] cells, etc.); - Expression levels (mRNA and/or protein) of programmed death ligand 1(PD-L1), glucocorticoid-induced TNFR family related gene(GITR), and lymphocyte activation gene-3 (LAG-3), and possibly other check-point modulators; - Mutations in known oncogenes and potential tumor neoantigens; - Tumor mutational burden.

Inclusion Criteria

  • Confirmed diagnosis of invasive Basal Cell Carcinoma (BCC)
  • Progression of disease on hedgehog inhibitor (HHI) therapy or intolerance of prior HHI therapy
  • At least 1 measurable lesion
  • ≥18 years of age
  • Hepatic function, renal function, bone marrow function in defined lab-value-ranges
  • Anticipated life expectancy >12 weeks
  • Consent to provide archived tumor biopsy material (all patients)
  • Group 2: consent to undergo research biopsies
  • Group 2: must not be a candidate for radiation therapy or surgery
  • Comply with study procedures and site visits
  • Sign Subject Information Sheet and Informed Consent Form
  • Note: Other protocol-defined inclusion criteria apply

  • Exclusion Criteria

  • Ongoing or recent significant autoimmune disease
  • Prior treatment with specific pathway-blockers (PD-1/PD-L1)
  • Prior treatment with immune-modulating agents within 28 days before REGN2810
  • Untreated brain metastasis that may be considered active
  • Immunosuppressive corticosteroid doses (>10mg prednisone) within 28 days prior to treatment with REGN2810
  • Active infections requiring therapy, including HIV, hepatitis
  • Pneumonitis within the last 5 years
  • Cancer treatment other than radiation therapy, including investigational or standard of care, within 30 > days prior to treatment with REGN2810
  • Documented allergic reactions or similar to antibody treatments
  • Concurrent malignancies other than BCC, other than those with negligible risk of metastases or death
  • Any acute or chronic psychiatric problems
  • Having received a solid organ transplantation
  • Inability to undergo contrast radiological assessments
  • Breastfeeding, pregnant, women of childbearing potential not using contraception
  • Note: Other protocol-defined inclusion/exclusion criteria apply