melanoma unresectable melanoma
Conditions
Interventions
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of stage III (unresectable) or stage IV cutaneous (non-acral lentiginous) with at least 1 lesion that is measurable by RECIST 1.1 criteria and accessible for biopsies. , 2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (ECOG PS 1 definition: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work)., 3. *18 years old, 4. Hepatic function:, a. Total bilirubin *1.5 x upper limit of normal, b. Transaminases *3 x ULN, c. Alkaline phosphatase (ALP) *2.5 x ULN, 5. Serum creatinine *1.5 x ULN or estimated glomerular filtration rate >50 mL/min/1.73m^2, 6. Bone marrow function:, a. Hemoglobin *9.0 g/dL, b. Absolute neutrophil count (ANC) *1.5 x 10^9/L, c. Platelet count *75 x 10^9/L, 7. Willing and able to comply with clinic visits and study-related procedures, 8. Provide signed informed consent, 9. Able to understand and complete study-related questionnaires, 10. Anticipated life expectancy >12 weeks
Exclusion criteria
Exclusion criteria: 1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs., 2. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway., 3. Prior treatment with other immune modulating anti-cancer agents., 4. Untreated or active brain metastases or spinal cord compression. , 5. Immunosuppressive corticosteroid doses, 6. History of human immunodeficiency virus (HIV)., 7. Uncontrolled chronic hepatitis B or C., 8. History of pneumonitis within the last 5 years., 9. Grade 3 or 4 hypercalcemia at time of enrollment., 10. Any systematic anticancer treatment, investigational or standard of care, within 30 days of the initial administration of REGN2810 or planned to occur during the study period (Patients receiving bisphosphonates or denosumab are not excluded)., 11. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments., 12. Known allergy to doxycycline or tetracycline, 13. Concurrent malignancy other than melanoma and/or history of malignancy other than melanoma within 3 years of date of first planned dose of REGN2810, except for tumors with negligible risk of metastasis or death, such as adequately treated basal cell carcinoma (BCC) of the skin, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast, or history of prostate adenocarcinoma treated with curative intent at least 3 years prior and with undetectable PSA for at least 3 years prior to enrollment. Patients with hematologic malignancies (e.g., chronic lymphocytic leukemia, CLL) are excluded., 14. Any acute or chronic psychiatric problems that, in the opinion of the investigator, make the patient ineligible for participation., 15. Patients with a history of solid organ transplant., 16. Any medical co-morbidity, clinical laboratory finding, or concomitant medication that, in the opinion of the investigator, renders the patient an unsuitable candidate for tumor biopsies due to high safety risks., 17. Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation in a clinical trial due to high safety risks and/or potential to affect interpretation of results of the study., 18. Inability to undergo any response assessment by contrast-enhanced radiologic imaging., 19. Pregnant or breastfeeding women, 20. Sexually active men or women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose, during the study, and for at least 6 months after the last dose. , 21. Prior treatment with idelalisib, 22. Radiation therapy within 2 weeks prior to enrollment and not recovered to baseline from any AE due to radiation., See protocol section 6.2.2. for more detailed information
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The correlation between changes in the tumor microenvironment and the change in tumor volume following REGN2810 treatment versus baseline. The changes in tumor microenvironment that will be correlated to the change in tumor volume may include: * Changes in number of immune cells in the tumor microenvironment: o Changes in the number of tumor infiltrating lymphocytes (TILs) focusing on CD8+ T cells, CD4+ T cells, Tregs and myeloid cells o Changes in cell type representation in the immune cell infiltrate (normalized against total number of TILs) * Fold-change in tumor gene expression focusing on the top 10 genes differentially affected in responders compared to non-responders (changes in expression of additional genes of interest may be evaluated as part of the exploratory analyses) * Changes in positive and negative immune checkpoint modulator expression focusing on LAG3, TIM3, and GITR (other molecules of interest may be evaluated as part of the exploratory analyses): o Changes in overall expression level (assessed by RNASeq) and in situ expression (assessed by RNAScope) * Changes in number of cells expressing molecule of interest. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Correlation between baseline tumor characteristics and the change in tumor volume following treatment in REGN2810. o Tumor gene expression as assessed by tumor RNASeq o Tumor mutational load as assessed by whole-exome DNA sequencing and comparison between somatic and germline DNA * Adverse Event (AEs) in patients treated with REGN2810. * Concentrations of REGN2810 in serum and anti-REGN2810 antibody levels * The overall response rate (ORR) and progression-free survival (PFS) in patients treated with REGN2810. | — |
Countries
Korea (the Republic of), Netherlands, Serbia, United Kingdom
Outcome results
None listed