Refractory melanoma is a malignant tumor of melanocytes which originates predominantly from skin. MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
Idera Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be willing and able to sign the informed consent and comply with the study protocol. 2. Must be =18 years of age. 3. Histologically confirmed metastatic melanoma with measurable (by RECIST v1.1), stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease that is accessible for injection. Stage should be determined using the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Seventh Edition. 4. Confirmed progression during or after treatment with a PD-inhibitor (cannot be part of a bi-specific antibody), e.g.,nivolumab or pembrolizumab. Confirmed progression is defined as: • Radiological progression (confirmed at least 4 weeks after the initial scan showing PD); or • For progression based solely on worsening of non-target or new, non-measurable disease, confirmation by an additional scan at least 4 weeks after the initial scan unless progression is accompanied by correlative symptoms. In addition, all the following must hold: a) No intervening anti-cancer therapy between the last course of PD-1 inhibitor treatment and the first dose of study treatment is allowed except for local measures (e.g., surgical excision or biopsy, focal radiation therapy). b) The interval between last PD-1 inhibitor and start of study treatment should be at least 21 days with no residual anti-PD-1-related immune toxicities in excess of Grade 1 severity. c) Subjects who had adjuvant anti-PD-1 treatment are eligible if they have either disease recurrence after the end of adjuvant treatment or on-treatment disease recurrence after =12 weeks of adjuvant treatment. d) If subject BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method. e) Patients with BRAF-positive tumor(s) are eligible for the study if they received prior treatment with a BRAF inhibitor (alone or in combination with a MEK inhibitor) or declined targeted therapy. 5. ECOG Performance Status =1. 6. Adequate baseline organ function as defined by: a) Absolute neutrophil count (ANC) =1.5 x 109/L (1500/mm3) b) Platelet count =75 x 109/L (75,000/mm3) c) Hemoglobin =8.0 g/dL (4.96 mmol/L) d) Serum creatinine =1.5 x upper limit of normal (ULN) or calculated creatinine clearance =60 mL/minute (=Grade 1) e) Aspartate aminotransferase (AST) =2.5 x ULN; alanine aminotransferase (ALT) =2.5 x ULN; AST/ALT =65 years) yes F.1.3.1 Number of subjects for this age range 248
Exclusion criteria
Exclusion criteria: 1. Ocular melanoma. 2. Prior therapy with a TLR agonist, excluding topical agents. 3. Prior ipilimumab with the exception of adjuvant treatment completed =6 months prior to enrollment. 4. Systemic treatment with IFN-a within the previous 6 months. 5. Known hypersensitivity to any oligodeoxynucleotide. 6. Active autoimmune disease requiring disease modifying therapy at the time of screening. 7. Subjects with a requirement for systemic steroids should be receiving >10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study treatment. 8. Subjects with another primary malignancy that has not been in remission for at least 3 years with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer with non-detectable prostate-specific antigen, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou (Pap) smear, and thyroid cancer (except anaplastic). 9. Active systemic infections requiring antibiotics. 10. Known active, hepatitis A, B, or C infection. 11. Known diagnosis of human immunodeficiency virus (HIV) infection. 12. Women who are pregnant or breast-feeding. 13. Prior anaphylactic or other severe infusion reaction associated with human antibody administration that cannot be managed with standard supportive measures. 14. Presence of known central nervous system, meningeal, or epidural metastatic disease. However, subjects with known brain metastases are allowed if the brain metastases are stable for =4 weeks before the first dose of study treatment. Stable is defined as neurological symptoms not present or resolved to baseline, no radiologic evidence of progression, and steroid requirement of prednisone =10 mg/day or equivalent. 15. Impaired cardiac function or clinically significant cardiac disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the efficacy measured by overall survival [OS] of intratumoral IMO-2125 in combination with ipilimumab versus ipilimumab alone.;Secondary Objective: Assess other measures of clinical benefit, safety, pharmacokinetics (PK), and patient-reported outcomes (PROs). Investigate potential biomarkers and the incidence of anti-IMO-2125 and anti-ipilimumab antibodies.;Primary end point(s): The primary endpoint family (see FDA Guidance for Industry, 2017) includes: • OS, defined as the time to death from any cause measured from the date of randomization. ;Timepoint(s) of evaluation of this end point: Tumor assessments will be performed at Screening and Week 12, then every 8 weeks for the first year and every 12 weeks during subsequent years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR by investigator assessment using RECIST v1.1 •Duration of response (DoR) by blinded independent review and by investigator assessment using RECIST v1.1, measured from the time that criteria are first met for CR or partial response (PR)(whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented • Durable response rate (DRR) by blinded independent review and investigator assessment using RECIST v1.1, defined as the rate of CR or PR lasting =6 months with onset during the first 12 months of treatment • Time to response (TTR), defined as time to a complete or partial response (using RECIST v1.1 ) measured from the date of randomization, by blinded independent review and investigator assessment • Progression-free survival (PFS), defined as the time to disease progression or death from any cause measured from the date of randomization, by blinded independent review and investigator assessment (using RECIST v1.1) • Landmark PFS at 1 and 2 years by blinded independent review and investigator assessment (using RECIST v1.1) and landmark OS at 1 and 2 years • PRO using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) • Safety, including AEs, laboratory and vital sign tests, electrocardiograms (ECGs), ECOG, and physical examination • Plasma PK of IMO 2125 ;Timepoint(s) of evaluation of this end point: Various, refer to information in E.5.2. | — |
Countries
Australia, Canada, Czech Republic, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactJennessa Martin
Idera Pharmaceuticals, Inc.
Outcome results
None listed