Advanced Melanoma Advanced skincancer
Conditions
Interventions
Group A: Study subjects will be administered 3mg/kg ipilimumab 4 times
intravenously (in week 1, 4, 7 and 10).
Group B: Study subjects will be administered 3mg/kg ipilimumab 4 times
intravenously (
Sponsors
Idera Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 99 Years
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 Response Evaluation Criteria in Solid Tumors [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 either nivolumab or pembrolizumab. Confirmed progression is defined as: * Radiological progression (confirmed at least 4 weeks after the initial scan showing progressive disease); 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 it is accompanied by correlative symptoms. In addition, all the following must hold: a) No intervening anti-cancer therapy between the last course of nivolumab or pembrolizumab 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 nivolumab or pembrolizumab and start of study treatment should be at least 21 days with no residual anti-PD-1-related immunie toxicities in excess of Grade 1 severity. c) Prior BRAF inhibitor treatment (alone or in combination with a MEK inhibitor) is required if the tumor carries a BRAF V600E or V600K mutation. 5. Eastern Cooperative Oncology Group (ECOG) Peformance 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 *100 x 109/L (100,000/mm3) c) Hemoglobin *8.0 g/dL (4.96 mmol/L) d) Serum creatinine *1.5 x upper limit of normal (ULN) or 24-hour creatinine clearance *60 mL/minute (*Grade 1) e) Aspartate aminotransferase (AST) *2.5 x ULN; alanine aminotransferase (ALT) *2.5 x ULN; AST/ALT <5 x ULN if liver involvement (*Grade 1) f) Serum bilirubin *1.5 x ULN, except in subjects with Gilbert*s Syndrome who must have a total bilirubin <3 mg/dL (*Grade 1) 7. Women of childbearing potential (WOCBP) and men must agree to use effective contraceptive methods from screening until at least 3 months after the last dose of ipilimumab (Arm A) and at least 4 weeks after the last dose of IMO-2125 (Arm B). Non-childbearing potential is defined as a woman who meets either of the following criteria: a) postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy. Effective contraception methods are defined as one of the following: a) True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. b) Condoms and spermicide c) Diaphragm and spermicide d) Oral or implanted hormonal contraceptive (e.g., Implanon*) NOTE: For subjects in Sweden, low dose oral contraceptives
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-* 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 receiving more than physiologic doses of systemic steroids (>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 |
|---|---|
| Primary Endpoint Family The primary endpoint family (see Food and Drug Administration [FDA] Guidance for Industry, 2017) includes: * ORR by blinded independent review using RECIST v1.1 * OS, defined as the time to death from any cause measured from the date of randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| * 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 blindend 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 | — |
Countries
Netherlands
Outcome results
None listed