A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma
Metastatic Melanoma

About this trial
This is an interventional treatment trial for Metastatic Melanoma focused on measuring Melanoma, PD1, PD-1, refractory, metastatic, IMO-2125, illuminate 301, TLR9 agonist, advanced melanoma, CTLA4, CTLA-4, immunotherapy, skin cancer, ILLUMINATE-301
Eligibility Criteria
Inclusion Criteria:
- Subjects must be willing and able to sign the informed consent and comply with the study protocol.
- Subjects must be ≥18 years of age.
- Subjects must have 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.
Patients must have confirmed progression during or after treatment with a PD-1 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 it is accompanied by correlative symptoms.
In addition, all the following must hold:
- 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).
- 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.
- If BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
- Patients with BRAF-positive tumor(s) are eligible for the study if they received prior treatment with a BRAF inhibitor (alone of in combination with a MEK inhibitor) or declined targeted therapy.
- Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
Patients must meet the following laboratory criteria:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/mm3)
- Platelet count ≥ 75 x 10^9/L (75,000/mm3)
- Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/minute
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN; AST/ALT < 5 x ULN if liver involvement
- Serum bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert's Syndrome who must have a total bilirubin < 3 mg/dL
- Women of childbearing potential (WOCBP) and men must agree to use effective contraceptive methods from Screening throughout the study treatment period and until at least 90 days after the last dose of either ipilimumab or IMO-2125, whichever is later.
- WOCBP must have a negative pregnancy test (serum or urine).
Exclusion Criteria:
- Ocular melanoma.
- Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.
- Prior ipilimumab treatment with the exception of adjuvant treatment completed ≥6 months prior to enrollment
- Systemic treatment with interferon (IFN)-α within the previous 6 months.
- Known hypersensitivity to any oligodeoxynucleotide.
- Active autoimmune disease requiring disease-modifying therapy at the time of Screening.
- Subjects requiring systemic steroid therapy receiving >10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study.
- 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).
- Active systemic infections requiring antibiotics
- Active hepatitis A, B, or C infection.
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Women who are pregnant or breastfeeding.
- Prior severe reaction to treatment with a human antibody that cannot be managed with standard supportive measures.
- 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
- Impaired cardiac function or clinically significant cardiac disease.
Sites / Locations
- University of Alabama at Birmingham (UAB)
- Banner MD Anderson Cancer Center
- Cancer Treatment Centers of America (CTCA) - Western Regional Medical Center
- University of Southern California
- University of California, Los Angeles (UCLA)
- Sutter Health Sacramento
- University of California, San Diego (UCSD) - Moores Cancer Center
- Stanford Cancer Center
- Mount Sinai Medical Center of Florida, Inc.
- University of Florida Health Cancer Center - Orlando Health
- The Valley Hospital
- University of Cincinnati Health
- The Cleveland Clinic Foundation
- The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
- MD Anderson Cancer Center
- Inova Health Care Services
- Greenslopes Private Hospital
- Icon Cancer Center
- Gold Coast University Hospital
- Queen Elizabeth Hospital
- University Hospital Geelong
- Fiona Stanley Hospital
- Tom Baker Cancer Centre
- Alberta Health Services Cross Cancer Institute
- Princess Margaret Hopsital
- Fakultni nemocnice Olomouc - Oncology clinic
- Dermatovenerologika Klinika
- Vseobecna fakultni nemocnice v Praze
- CHU - Clermont Ferrand
- CHRU Besançon - Jean Minjoz
- CHU Amiens Picardie - Hopital Sud
- CHU Dijon - Hôpital Mitterrand
- CHU de Grenoble
- CHRU de Lille - Hôpital Claude Huriez
- Centre Leon Berard
- CHU de Marseille - Hopital de la Timone
- Hopital Saint Louis
- Centre Hospitalier Lyon Sud
- CHU Hopitaux de Rouen
- Institut Gustave Roussy
- Klinikum Augsburg
- Charite Universitaetsmedizin Berlin
- Elbe Kliniken
- Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie
- Universitaetsklinikum Heidelberg Universitaets-Hautklinik
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
- Universitatsklinikum Regensburg
- Universität Tübingen
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universität Würzburg
- Azienda Ospedale Policlinico di Bari
- Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
- ASST degli Spedali Civili di Brescia
- IRCCS Azienda Ospedaliera Universitaria San Martino IST
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
- Istituto Europeo di Oncologia
- Azienda Ospedaliero-Universitaria di Modena
- Istituto Nazionale di Tumori IRCCS "Fondazione Sen. G. Pascale"
- Istituto Oncologico Veneto-I.R.C.C.S.
- Azienda Ospedaliero Universitaria Pisana
- Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
- Azienda Ospedaliero Universitaria Senese
- Universita di Torino
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Utrecht
- Hospital Universitario A Coruna
- Hospital Germans Trias i Pujol
- Hospital Universitari Quiron Dexeus Barcelona
- Hospital Universitario Vall d'Hebron
- Hospital Clinic Barcelona
- Onkologikoa
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario Ramon y Cajal
- Hospital Universitario Virgen Macarena
- Consorci Hospital General Universitari de Valencia
- Skånes Universitetssjukhus i Lund
- Karolinska Universitetssjukhuset
- Centrallasarettet i Växjö
- Bristol Haematology and Oncology Centre
- Guy's Hospital
- Royal Marsden Foundation Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A: ipilimumab
Arm B: IMO-2125 plus ipilimumab
ipilimumab 3 mg/kg intravenous
IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous