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

A Randomized Phase 3 Comparison of IMO-2125 With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)

A Phase 3 comparison of ipilimumab with and without IMO-2125 in advanced melanoma

Study Overview

• Status: Terminated
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: Ipilimumab; Drug: Tilsotolimod with Ipilimumab

Detailed Description

A Phase 3 global, multi-center, open-label comparison of ipilimumab with and without intratumoral IMO-2125 in subjects with advanced melanoma who had confirmed disease progression while on anti-PD-1

• Study Type: Interventional
• Enrollment (Actual): 481
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Greenslopes Private Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Center
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Queen Elizabeth Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • University Hospital Geelong
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Alberta Health Services Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hopsital
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc - Oncology clinic
  • Praha, Czechia, 100 34
    • Dermatovenerologika Klinika
  • Praha, Czechia, 10034
    • Vseobecna fakultni nemocnice v Praze
• France
  • Amiens, France, 80054
    • CHU Amiens Picardie - Hopital Sud
  • Dijon, France, 21000
    • CHU Dijon - Hopital Mitterrand
  • La Tronche, France, 38700
    • Chu de Grenoble
  • Lille, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Lyon Cedex 08, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13385
    • CHU de Marseille - Hôpital de la Timone
  • Paris, France, 75010
    • Hopital Saint Louis
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76031
    • CHU Hôpitaux de Rouen
  • Villejuif, France, 94805
    • Institut Gustave Roussy
  • Cedex
    • Clermont-Ferrand, Cedex, France, 63003
      • CHU - Clermont Ferrand
    • Rouen, Cedex, France, 25030
      • CHRU Besançon - Jean Minjoz
• Germany
  • Augsburg, Germany, 86179
    • Klinikum Augsburg
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin
  • Buxtehude, Germany, 21614
    • Elbe Kliniken
  • Hannöver, Germany, 30625
    • Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg Universitaets-Hautklinik
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Tübingen, Germany, 72076
    • Universitat Tubingen
  • Würzburg, Germany, 97080
    • Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universität Würzburg
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedale Policlinico di Bari
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia
  • Genova, Italy, 16132
    • IRCCS Azienda Ospedaliera Universitaria San Martino IST
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
  • Modena, Italy, 41124
    • Azienda Ospedaliero-Universitaria di Modena
  • Napoli, Italy, 80131
    • Istituto Nazionale di Tumori IRCCS "Fondazione Sen. G. Pascale"
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto-I.R.C.C.S.
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
  • Siena, Italy, 53100
    • Azienda Ospedaliero Universitaria Senese
  • Torino, Italy, 10126
    • Università di Torino
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Utrecht, Netherlands, 3584CX
    • Universitair Medisch Centrum Utrecht
• Spain
  • A Coruña, Spain, 15006
    • Hospital Universitario A Coruña
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebrón
  • Barcelona, Spain, 08036
    • Hospital Clínic Barcelona
  • Barcelona, Spain, 08028
    • Hospital Universitari Quiron Dexeus Barcelona
  • Donostia, Spain, 20014
    • Onkologikoa
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46014
    • Consorci Hospital General Universitari de València
• Sweden
  • Lund, Sweden, 221 85
    • Skånes Universitetssjukhus i Lund
  • Solna, Sweden, 17164
    • Karolinska Universitetssjukhuset
  • Växjö, Sweden, 351 85
    • Centrallasarettet i Växjö
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (UAB)
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner Md Anderson Cancer Center
    • Scottsdale, Arizona, United States, 85338
      • Cancer Treatment Centers of America (CTCA) - Western Regional Medical Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles (UCLA)
    • Sacramento, California, United States, 95816
      • Sutter Health Sacramento
    • San Diego, California, United States, 92093
      • University of California, San Diego (UCSD) - Moores Cancer Center
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center of Florida, Inc.
    • Orlando, Florida, United States, 32806
      • University of Florida Health Cancer Center - Orlando Health
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Health
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Health Care Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must be willing and able to sign the informed consent and comply with the study protocol.
2. Subjects must be ≥18 years of age.
3. 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.

4. 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:

   1. 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).
   2. 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.
   3. If BRAF mutation status is unknown, before randomization the subject must have BRAF testing performed using an approved assay method.
   4. 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.
5. Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.

6. Patients must meet the following laboratory criteria:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/mm3)
   2. Platelet count ≥ 75 x 10^9/L (75,000/mm3)
   3. Hemoglobin ≥ 8.0 g/dL (4.96 mmol/L)
   4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/minute
   5. Aspartate aminotransferase (AST) ≤ 2.5 x ULN; alanine aminotransferase (ALT) ≤ 2.5 x ULN; AST/ALT < 5 x ULN if liver involvement
   6. Serum bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert's Syndrome who must have a total bilirubin < 3 mg/dL
7. 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.
8. WOCBP must have a negative pregnancy test (serum or urine).

Exclusion Criteria:

1. Ocular melanoma.
2. Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.
3. Prior ipilimumab treatment with the exception of adjuvant treatment completed ≥6 months prior to enrollment
4. Systemic treatment with interferon (IFN)-α 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 requiring systemic steroid therapy receiving >10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study.
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. Active hepatitis A, B, or C infection.
11. Known diagnosis of human immunodeficiency virus (HIV) infection.
12. Women who are pregnant or breastfeeding.
13. Prior severe reaction to treatment with a human antibody 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A: ipilimumab; ipilimumab 3 mg/kg intravenous	Drug: Ipilimumab; Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.; Other Names: Yervoy®
EXPERIMENTAL: Arm B: IMO-2125 plus ipilimumab; IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous	Drug: Tilsotolimod with Ipilimumab; IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod; Other Names: IMO-2125 with Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1	The ORR for evaluable participants was calculated using the participant's best overall response (BOR). Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target lesions as assessed by MRI, CT or X-ray: Complete Response (CR) - disappearance of all target lesions; Partial Response (PR) - >=30% decrease from baseline of the sum of diameters of all target lesions; Stable Disease (SD) - does not qualify for CR, PR or Progression; Progressive Disease (PD) - 20% increase in the sum of diameters of target lesions. The calculation is derived from measuring the diameter (mm) of the target lesion at baseline and comparing target lesion diameter (mm) at intervals during treatment and/or post-treatment. Based on the percent of tumor decrease or increase, the appropriate category is assigned.	Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).
Summary of Overall Survival	Efficacy measured by overall survival (OS) was defined as the number of participants alive compared to the number of participants that died by treatment group.	OS is measured from the date of randomization to the date of death from any cause (up to 36 months).

Collaborators and Investigators

• Sponsor: Idera Pharmaceuticals, Inc.
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• for more information

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 30, 2018
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (ACTUAL): February 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; Melanoma; PD-1; metastatic; refractory; PD1; CTLA-4; skin cancer; TLR9 agonist; CTLA4; advanced melanoma; IMO-2125; illuminate 301; ILLUMINATE-301
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: 2125-MEL-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No