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

NCT03445533 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 2125-MEL-301
• Study Type: interventional
• Target: 481
• Locations: 11 countries
• Sites: 80

Brief Summary

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

Conditions

Metastatic Melanoma

Keywords

Melanoma; PD1; PD-1; refractory; metastatic; IMO-2125; illuminate 301; TLR9 agonist; advanced melanoma; CTLA4; CTLA-4; immunotherapy; skin cancer; ILLUMINATE-301

Outcome Measures

Primary Outcomes (2)

• 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).

Study Arms (2)

Arm A: ipilimumab

EXPERIMENTAL

ipilimumab 3 mg/kg intravenous

Drug: Ipilimumab

Arm B: IMO-2125 plus ipilimumab

EXPERIMENTAL

IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous

Drug: Tilsotolimod with Ipilimumab

Interventions

Ipilimumab DRUG

Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.

Also known as: Yervoy®

Arm A: ipilimumab

Tilsotolimod with Ipilimumab DRUG

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

Also known as: IMO-2125 with Yervoy

Arm B: IMO-2125 plus ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idera Pharmaceuticals, Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (80)

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35294, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Cancer Treatment Centers of America (CTCA) - Western Regional Medical Center

Scottsdale, Arizona, 85338, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Sutter Health Sacramento

Sacramento, California, 95816, United States

Location

University of California, San Diego (UCSD) - Moores Cancer Center

San Diego, California, 92093, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Mount Sinai Medical Center of Florida, Inc.

Miami Beach, Florida, 33140, United States

Location

University of Florida Health Cancer Center - Orlando Health

Orlando, Florida, 32806, United States

Location

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

University of Cincinnati Health

Cincinnati, Ohio, 45219, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)

Columbus, Ohio, 43221, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Health Care Services

Falls Church, Virginia, 22042, United States

Location

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

Location

Icon Cancer Center

South Brisbane, Queensland, 4101, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

University Hospital Geelong

Geelong, Victoria, 3220, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Alberta Health Services Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Hopsital

Toronto, Ontario, M5G 2M9, Canada

Location

Fakultni nemocnice Olomouc - Oncology clinic

Olomouc, 779 00, Czechia

Location

Dermatovenerologika Klinika

Prague, 100 34, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 10034, Czechia

Location

CHU - Clermont Ferrand

Clermont-Ferrand, Cedex, 63003, France

Location

CHRU Besançon - Jean Minjoz

Rouen, Cedex, 25030, France

Location

CHU Amiens Picardie - Hopital Sud

Amiens, 80054, France

Location

CHU Dijon - Hôpital Mitterrand

Dijon, 21000, France

Location

CHU de Grenoble

La Tronche, 38700, France

Location

CHRU de Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

CHU de Marseille - Hopital de la Timone

Marseille, 13385, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU Hopitaux de Rouen

Rouen, 76031, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Klinikum Augsburg

Augsburg, 86179, Germany

Location

Charite Universitaetsmedizin Berlin

Berlin, 10117, Germany

Location

Elbe Kliniken

Buxtehude, 21614, Germany

Location

Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie

Hannover, 30625, Germany

Location

Universitaetsklinikum Heidelberg Universitaets-Hautklinik

Heidelberg, 69120, Germany

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, 55131, Germany

Location

Universitatsklinikum Regensburg

Regensburg, 93053, Germany

Location

Universität Tübingen

Tübingen, 72076, Germany

Location

Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universität Würzburg

Würzburg, 97080, Germany

Location

Azienda Ospedale Policlinico di Bari

Bari, 70124, Italy

Location

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, 70124, Italy

Location

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino IST

Genova, 16132, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliero-Universitaria di Modena

Modena, 41124, Italy

Location

Istituto Nazionale di Tumori IRCCS "Fondazione Sen. G. Pascale"

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto-I.R.C.C.S.

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

Azienda Ospedaliero Universitaria Senese

Siena, 53100, Italy

Location

Universita di Torino

Torino, 10126, Italy

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584CX, Netherlands

Location

Hospital Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, 08028, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Onkologikoa

Donostia / San Sebastian, 20014, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Consorci Hospital General Universitari de Valencia

Valencia, 46014, Spain

Location

Skånes Universitetssjukhus i Lund

Lund, 221 85, Sweden

Location

Karolinska Universitetssjukhuset

Solna, 17164, Sweden

Location

Centrallasarettet i Växjö

Vaxjo, 351 85, Sweden

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Royal Marsden Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Diab A, Ascierto PA, Maio M, Abdel-Wahab R, Negrier S, Mortier L, Arenberger P, Dalle S, Krajsova I, de la Cruz L, Leccia MT, Guida M, Lebbe C, Grob JJ, Butler MO, In GK, Loquai C, Walker JWT, Atkinson V, Kapiteijn E, Haferkamp S, Chunduru S, Rahimian S, Guidoboni M, Robert C. Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301). J Clin Oncol. 2025 May 20;43(15):1800-1809. doi: 10.1200/JCO.24.00727. Epub 2025 Mar 6.

  PMID: 40048691 DERIVED

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis; Diabetes Mellitus, Insulin-Dependent, 12; Skin Neoplasms

Interventions

Ipilimumab; tilsotolimod

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Idera Pharmaceuticals, Inc.

lcolfer@iderapharma.com

484-348-1605

Study Officials

• Idera Medical Director

  Idera Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: February 26, 2018
• Study Start: May 30, 2018
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); AU (6); FR (12); DE (9); CZ (3); IT (13); NL (2); US (16); ES (10); SE (3); GB (3)