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

NCT ID: NCT03445533

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 481 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-30
• Study Completion Date: 2021-06-01

Brief Summary

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

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

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: ipilimumab

ipilimumab 3 mg/kg intravenous

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

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

Arm B: IMO-2125 plus ipilimumab

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

Group Type: EXPERIMENTAL

Tilsotolimod with Ipilimumab

Intervention Type: 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

Interventions

Ipilimumab

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Yervoy®; IMO-2125 with Yervoy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Idera Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Idera Medical Director

Role: STUDY_DIRECTOR

Idera Pharmaceuticals, Inc.

Locations

University of Alabama at Birmingham (UAB)

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

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

Scottsdale, Arizona, United States

University of Southern California

Los Angeles, California, United States

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Sutter Health Sacramento

Sacramento, California, United States

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

San Diego, California, United States

Stanford Cancer Center

Stanford, California, United States

Mount Sinai Medical Center of Florida, Inc.

Miami Beach, Florida, United States

University of Florida Health Cancer Center - Orlando Health

Orlando, Florida, United States

The Valley Hospital

Ridgewood, New Jersey, United States

University of Cincinnati Health

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

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

Columbus, Ohio, United States

MD Anderson Cancer Center

Houston, Texas, United States

Inova Health Care Services

Falls Church, Virginia, United States

Greenslopes Private Hospital

Greenslopes, Queensland, Australia

Icon Cancer Center

South Brisbane, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

Queen Elizabeth Hospital

Woodville South, South Australia, Australia

University Hospital Geelong

Geelong, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Alberta Health Services Cross Cancer Institute

Edmonton, Alberta, Canada

Princess Margaret Hopsital

Toronto, Ontario, Canada

Fakultni nemocnice Olomouc - Oncology clinic

Olomouc, , Czechia

Dermatovenerologika Klinika

Prague, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

CHU - Clermont Ferrand

Clermont-Ferrand, Cedex, France

CHRU Besançon - Jean Minjoz

Rouen, Cedex, France

CHU Amiens Picardie - Hopital Sud

Amiens, , France

CHU Dijon - Hôpital Mitterrand

Dijon, , France

CHU de Grenoble

La Tronche, , France

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

Centre Leon Berard

Lyon, , France

CHU de Marseille - Hopital de la Timone

Marseille, , France

Hopital Saint Louis

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU Hopitaux de Rouen

Rouen, , France

Institut Gustave Roussy

Villejuif, , France

Klinikum Augsburg

Augsburg, , Germany

Charite Universitaetsmedizin Berlin

Berlin, , Germany

Elbe Kliniken

Buxtehude, , Germany

Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie

Hannover, , Germany

Universitaetsklinikum Heidelberg Universitaets-Hautklinik

Heidelberg, , Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, , Germany

Universitatsklinikum Regensburg

Regensburg, , Germany

Universität Tübingen

Tübingen, , Germany

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

Würzburg, , Germany

Azienda Ospedale Policlinico di Bari

Bari, , Italy

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, , Italy

ASST degli Spedali Civili di Brescia

Brescia, , Italy

IRCCS Azienda Ospedaliera Universitaria San Martino IST

Genova, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliero-Universitaria di Modena

Modena, , Italy

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

Napoli, , Italy

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

Padua, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

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

Rome, , Italy

Azienda Ospedaliero Universitaria Senese

Siena, , Italy

Universita di Torino

Torino, , Italy

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Hospital Universitario A Coruna

A Coruña, , Spain

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Clinic Barcelona

Barcelona, , Spain

Onkologikoa

Donostia / San Sebastian, , Spain

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Consorci Hospital General Universitari de Valencia

Valencia, , Spain

Skånes Universitetssjukhus i Lund

Lund, , Sweden

Karolinska Universitetssjukhuset

Solna, , Sweden

Centrallasarettet i Växjö

Vaxjo, , Sweden

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Guy's Hospital

London, , United Kingdom

Royal Marsden Foundation Trust

London, , United Kingdom

Countries

United States; Australia; Canada; Czechia; France; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40048691 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2125-MEL-301

Identifier Type: -

Identifier Source: org_study_id