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Metastatic MelanomaPhase 3NCT03445533

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

A Phase 3 study testing Ipilimumab and Tilsotolimod with Ipilimumab in people with Metastatic Melanoma, run by Idera Pharmaceuticals, Inc. at 80 sites in 11 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

A Phase 3 comparison of ipilimumab with and without IMO-2125 in advanced melanoma Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Ipilimumab and Tilsotolimod with Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
481 participants
Where
80 sitesin 11 countries
Study dates
30 May 2018to 1 Jun 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

80 sites in 11 countries.

80 sites in 11 countries

United States16 sites

  • University of Alabama at Birmingham (UAB)

    Birmingham, Alabama, 35294

  • University of Cincinnati Health

    Cincinnati, Ohio, 45219

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

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

    Columbus, Ohio, 43221

  • Inova Health Care Services

    Falls Church, Virginia, 22042

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Southern California

    Los Angeles, California, 90033

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Mount Sinai Medical Center of Florida, Inc.

    Miami Beach, Florida, 33140

  • University of Florida Health Cancer Center - Orlando Health

    Orlando, Florida, 32806

  • The Valley Hospital

    Ridgewood, New Jersey, 07450

  • Sutter Health Sacramento

    Sacramento, California, 95816

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

    San Diego, California, 92093

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

    Scottsdale, Arizona, 85338

  • Stanford Cancer Center

    Stanford, California, 94305

Other trials in United States

Italy13 sites

  • Azienda Ospedale Policlinico di Bari

    Bari, 70124

  • Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

    Bari, 70124

  • ASST degli Spedali Civili di Brescia

    Brescia, 25123

  • IRCCS Azienda Ospedaliera Universitaria San Martino IST

    Genova, 16132

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, 47014

  • Istituto Europeo di Oncologia

    Milan, 20141

  • Azienda Ospedaliero-Universitaria di Modena

    Modena, 41124

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

    Naples, 80131

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

    Padova, 35128

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126

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

    Rome, 00168

  • Azienda Ospedaliero Universitaria Senese

    Siena, 53100

  • Universita di Torino

    Torino, 10126

Other trials in Italy

France12 sites

  • CHU Amiens Picardie - Hopital Sud

    Amiens, 80054

  • CHU - Clermont Ferrand

    Clermont-Ferrand, Cedex, 63003

  • CHU Dijon - Hôpital Mitterrand

    Dijon, 21000

  • CHU de Grenoble

    La Tronche, 38700

  • CHRU de Lille - Hôpital Claude Huriez

    Lille, 59037

  • Centre Leon Berard

    Lyon, 69373

  • CHU de Marseille - Hopital de la Timone

    Marseille, 13385

  • Hopital Saint Louis

    Paris, 75010

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • CHRU Besançon - Jean Minjoz

    Rouen, Cedex, 25030

  • CHU Hopitaux de Rouen

    Rouen, 76031

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Spain10 sites

  • Hospital Universitario A Coruna

    A Coruña, 15006

  • Hospital Germans Trias i Pujol

    Badalona, 08916

  • Hospital Universitari Quiron Dexeus Barcelona

    Barcelona, 08028

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic Barcelona

    Barcelona, 08036

  • Onkologikoa

    Donostia / San Sebastian, 20014

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Consorci Hospital General Universitari de Valencia

    Valencia, 46014

Other trials in Spain

Germany9 sites

  • Klinikum Augsburg

    Augsburg, 86179

  • Charite Universitaetsmedizin Berlin

    Berlin, 10117

  • Elbe Kliniken

    Buxtehude, 21614

  • Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie

    Hannover, 30625

  • Universitaetsklinikum Heidelberg Universitaets-Hautklinik

    Heidelberg, 69120

  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

    Mainz, 55131

  • Universitatsklinikum Regensburg

    Regensburg, 93053

  • Universität Tübingen

    Tübingen, 72076

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

    Würzburg, 97080

Other trials in Germany

Australia6 sites

  • University Hospital Geelong

    Geelong, Victoria, 3220

  • Greenslopes Private Hospital

    Greenslopes, Queensland, 4120

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Icon Cancer Center

    South Brisbane, Queensland, 4101

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

Other trials in Australia

Canada3 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Alberta Health Services Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Princess Margaret Hopsital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Czechia3 sites

  • Fakultni nemocnice Olomouc - Oncology clinic

    Olomouc, 779 00

  • Dermatovenerologika Klinika

    Prague, 100 34

  • Vseobecna fakultni nemocnice v Praze

    Prague, 10034

Other trials in Czechia

Sweden3 sites

  • Skånes Universitetssjukhus i Lund

    Lund, 221 85

  • Karolinska Universitetssjukhuset

    Solna, 17164

  • Centrallasarettet i Växjö

    Vaxjo, 351 85

Other trials in Sweden

United Kingdom3 sites

  • Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED

  • Guy's Hospital

    London, SE1 9RT

  • Royal Marsden Foundation Trust

    London, SW3 6JJ

Other trials in United Kingdom

Netherlands2 sites

  • Leids Universitair Medisch Centrum

    Leiden, 2333 ZA

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584CX

Other trials in Netherlands

About this study

Official title: 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

Read the 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

Being tested
Ipilimumab, Tilsotolimod with Ipilimumab
Keywords
Melanoma, PD1, PD-1, refractory, metastatic, IMO-2125, illuminate 301, TLR9 agonist, advanced melanoma, CTLA4, CTLA-4, immunotherapy, skin cancer, ILLUMINATE-301
Medical subject headings
Melanoma, Neoplasm Metastasis, Diabetes Mellitus, Insulin-Dependent, 12, Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabDrug

    Also called Yervoy®

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

  • Tilsotolimod with IpilimumabDrug

    Also called IMO-2125 with Yervoy

    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

Study groups in NCT03445533
Study groupRoleWhat they receive
Arm A: ipilimumabExperimentalipilimumab 3 mg/kg intravenous
Receives: Drug: Ipilimumab
Arm B: IMO-2125 plus ipilimumabExperimentalIMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous
Receives: Drug: Tilsotolimod with Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).

  2. 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.

    Measured: OS is measured from the date of randomization to the date of death from any cause (up to 36 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2018
  2. Study start30 May 2018
  3. Primary completion1 Jun 2021
  4. Study completion1 Jun 2021

Why it stopped: Lack of Efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
481 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03445533
Sponsor's protocol ID
2125-MEL-301
Status last verified
Oct 2022
First submitted
13 Feb 2018
Last updated
8 Nov 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40048691

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ipilimumab and Tilsotolimod with Ipilimumab in people with Metastatic Melanoma, run by Idera Pharmaceuticals, Inc. at 80 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, Italy, France, Spain, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 (time frame: Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03445533, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.

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