Clinical trial NCT03445533: A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
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
Lead sponsor: Idera Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-02-26
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1
timeFrame: Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).
measure: Summary of Overall Survival
timeFrame: OS is measured from the date of randomization to the date of death from any cause (up to 36 months).
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB)
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Scottsdale
country: United States
facility: Cancer Treatment Centers of America (CTCA) - Western Regional Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: Sacramento
country: United States
facility: Sutter Health Sacramento
state: California
city: San Diego
country: United States
facility: University of California, San Diego (UCSD) - Moores Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center of Florida, Inc.
state: Florida
city: Orlando
country: United States
facility: University of Florida Health Cancer Center - Orlando Health
state: Florida
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Cincinnati
country: United States
facility: University of Cincinnati Health
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Falls Church
country: United States
facility: Inova Health Care Services
state: Virginia
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Center
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woodville South
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Geelong
country: Australia
facility: University Hospital Geelong
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Health Services Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Hopsital
state: Ontario
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc - Oncology clinic
city: Praha
country: Czechia
facility: Dermatovenerologika Klinika
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Clermont-Ferrand
country: France
facility: CHU - Clermont Ferrand
state: Cedex
city: Rouen
country: France
facility: CHRU Besançon - Jean Minjoz
state: Cedex
city: Amiens
country: France
facility: CHU Amiens Picardie - Hopital Sud
city: Dijon
country: France
facility: CHU Dijon - Hôpital Mitterrand
city: La Tronche
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de Marseille - Hopital de la Timone
city: Paris
country: France
facility: Hopital Saint Louis
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: CHU Hopitaux de Rouen
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Buxtehude
country: Germany
facility: Elbe Kliniken
city: Hannöver
country: Germany
facility: Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg Universitaets-Hautklinik
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Regensburg
country: Germany
facility: Universitatsklinikum Regensburg
city: Tübingen
country: Germany
facility: Universität Tübingen
city: Würzburg
country: Germany
facility: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universität Würzburg
city: Bari
country: Italy
facility: Azienda Ospedale Policlinico di Bari
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Genova
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino IST
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale di Tumori IRCCS "Fondazione Sen. G. Pascale"
city: Padova
country: Italy
facility: Istituto Oncologico Veneto-I.R.C.C.S.
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
city: Siena
country: Italy
facility: Azienda Ospedaliero Universitaria Senese
city: Torino
country: Italy
facility: Universita di Torino
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruna
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Donostia
country: Spain
facility: Onkologikoa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Consorci Hospital General Universitari de Valencia
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus i Lund
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Växjö
country: Sweden
facility: Centrallasarettet i Växjö
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Marsden Foundation Trust
Study officials:
affiliation: Idera Pharmaceuticals, Inc.
name: Idera Medical Director
role: STUDY_DIRECTOR
References: