A Study of IMO-2125 in Combination With Ipilimumab Versus Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (ILLUMINATE-301)

Sponsor

Idera Pharmaceuticals, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03445533

Collaborator

Bristol-Myers Squibb (Industry)

481

Enrollment

Locations

Arms

36.1

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma	Drug: Ipilimumab Drug: IMO-2125 Drug: Ipilimumab	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

481 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 30, 2018

Actual Primary Completion Date :

Jun 1, 2021

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: ipilimumab ipilimumab 3 mg/kg intravenous	Drug: Ipilimumab 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: IMO-2125 IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. Drug: Ipilimumab Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. Other Names: Yervoy

Arm

Intervention/Treatment

Experimental: Arm A: ipilimumab

ipilimumab 3 mg/kg intravenous

Drug: Ipilimumab

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: IMO-2125

IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24.

Drug: Ipilimumab

Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11.

Other Names:

Yervoy

Outcome Measures

Primary Outcome Measures

Compare the efficacy of IMO-2125 in combination with ipilimumab versus ipilimumab alone [OS is measured from the date of randomization to the date of death from any cause (up to 56 months).]
Efficacy measured by overall survival (OS)
Compare the efficacy of IMO-2125 in combination with ipilimumab versus ipilimumab alone [Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).]
Efficacy measure by overall response rate (ORR)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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)
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).

Exclusion Criteria:

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.

Contacts and Locations

Locations

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