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

Metastatic Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03445533
• Other study ID #: 2125-MEL-301
• Status: Terminated
• Phase: Phase 3
• Start date: May 30, 2018
• Est. completion date: June 1, 2021

Study information

• Verified date: October 2022
• Source: Idera Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 481
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)-a 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.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• Ipilimumab
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 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

Locations

Country	Name	City	State
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Icon Cancer Center	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Queen Elizabeth Hospital	Woodville South	South Australia
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Alberta Health Services Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Hopsital	Toronto	Ontario
Czechia	Fakultni nemocnice Olomouc - Oncology clinic	Olomouc
Czechia	Dermatovenerologika Klinika	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
France	CHU Amiens Picardie - Hopital Sud	Amiens
France	CHU - Clermont Ferrand	Clermont-Ferrand	Cedex
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 Cedex 08
France	CHU de Marseille - Hopital de la Timone	Marseille
France	Hopital Saint Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	CHRU Besançon - Jean Minjoz	Rouen	Cedex
France	CHU Hopitaux de Rouen	Rouen
France	Institut Gustave Roussy	Villejuif
Germany	Klinikum Augsburg	Augsburg
Germany	Charite Universitaetsmedizin Berlin	Berlin
Germany	Elbe Kliniken	Buxtehude
Germany	Medizinische Hochschule Hannover - Klinik for Dermatologie, Allergologie und Venerologie	Hannöver
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
Italy	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	Milano
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.	Padova
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
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Spain	Hospital Universitario A Coruna	A Coruña
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitari Quiron Dexeus Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Onkologikoa	Donostia
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Consorci Hospital General Universitari de Valencia	Valencia
Sweden	Skånes Universitetssjukhus i Lund	Lund
Sweden	Karolinska Universitetssjukhuset	Solna
Sweden	Centrallasarettet i Växjö	Växjö
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Guy's Hospital	London
United Kingdom	Royal Marsden Foundation Trust	London
United States	University of Alabama at Birmingham (UAB)	Birmingham	Alabama
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	Inova Health Care Services	Falls Church	Virginia
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	University of Southern California	Los Angeles	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	Sutter Health Sacramento	Sacramento	California
United States	University of California, San Diego (UCSD) - Moores Cancer Center	San Diego	California
United States	Cancer Treatment Centers of America (CTCA) - Western Regional Medical Center	Scottsdale	Arizona
United States	Stanford Cancer Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Idera Pharmaceuticals, Inc.	Bristol-Myers Squibb

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).

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