A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (p) T3-4 cN0M0 Melanoma (INTRIM)

A Randomized Controlled Phase II Clinical Trial With Intradermal IMO-2125 (Tilsotolimod) in pT3-4 cN0M0 Melanoma

Currently, there is no widely used adjuvant treatment available to improve survival after surgical excision of a primary melanoma. In a previous study, loco-regional and systemic immune stimulations, as well as favourable clinical outcomes in terms of sentinel lymph node (SLN) tumor status and recurrence-free survival (RFS) in patients with clinical stage I-II melanoma who received a low dose of toll-like receptor 9 (TLR-9) CPG7909 (CpG-B ODN) intradermally at the excision site of the primary tumor prior to SLN biopsy (SNB) were described. In this phase II trial the investigators had investigated the clinical activity of a next-generation CpG-ODN, IMO-2125, and it's ability to induce loco-regional and systemic immune stimulation in pT3-4 cN0M0 melanoma patients who are scheduled to undergo a combined re-excision and SNB is

Study Overview

• Status: Recruiting
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: Tilsotolimod; Drug: Saline (0.9% sodium chloride)

• Study Type: Interventional
• Enrollment (Anticipated): 214
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jessica CL Notohardjo, MD; Phone Number: +3120 4444881; Email: intrim@vumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VU Medical Centere

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years or older
• Histologically confirmed primary malignant melanoma cutis with a Breslow tumor depth >2.0 mm
• Scheduled to undergo a combines re-excision and sentinel node biopsy (SNB)
• World Health Organization (WHO) Performance Status ≤1
• Agreement to use effective contraceptive methods from screening until at least 90 days after the IMO-2125 administration
• Written informed consent

Exclusion Criteria:

• Known hypersensitivity to any oligodeoxynucleotide
• Active auto-immune disease requiring disease-modifying therapy at the tumr of screening
• Pathologically confirmed loco-regional or distant metastasis
• Non-skin melanoma
• Patients with another primary malignancy (some exceptions)
• Active systemic infections requiring antibiotics
• Women who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tilsotolimod (IMO-2125); Intradermal, single injection of 1 ml (8 mg) Tilsotolimod (IMO-2125) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).	Drug: Tilsotolimod; Intradermal, single injection of 1 ml (8 mg) Tilsotolimod (IMO-2125) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).; Other Names: IMO-2125
Placebo Comparator: Placebo; Intradermal, single injection of 1 ml plain saline (0.9% sodium chloride) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).	Drug: Saline (0.9% sodium chloride); Intradermal, single injection of 1 ml plain saline (0.9% sodium chloride) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of tumor positive sentinal lymph node (SLN)	The rate of tumor positive sentinal lymph node (SLN)	Seven days after the intradermal injection of Tilsotolimod (IMO-2125)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response in the SLN and peripheral blood	Frequency and activation state of lymph node resident (LNR) conventional dendritic cells (DC) and melanoma antigen-specific T cell responses in the SLN and peripheral blood.	Seven days after the intradermal injection of Tilsotolimod (IMO-2125)
Recurrence free survival (RFS)	The length of time from intradermal injection of Tilsotolimod (IMO-2125) to first documentation of recurrence.	At 5 years and 10 years after sentinel node biopsy (SNB)
Overall survival	The length of time from intradermal injection of Tilsotolimod (IMO-2125) to death from any cause.	At 5 years and 10 years after sentinel node biopsy (SNB)

Collaborators and Investigators

• Sponsor: A.J.M. van den Eertwegh
• Collaborators: Idera Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Tanja de Gruijl, Amsterdam Umc, Location Vumc

Publications and helpful links

General Publications

• Koster BD, van den Hout MFCM, Sluijter BJR, Molenkamp BG, Vuylsteke RJCLM, Baars A, van Leeuwen PAM, Scheper RJ, Petrousjka van den Tol M, van den Eertwegh AJM, de Gruijl TD. Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I-II Melanoma: Data from Two Randomized Phase II Trials. Clin Cancer Res. 2017 Oct 1;23(19):5679-5686. doi: 10.1158/1078-0432.CCR-17-0944.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2031

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2018/418

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No