A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma

NCT03711188 | Completed Phase 2 Results

• 1 other identifier: IMM-101-015
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety and efficacy of the combination of IMM-101 with nivolumab.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of the Combination of IMM-101 + Nivolumab

  Incidence, frequency and severity of treatment emergent adverse events (TEAEs) throughout the study.

  From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.

• Overall Response Rate

  The primary endpoint of Overall Response Rate (ORR) is defined as the number of subjects with a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of subjects in the Intent-to-treat analysis set in each cohort of the study. The BOR will be determined once all the data up to and including the 12-month assessments for Cohort A or the 6-month assessment for Cohort B are available. It is defined as the best response designation based on confirmed responses determined by the investigator according to RECIST 1.1, recorded between the date of first postscreening scan and the date of last scan at/prior to the assessment at the 12-month assessment (Cohort A) and 6-month assessment/last assessment prior to change of treatment to IMM-101 + ipilimumab whichever is sooner (Cohort B).

  From enrollment to end of study (18 months) or withdrawal, whichever was soonest

Secondary Outcomes (4)

• Best Overall Response (BOR) Using RECIST 1.1

  18 months

• Progression Free Survival (PFS)

  From Visit 1 (week 0) and the first confirmation of progression using RECIST 1.1 (confirmed or unconfirmed), or death from any cause (whichever occurred first).

• Overall Survival (OS)

  Overall survival was defined as the time from Visit 1 (week 0) until the end of the study (80 weeks) or until the date of death from any cause.

• Overall Survival (OS) at One Year

  OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study

Study Arms (1)

IMM-101 (and nivolumab or ipilimumab)

EXPERIMENTAL

Patients in cohort A were given IMM-101 in combination with nivolumab. Patients in cohort B who fail to respond to treatment with IMM-101 and nivolumab, and who meet certain criteria, have the option to change treatment on study to IMM-101 and ipilimumab.

Drug: Nivolumab; Drug: Ipilimumab; Drug: IMM-101

Interventions

Nivolumab DRUG

Nivolumab is to be administered as a 3 mg/kg IV infusion every two weeks in accordance with the prescribing information.

Also known as: Opdivo

IMM-101 (and nivolumab or ipilimumab)

Ipilimumab DRUG

Ipilimumab, when used as subsequent treatment for patients in cohort B, is to be administered as a 3 mg/kg IV infusion over 90 minutes every three weeks for a maximum of 4 doses, in accordance with the prescribing information.

Also known as: Yervoy

IMM-101 (and nivolumab or ipilimumab)

IMM-101 DRUG

A single 0.1 mL intradermal injection of IMM 101 (10 mg/mL) given every 2 weeks for the first 3 doses followed by a rest period of 4 weeks, then one dose every 2 weeks for the next 3 doses. This is followed by a dose every 4 weeks thereafter.

Also known as: Heat killed whole cell M. obuense National Collection of Type Cultures (NCTC) 13365

IMM-101 (and nivolumab or ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma.
• At least one measurable lesion by CT or MRI, according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) Performance Status of ≤1 at Day 0.
• Known BRAF V600 mutation status or consent to BRAF V600 mutation testing during the Screening Period.
• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration (Week 0, Visit 1). Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to enrolment (Week 0, Visit 1), and all related adverse events have resolved or stabilised.
• Patient is considered suitable for treatment with nivolumab.
• \. Patient is treatment-naive (i.e. no prior systemic anticancer therapy for unresectable or metastatic melanoma).
• \. Patient is either currently receiving treatment with an anti-PD-1 therapy (monotherapy or in combination with ipilimumab), for advanced melanoma and has progressive disease by RECIST 1.1 after 4 or more doses; or has previously received at least 4 doses of PD-1 targeted therapy, alone or in combination with ipilimumab, had disease progression by RECIST 1.1 during this therapy and has not received any further therapy for advanced melanoma.

You may not qualify if:

• Uveal/ocular melanoma.
• Active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible for cohort B of the study only, if these have been treated and there is no MRI evidence of progression for at least 8 weeks after treatment is complete and within 21 days prior to first dose of study treatment administration.
• Patient has documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents.
• Patient has a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressant drugs (such as azathioprine, tacrolimus, cyclosporin) within the 14 days period before the first administration of IMM-101.
• For cohort A, patients meeting the following key criteria are also ineligible to participate in this study:
• \. Patient has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-PD ligand-1 (PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent.
• For cohort B, patients meeting the following key criteria are also ineligible to participate in this study:
• \. Patient has received more than one treatment regimen for advanced (stage III/IV) disease prior to their anti PD-1 therapy.

Sponsors & Collaborators

• Immodulon Therapeutics Ltd: lead

Study Sites (2)

St George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Ipilimumab; IMM-101

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The Overall Response Rate shows encouraging results in Cohort A with 73% of responses confirmed by subsequent scans (18% patients had a BOR (RECIST 1.1) of complete response (CR) and 55% of partial response (PR)). Limitations are the small sample size. This finding would need to be confirmed in a larger trial.

Results Point of Contact

• Title: Clinical Trial Information Desk,
• Organization: Immodulon Therapeutics Ltd

info@immodulon.com

0044 0203137 6346

Study Officials

• Alberto Fusi

  St George's University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2018
• First Posted: October 18, 2018
• Study Start: October 4, 2018
• Primary Completion: December 2, 2021
• Study Completion: December 2, 2021
• Last Updated: April 29, 2024
• Results First Posted: April 29, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)