MelanomaPhase 2NCT03711188

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

A Phase 2 study testing Nivolumab, Ipilimumab and IMM-101 in people with Melanoma, run by Immodulon Therapeutics Ltd at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Melanoma
What is being tested?: Nivolumab, Ipilimumab and IMM-101
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 2 sitesUnited Kingdom
Study dates: 4 Oct 2018to 2 Dec 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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For cohort A, the following key inclusion criteria apply:
1. Patient is treatment-naive (i.e. no prior systemic anticancer therapy for unresectable or metastatic melanoma).
For cohort B, the following key inclusion criteria apply:
1. 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.

Who cannot join

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:
1. 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:
1. Patient has received more than one treatment regimen for advanced (stage III/IV) disease prior to their anti PD-1 therapy.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

St George's University Hospitals NHS Foundation Trust
London, SW17 0QT
The Christie Hospital
Manchester, M20 4BX

Other trials in United Kingdom

About this study

Official title: A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma

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

Read the detailed description

This open-label study will assess the safety and efficacy of the combination of IMM-101 with nivolumab in patients with unresectable stage III, or stage IV melanoma who are either treatment-naive (cohort A) or whose disease has progressed during PD-1 blockade (cohort B). Ipilimumab may be used as a subsequent treatment in place of nivolumab alongside IMM-101 for patients in cohort B if their disease progresses on study. Eighteen patients will be enrolled into cohort A and 8 patients into cohort B.

Conditions: Melanoma
Being tested: Nivolumab, Ipilimumab, IMM-101
Medical subject headings: Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo
Nivolumab is to be administered as a 3 mg/kg IV infusion every two weeks in accordance with the prescribing information.
IpilimumabDrug
Also called Yervoy
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.
IMM-101Drug
Also called Heat killed whole cell M. obuense National Collection of Type Cultures (NCTC) 13365
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.

Study groups in NCT03711188
Study group	Role	What they receive
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. Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: IMM-101

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety and Tolerability of the Combination of IMM-101 + Nivolumab
Incidence, frequency and severity of treatment emergent adverse events (TEAEs) throughout the study.
Measured: 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).
Measured: From enrollment to end of study (18 months) or withdrawal, whichever was soonest

Secondary outcomes (4)

Best Overall Response (BOR) Using RECIST 1.1
Best Overall Response (BOR) is defined as the best response (complete or partial response, stable disease or progressive disease) 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).) Patients in cohort B who changed therapy without documented progression were censored at their last scan assessment prior to the change of therapy.
Measured: 18 months
Progression Free Survival (PFS)
Progression-free survival was defined as the time from Visit 1 (week 0) to the first confirmation of progression using RECIST 1.1 (confirmed or unconfirmed), or death from any cause (whichever occurred first). Progression was determined by the investigator using the CT or MRI scan or death due to any cause. Patients who died without reporting progression were considered to have progressed on the date of their death. Progression is defined by RECIST 1.1 guidelines as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Measured: 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 date of death from any cause. OS was calculated for the entire study duration, where patients without a death date were right censored at the date the patient was last known to be alive. Post-study survival information was collected until database lock, for subjects completing or withdrawing from the study and included in the analysis.
Measured: 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
Number of patients surviving at leat 12 months
Measured: OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Oct 20182 Dec 2021

First posted18 Oct 2018
Study start4 Oct 2018
Primary completion2 Dec 2021
Study completion2 Dec 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MelanomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03711188
Sponsor's protocol ID: IMM-101-015
Status last verified: Nov 2023
First submitted: 4 Oct 2018
Last updated: 29 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 29 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study of the Safety and Efficacy of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma
ClinicalTrials.gov ID: NCT03711188
Acronym / sponsor ID: IMM-101-015
Conditions: Melanoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Immodulon Therapeutics LtdIndustry (pharma, biotech, devices)
Study start: 4 Oct 2018 (actual)
Primary completion: 2 Dec 2021 (actual)
Study completion: 2 Dec 2021 (actual)
First posted: 18 Oct 2018 (actual)
Results: Posted 29 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
IMM-101 (and nivolumab or ipilimumab)	Experimental	Drug: Nivolumab, Drug: Ipilimumab, Drug: IMM-101Patients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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.

Key exclusion criteria (8 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NivolumabAlso: OpdivoNivolumab is to be administered as a 3 mg/kg IV infusion every two weeks in accordance with the prescribing information.	Drug	IMM-101 (and nivolumab or ipilimumab)
IpilimumabAlso: YervoyIpilimumab, 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.	Drug	IMM-101 (and nivolumab or ipilimumab)
IMM-101Also: Heat killed whole cell M. obuense National Collection of Type Cultures (NCTC) 13365A 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.	Drug	IMM-101 (and nivolumab or ipilimumab)

Primary outcome

Safety and Tolerability of the Combination of IMM-101 + Nivolumab
Time frame: From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.
Incidence, frequency and severity of treatment emergent adverse events (TEAEs) throughout the study.
Overall Response Rate
Time frame: From enrollment to end of study (18 months) or withdrawal, whichever was soonest
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).

4 secondary outcomes

Best Overall Response (BOR) Using RECIST 1.1
Time frame: 18 months
Progression Free Survival (PFS)
Time frame: 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)
Time frame: 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
Time frame: OS at 1 year was calculated after all patients had had the opportunity of 12 months treatment of study

Results and safety

Results posted to the registry on 29 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IMM-101 (and Nivolumab or Ipilimumab)	16	4

Primary outcome: Safety and Tolerability of the Combination of IMM-101 + Nivolumab

Time frame: From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.. Count of participants. Unit: Participants

Measure	IMM-101 (and Nivolumab or Ipilimumab) n = 16
Treatment emergent adverse events (TEAEs)	16
Treatment-related TEAEs	14
Serious TEAEs	6
Immune relared TEAEs	14
TEAEs leading to discontinuation of IMM-101	3
TEAEs leading to withdrawal	1
TEAEs leading to death	0

Population analysed: The Safety Analysis Set (SAF) included all patients who received at least one dose of IMM-101, irrespective of compliance with eligibility and other protocol criteria.

Primary outcome: Overall Response Rate

Time frame: From enrollment to end of study (18 months) or withdrawal, whichever was soonest. Count of participants. Unit: Participants

Measure	Cohort A n = 11	Cohort B n = 5
Value	8	0

Population analysed: Intent-to-treat

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events (AEs) were recorded on the patient's electronic case report form (eCRF) from the time of informed consent until the end of study (18 months later) . All AEs were followed until resolution, death, or 30 days after the last administration of study treatment (whichever came first).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IMM-101 and Nivolumab	12 of 16 (75%)	16 of 16 (100%)	8 of 16
IMM-101 and Ipilimumab	1 of 1 (100%)	1 of 1 (100%)	1 of 1

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alberto Fusi principal investigator

St George's University Hospitals NHS Foundation Trust

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Ipilimumab and IMM-101 in people with Melanoma, run by Immodulon Therapeutics Ltd at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of the Combination of IMM-101 + Nivolumab (time frame: From the point of Informed Consent until end of the study assessment (up to 84 weeks) or until withdrawal from the study.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03711188.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2024.