IOV-3001 for Melanoma

Recruiting at 1 trial location

Overseen By Iovance Biotherapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Iovance Biotherapeutics, Inc.

Must be taking: PD-1/PD-L1 blockers

Must not be taking: Systemic steroids

Disqualifiers: Brain metastases, Infections, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IOV-3001 for individuals with melanoma that cannot be surgically removed or has metastasized. The goal is to determine if this treatment can benefit those who have not responded to other therapies, such as PD-1/PD-L1 blockers. The trial seeks participants with melanoma, excluding those with eye-related melanoma, who have experienced disease progression after previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy at a dose of 10 mg/day prednisone or equivalent, you may not be eligible to participate.

Is there any evidence suggesting that IOV-3001 is likely to be safe for humans?

Research has shown that IOV-3001 might be safer than other treatments, potentially being gentler on the body and requiring less frequent dosing. However, as this trial is in its early stages, the researchers are closely monitoring the safety of IOV-3001. Early-phase trials typically focus on assessing the safety of new treatments for people.

The treatment will be administered alongside lifileucel, which the FDA has approved for treating advanced melanoma. This approval indicates that lifileucel is considered safe for people. Participants in the trial will receive both treatments to evaluate their combined effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for melanoma, such as immunotherapies like pembrolizumab or targeted therapies like vemurafenib, IOV-3001 acts on a different front. Researchers are excited about IOV-3001 because it introduces a novel approach by potentially targeting specific pathways or mechanisms not addressed by existing therapies. This innovative angle could offer new hope for patients with unresectable or metastatic melanoma who have limited options. By offering a fresh mechanism of action, IOV-3001 may provide an effective alternative for those whose cancers don't respond to current treatments.

What evidence suggests that IOV-3001 might be an effective treatment for melanoma?

Research has shown that IOV-3001, a modified protein, may help treat advanced melanoma. Early studies suggest it could be safer than traditional treatments, potentially causing fewer or less severe side effects. This treatment aids the immune system in fighting cancer cells. Although complete data on its efficacy is not yet available, these early results offer hope for those with limited treatment options. Participants in this trial will receive IOV-3001 as part of the dose escalation study for unresectable or metastatic melanoma. ^{1 4 6 7 8}

Who Is on the Research Team?

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Are You a Good Fit for This Trial?

Adults with advanced melanoma that can't be removed by surgery or has spread, who have previously been treated and didn’t respond well to PD-1/PD-L1 blocking antibodies. They must be over 18, in good physical condition (ECOG status of 0 or 1), and expected to live more than 6 months. People with eye melanoma can join only part of the trial if they've tried tebentafusp.

Inclusion Criteria

My melanoma cannot be removed by surgery or has spread.

My melanoma has worsened despite PD-1/PD-L1 therapy, and I've had or declined BRAF/MEK inhibitors if applicable.

I am mostly active and expected to live more than 6 months.

Exclusion Criteria

I have brain metastases that haven't been treated and are causing symptoms.

I have had an organ transplant or cell therapy after chemo in the last 20 years.

Participant has a history of hypersensitivity to any component of the study intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Phase 1

Participants receive IOV-3001 either before or after the Lifileucel regimen

Up to 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• IOV-3001

Trial Overview The study is testing IOV-3001, a modified protein aimed at boosting the immune system, alongside lifileucel therapy for those whose melanoma has worsened despite prior treatments. It's an early-stage trial where everyone gets the experimental treatment.

How Is the Trial Designed?

Group I: Assigned Interventions Experimental Treatment 1 Intervention

Dose escalation participants with unresectable or metastatic melanoma

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

The CheckMate 511 study found that using nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) resulted in a significantly lower incidence of severe treatment-related adverse events (34%) compared to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) which had a 48% incidence (P = .006).

While the efficacy outcomes such as objective response rate (45.6% for NIVO3+IPI1 vs. 50.6% for NIVO1+IPI3) and median progression-free survival (9.9 months vs. 8.9 months) were similar between the two groups, the NIVO3+IPI1 regimen showed a better safety profile without compromising effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial. Lebbé, C., Meyer, N., Mortier, L., et al.[2020]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

Ipilimumab, while used for melanoma treatment, has a high rate of severe adverse events (over 50% of patients), making it less favorable compared to newer options.

BRAF inhibitors, particularly when combined with mitogen-activated protein kinase inhibitors, show greater efficacy and a better safety profile than ipilimumab, but are only effective in about 50% of melanoma cases with a specific BRAF gene mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous melanoma: Latest developments. Dixon, AJ., Steinman, HK., Nirenberg, A., et al.[2020]

The combination of ipilimumab (IPI) and nivolumab (NIVO) with percutaneous hepatic perfusion of melphalan (M-PHP) was found to be safe for patients with metastatic uveal melanoma, with no dose-limiting toxicities reported in a study involving 7 patients over a treatment duration of 12 weeks.

The defined safe doses were IPI at 1 mg/kg and NIVO at 3 mg/kg, resulting in promising outcomes with 1 complete response, 5 partial responses, and 1 stable disease, indicating potential efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial. Tong, TML., Burgmans, MC., Speetjens, FM., et al.[2023]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

Vemurafenib is associated with a higher incidence of acute kidney injury compared to dabrafenib, with 132 reported cases during the study period, particularly affecting male patients.

Both drugs can cause electrolyte imbalances, such as hypokalemia and hyponatremia, indicating the importance of monitoring renal function and electrolyte levels in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephrotoxicity of the BRAF Inhibitors Vemurafenib and Dabrafenib. Jhaveri, KD., Sakhiya, V., Fishbane, S.[2022]

This case study presents the first instance of combining immune checkpoint blockade (ICB) with Talimogene laherparepvec (T-VEC) in a patient suffering from both primary cutaneous anaplastic large cell lymphoma (pcALCL) and metastatic melanoma, showcasing the complexities of treating patients with multiple cancers.

The patient experienced rapid progression of pcALCL while on nivolumab, an anti-PD-1 therapy, and developed a novel adverse effect, Kaposi's varicelliform eruption, after the first dose of T-VEC, indicating potential safety concerns when using this treatment in patients with concurrent malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi's varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab. Miller, DM., Trowbridge, RM., Desai, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06940739

A Study to Investigate the Safety and Efficacy of IOV-3001 ... A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel. ClinicalTrials.gov ID NCT06940739.

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/598419

A Study to Investigate the Safety and Efficacy of IOV-3001 ... A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel ; Phase. I / II ; Age. 18- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2552

IOV-3001, a modified interleukin-2 fusion protein, for ... IOV-3001 showed a favorable preclinical safety profile. These results suggest a potentially improved safety profile for IOV-3001 with less ...

4. ir.iovance.com ir.iovance.com/node/15301/pdf

Iovance Biotherapeutics Reports Financial Results and ... 1 Iovance is gaining momentum to address adult patients with previously treated advanced melanoma in new markets. Health Canada is expected to ...

5. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/IOVA/pressreleases/35737211/iovance-biotherapeutics-advances-melanoma-treatment-with-new-study/

Iovance Biotherapeutics Advances Melanoma Treatment ... This research is significant as it explores new therapeutic options for melanoma patients with limited treatment alternatives. Intervention/ ...

6. iovance.com iovance.com/uploads/Simpson-ASCO-2024-IOV-3001-Preclinical-Poster_D5-APP-2756-publication.pdf

IOV-3001, a modified interleukin-2 fusion protein, for ... • Overall, these data suggest that IOV-3001 may have a better safety profile and may require less frequent dosing in humans compared with.

7. withpower.com withpower.com/trial/phase-2-melanoma-2-2025-2a5d7

IOV-3001 for Melanoma · Recruiting Participants for Phase ... What safety data exists for IOV-3001 (nivolumab) in melanoma treatment? Nivolumab, used for treating melanoma, has been generally safe in humans, with some ...

8. sec.gov sec.gov/Archives/edgar/data/1425205/000110465925075175/tm2522769d1_ex99-1.htm

99.1 The U.S. FDA approved Amtagvi (lifileucel) on February 16, 2024, as the first treatment option for patients with advanced (unresectable or ...