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

Trial Summary

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.

What data supports the effectiveness of the drug IOV-3001 for melanoma?

Research shows that targeted therapies and immuno-oncology drugs, which are similar to IOV-3001, have been effective in treating melanoma, with targeted therapies showing a higher response rate and longer treatment duration in patients with BRAF mutations. ^{1 2 3 4 5}

What safety data exists for IOV-3001 (nivolumab) in melanoma treatment?

Nivolumab, used for treating melanoma, has been generally safe in humans, with some patients experiencing manageable side effects. In studies, serious side effects occurred in a small number of patients, but these were typically manageable with early diagnosis and treatment. ^{6 7 8 9 10}

How is the treatment IOV-3001 different from other melanoma treatments?

IOV-3001 is unique because it involves the use of oncolytic viruses, which are viruses engineered to selectively infect and kill cancer cells, potentially activating the body's immune response against the tumor. This approach is different from traditional chemotherapy or targeted therapies, as it uses a virus to directly attack cancer cells and stimulate an immune response. ^{11 12 13 14 15}

What is the purpose of this trial?

A Phase 1/2, open-label study of a modified interleukin-2 fusion protein (IOV 3001) in participants with previously treated, unresectable or metastatic melanoma who will receive lifileucel.

Research Team

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Cutaneous melanoma: Latest developments. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Nephrotoxicity of the BRAF Inhibitors Vemurafenib and Dabrafenib. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Imaging Intensity and Survival Outcomes in High-Risk Resected Melanoma Treated by Systemic Therapy at Recurrence. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Targeted agents or immuno-oncology therapies as first-line therapy for BRAF-mutated metastatic melanoma: a real-world study. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Novel agents in development for the treatment of melanoma. [2019]

6. United States 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. [2023]

7. United States 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of intravenous administration of Reolysin(®) (Reovirus Serotype-3-dearing Strain) in patients with metastatic melanoma. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Engineered oncolytic viruses to treat melanoma: where are we now and what comes next? [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, coxsackievirus a21. [2019]

14. England pubmed.ncbi.nlm.nih.gov

Pro-inflammatory cytokine/chemokine production by reovirus treated melanoma cells is PKR/NF-κB mediated and supports innate and adaptive anti-tumour immune priming. [2022]

15. England 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. [2019]