What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving PD-1 pathway inhibitors like Nivolumab, are associated with immune-related adverse events (irAEs) such as skin reactions, gastrointestinal issues, hepatic problems, and endocrine disturbances. When combined with other agents like ipilimumab, the severity of side effects can increase, including higher rates of grade 3 or 4 toxicities. Radiation therapy can further exacerbate these immune-related side effects, especially skin reactions. The combination of PD-1 inhibitors with novel agents like Anti-IL-8 is still being studied, but similar inflammatory responses are expected.

What prior FDA approvals exist?

The FDA has approved several drugs targeting the PD-1 pathway for the treatment of melanoma. Nivolumab and pembrolizumab are both PD-1 inhibitors that have shown efficacy in treating advanced melanoma. Nivolumab has been approved for use both as a monotherapy and in combination with ipilimumab, a CTLA-4 inhibitor, for enhanced efficacy. Pembrolizumab has also been approved for use in various dosing schedules. These treatments have demonstrated improved progression-free survival and overall survival in patients with advanced melanoma. While the combination of nivolumab and anti-IL-8 (BMS-986253) with radiation is still under investigation, the existing approvals of PD-1 inhibitors highlight the potential of this pathway in melanoma treatment.

What other types of research exist?

Promising alternatives to Nivolumab and Anti-IL-8 (BMS-986253) with radiation for melanoma patients include combinations of Pembrolizumab (another PD-1 inhibitor) with Ipilimumab (a CTLA-4 inhibitor), as well as experimental approaches like CAR-T cell therapies. These combinations and novel therapies are being actively researched and may offer effective treatment options in 2024.

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Other

Immunotherapy + SBRT for Solid Cancers

Phase 1

Recruiting

Led By Jason Luke, MD, FACP

Research Sponsored by Jason J. Luke, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

EFFICACY COHORT: Patients with 1-4 tumor sites that can be irradiated safely

EFFICACY COHORT: ECOG performance status 0 or 1

Must not have

Presence of certain medical conditions and malignancies

Subjects who are on immunosuppressive therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment combining radiation, nivolumab, and BMS-986253 for patients with advanced cancers who haven't responded to other treatments. The goal is to find safe doses and see if this combination can help the immune system fight cancer more effectively. Nivolumab, often combined with ipilimumab, has shown promising results in improving survival rates in various cancers, including melanoma.

Who is the study for?

This trial is for adults with advanced solid tumors like melanoma or renal cell carcinoma, who have progressed on standard therapies. They must be able to undergo radiation, have normal organ function, and not be pregnant or breastfeeding. Participants need detectable IL-8 levels in their blood and an ECOG performance status of 0 or 1.

What is being tested?

The study tests the safety of combining Stereotactic Body Radiotherapy (SBRT) with two immunotherapy drugs: Nivolumab (anti-PD1) and BMS-986253 (anti-IL-8). It aims to find safe radiation doses by organ site when used with these drugs and observe changes in tumor environments.

What are the potential side effects?

Potential side effects include typical immune-related reactions such as inflammation in various organs, fatigue, skin issues, flu-like symptoms, hormonal gland problems, and possible infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have 1-4 tumors that can be safely treated with radiation.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My organ and bone marrow functions are normal.

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I am 18 years old or older.

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My cancer can be measured by tests or scans.

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I have 1 to 4 tumors that can be safely treated with radiation.

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My cancer can be measured by tests or scans.

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My organs and bone marrow are functioning normally.

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My melanoma or kidney cancer has not responded to anti-PD1/PDL1 treatment.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have specific health conditions or cancers.

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I am currently on medication to suppress my immune system.

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I haven't had encephalitis, meningitis, or uncontrolled seizures in the last year.

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I am currently being treated for an infection.

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I do not have major heart problems.

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I cannot have blood drawn or tolerate needles in my veins.

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I have had a severe reaction to previous immune therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Rate of Dose Limiting Toxicities (DLT)

Secondary study objectives

Incidence of grade 3 or higher adverse events

Local tumor control (RECIST v1.1)

Neoplasms

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Nivolumab (Anti-PD-1) + BMS-986253 (Anti-IL-8) + SBRTExperimental Treatment3 Interventions

480 mg intravenous nivolumab (BMS-936558-01) every 4 weeks + 2,400 mg intravenous BMS-986253 (Anti-IL-8) every 2 weeks + Stereotactic Body Radiotherapy (SBRT)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

BMS-986253

2020

Completed Phase 2

~50

nivolumab

2016

Completed Phase 3

~4960

Stereotactic Body Radiotherapy (SBRT)

2017

Completed Phase 3

~550

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for melanoma include immune checkpoint inhibitors like Nivolumab, which targets the PD-1 pathway, and Ipilimumab, which targets CTLA-4. These inhibitors work by blocking proteins that prevent T-cells from attacking cancer cells, thereby enhancing the immune system's ability to fight the tumor. The combination of Nivolumab and Anti-IL-8 (BMS-986253) with radiation aims to further improve response rates by not only inhibiting the PD-1 pathway but also reducing inflammation and altering the tumor microenvironment through IL-8 inhibition. This multi-faceted approach is crucial for melanoma patients as it can potentially lead to more effective and durable responses, especially in those who do not respond to monotherapy.