IO102/IO103 + Nivolumab-Relatlimab for Melanoma

Not currently recruiting at 8 trial locations

Overseen By James Smithy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Immunosuppressants, Live vaccines

Disqualifiers: Uveal melanoma, CNS metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining new study vaccines, IO102/IO103 (a PD-L1/IDO peptide vaccine), with the standard drugs nivolumab and relatlimab is safe and effective for treating people with advanced melanoma that can't be surgically removed. It targets individuals with melanoma who haven't received previous systemic therapy. Participants should have at least one measurable melanoma lesion outside of bones and the brain. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on high-dose steroids or other immunosuppressive drugs within 14 days of starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining IO102/IO103 with nivolumab and relatlimab yields promising safety results. In studies involving patients new to anti-PD-1 therapy, this combination was generally well-tolerated. Common side effects included tiredness, mild skin reactions, and nausea, but these were usually manageable. Serious side effects were rare.

Nivolumab and relatlimab have already been approved for other uses, so their safety has been studied extensively, and their side effects are well known. While IO102/IO103 is still under investigation, early safety data are encouraging. Prospective participants should consult a healthcare provider about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IO102/IO103 combined with Nivolumab-Relatlimab for melanoma because it offers a fresh approach by targeting the immune system in a novel way. Unlike traditional treatments like chemotherapy or single-agent immunotherapies, this combination works by using a dual-agent checkpoint blockade approach, potentially boosting the body's ability to fight cancer more effectively. IO102/IO103 specifically targets immune-suppressing mechanisms in the tumor environment, while Nivolumab-Relatlimab blocks proteins that usually help tumors evade the immune system. This multi-pronged attack could lead to improved outcomes for patients, addressing melanoma's ability to resist treatment.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research shows that combining IO102/IO103 with other drugs may help treat melanoma. In one study, 80% of patients who took IO102/IO103 with nivolumab experienced tumor shrinkage or disappearance. Additionally, 50% of these patients had a complete response, meaning their cancer became undetectable for a while.

In this trial, all participants will receive a combination treatment of IO102/IO103, nivolumab, and relatlimab. Studies have shown that combining nivolumab and relatlimab yields better results than using nivolumab alone. After four years, patients with advanced melanoma experienced longer periods without cancer progression. These findings suggest that the combination treatment could effectively fight melanoma. ^{4 6 7 8 9}

Who Is on the Research Team?

James Smithy, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with untreated, unresectable stage III or IV melanoma. Participants must have good performance status, adequate organ function, and no prior systemic therapy against their melanoma in the last 6 months. They should not have brain metastases or a history of severe allergies to study drugs. Contraception is required for those who can bear children.

Inclusion Criteria

Patient must be able to provide informed consent

Patients of childbearing potential* who are sexually active partner must use two methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product: cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control

I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

I do not have another cancer that needs treatment or affects melanoma tests.

Uncontrolled (i.e., unstable) concomitant medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety or compliance with the study procedures. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll

You are pregnant or breastfeeding, as confirmed by a recent pregnancy test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IO102/IO103 and nivolumab-relatlimab FDC. IO102/IO103 is administered on Days 1 and 15 of the first two 28-day cycles, then on Day 1 of subsequent cycles. Nivolumab-relatlimab FDC is administered on Day 1 of every 28-day cycle.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the incidence of adverse events up to 100 days after the last dose.

100 days

What Are the Treatments Tested in This Trial?

Interventions

• IO102/IO103
• Nivolumab-Relatlimab

Trial Overview The study tests if IO102/IO103 vaccines combined with nivolumab and relatlimab are safe and effective for advanced melanoma treatment. It's designed to see how well this combination works compared to standard treatments.

How Is the Trial Designed?

Group I: IO102/IO103, Nivolumab, and Relatlimab Experimental Treatment 2 Interventions

All patients will be treated with nivolumab-relatlimab FDC on Day 1 of every 28-day cycle for up to two years. Patients will be treated with IO102/IO103 on Days 1 and 15 of the first two 28-day cycles, then on Day 1 of subsequent cycles for up to two total years of treatment.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

IO Biotech

Industry Sponsor

Trials

9

Recruited

750+

Published Research Related to This Trial

In cohort A, which included 30 patients with metastatic melanoma, the combination of an IDO/PD-L1 vaccine and nivolumab resulted in an impressive overall response rate of 80%, with 50% achieving a complete response and a median progression-free survival of 25.5 months.

Cohort B, where the vaccine was added to patients already on anti-PD-1 therapy, showed limited efficacy with only stable disease in 2 out of 10 patients and a median progression-free survival of just 2.4 months, indicating that the combination may not be effective for those with progressive disease during anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. Lorentzen, CL., Kjeldsen, JW., Ehrnrooth, E., et al.[2023]

In a phase 1/2 study involving 30 patients with metastatic melanoma, the combination of the immune-modulatory vaccine (IO102/IO103) with nivolumab showed a high objective response rate of 80%, with 43% of patients achieving complete responses.

The safety profile of the combination therapy was comparable to nivolumab alone, and after a median follow-up of nearly 23 months, the median progression-free survival was 26 months, indicating promising efficacy and tolerability for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Kjeldsen, JW., Lorentzen, CL., Martinenaite, E., et al.[2023]

Nivolumab plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

Nivolumab and pembrolizumab, two anti-PD-1 antibodies, have demonstrated significant antitumor activity and acceptable safety profiles in patients with metastatic melanoma during early clinical trials.

Ongoing Phase III studies are further evaluating the efficacy and safety of anti-PD-1 therapies, including promising results from combinations with other treatments like anti-CTLA-4 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. Simeone, E., Grimaldi, AM., Ascierto, PA.[2023]

The first-in-human study of the PD-L1 peptide vaccine (IO103) in 10 patients with multiple myeloma showed low toxicity, with most adverse reactions being mild (grade 1-2) injection site reactions, indicating a favorable safety profile.

All patients demonstrated a strong immune response to the vaccine, with three out of ten showing clinical improvements, suggesting that IO103 may effectively stimulate the immune system against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Vaccination Against PD-L1 With IO103 a Novel Immune Modulatory Vaccine in Multiple Myeloma: A Phase I First-in-Human Trial. Jørgensen, NG., Klausen, U., Grauslund, JH., et al.[2021]

Nivolumab, administered at 3 mg/kg with or without a peptide vaccine, was well tolerated and demonstrated a 25% response rate in patients with advanced melanoma, regardless of prior ipilimumab treatment.

The study suggests that nivolumab can induce long-lasting responses, with some patients responding for up to 140 weeks, and highlights the potential for combining or sequencing nivolumab with ipilimumab for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. Weber, JS., Kudchadkar, RR., Yu, B., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS2701

A randomized phase 2 trial of the IO102-IO103 (IDO and ... Treatment with IO102-IO103 plus nivolumab in anti-PD-1 naïve metastatic melanoma showed 80% objective response rate including 50% complete ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8904254/

A phase 1/2 trial of an immune-modulatory vaccine against ... Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7–90.5%) was reached, with 43% (CI, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05155254

Study Details | NCT05155254 | IO102-IO103 in ... The primary objective is to investigate the efficacy of IO102-IO103 in combination with pembrolizumab (compared with pembrolizumab alone) in terms of ...

4. onclive.com onclive.com/view/io102-io103-plus-pembrolizumab-demonstrates-favorable-activity-in-pd-l1-high-hnscc-and-nsclc

IO102-IO103 Plus Pembrolizumab Demonstrates ... IO102-IO103 plus pembrolizumab produced an ORR of 48.4% in advanced NSCLC and 44.4% in HNSCC. Median PFS reached 8.1 months in NSCLC and 7.0 ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)42360-9/fulltext

A phase I/II trial At data cut-off, 45% have reached complete response and 34% partial response, which was significantly higher than a matched control group extracted from the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05912244

NCT05912244 | A Study of IO102/IO103, Nivolumab, and ... The researchers are doing this study to find out whether the study vaccines, IO102/IO103, given in combination with the standard-of-care drug combination, ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/pd-l1-ido-peptide-vaccine-io102-103?pn=1

Clinical Trials Using PD-L1/IDO Peptide Vaccine IO102-103 Trials 1-4 of 4. IO102/IO103 and Nivolumab-Relatlimab Fixed Dose Combination for the Treatment of Patients with Untreated, Unresectable Stage III/IV Melanoma.

8. jitc.bmj.com jitc.bmj.com/content/11/5/e006755

Long-term follow-up of anti-PD-1 naïve patients with ... This study reports the long-term follow-up on safety and efficacy data in anti-PD-1 therapy naïve patients with metastatic melanoma treated with ...

9. mskcc.org mskcc.org/cancer-care/clinical-trials/23-098

A Phase 2 Study of IO102/IO103, Nivolumab, and ... In this study, researchers want to see how well a cancer vaccine called IO102/IO103 works in people with inoperable melanoma.