IO102/IO103 + Nivolumab-Relatlimab for Melanoma

Recruiting at 8 trial locations

Overseen by James Smithy, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Steroids, Immunosuppressants, Live vaccines

Disqualifiers: Uveal melanoma, CNS metastases, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing new vaccines combined with two existing drugs to treat people with melanoma that can't be surgically removed and who haven't received any treatment yet. The vaccines aim to help the body recognize and attack cancer cells, while the drugs enhance the immune system's ability to fight the cancer. One of the drugs has been shown to greatly improve survival in widespread, inoperable malignant melanoma.

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.

What data supports the effectiveness of the treatment IO102/IO103 + Nivolumab-Relatlimab for melanoma?

In a study with 30 patients who had not previously received anti-PD1 therapy, the combination of the IO102/IO103 vaccine and nivolumab showed an objective response rate of 80%, with 43% achieving complete responses. The median progression-free survival was 26 months, indicating promising effectiveness for this treatment in metastatic melanoma. ^{1 2 3 4 5}

Is the combination of IO102/IO103 and Nivolumab-Relatlimab safe for humans?

The combination of IO102/IO103 and Nivolumab has shown a safety profile comparable to Nivolumab alone in patients with metastatic melanoma, suggesting it is generally safe for humans. ^{1 2 3 4 5}

What makes the IO102/IO103 + Nivolumab-Relatlimab treatment unique for melanoma?

This treatment combines a novel vaccine (IO102/IO103) targeting IDO and PD-L1, which are proteins that help cancer cells evade the immune system, with the immunotherapy drugs nivolumab and relatlimab. This combination aims to enhance the immune response against melanoma by targeting multiple immune checkpoints, potentially improving outcomes for patients who do not respond to standard anti-PD-1 therapies. ^{1 2 3 4 6}

Research Team

James Smithy, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• IO102/IO103 (Cancer Vaccine)
• Nivolumab-Relatlimab (Checkpoint Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. England 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. [2023]

3. Switzerland 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. [2021]

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

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. [2022]

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

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. [2022]