IO102-IO103 + Pembrolizumab for Advanced Melanoma

Not currently recruiting at 146 trial locations

Overseen By Anita Vedel Senior Director Clinical Operations, MSc Pharm

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: IO Biotech

Must be taking: Pembrolizumab

Disqualifiers: CNS metastases, Recent radiotherapy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 tests a new treatment for individuals with advanced melanoma, a serious type of skin cancer that cannot be surgically removed or has spread to other parts of the body. It compares the combination of an experimental drug, IO102-IO103, with an existing drug, pembrolizumab (also known as KEYTRUDA), against pembrolizumab alone to determine which is more effective in preventing cancer progression. Individuals who have not received prior treatment for their advanced melanoma and have at least one measurable tumor may be suitable candidates. The trial aims to determine if adding IO102-IO103 can improve outcomes for these patients. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients should be treatment naive, meaning they haven't had previous systemic anticancer therapy for their melanoma. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research shows that combining IO102-IO103 with pembrolizumab is generally well-tolerated. Studies have found that this combination can help patients with advanced melanoma live longer without disease progression. Although specific side effects weren't detailed, the trial's later stage suggests that earlier tests did not reveal major safety concerns. Pembrolizumab alone is already approved and widely used, providing extensive safety information. Overall, for those considering joining this trial, research indicates that the treatment's safety is promising. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma?

Unlike the standard treatment for advanced melanoma, which often includes drugs like pembrolizumab alone, the combination of IO102-IO103 and pembrolizumab brings something new to the table. IO102-IO103 is a novel therapeutic vaccine that targets specific immune system components, potentially enhancing the body's ability to fight cancer more effectively. Researchers are excited about this combination because it could boost the immune response beyond what pembrolizumab can achieve on its own, possibly leading to better outcomes for patients with advanced melanoma.

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

This trial will compare the effectiveness of combining IO102-IO103 with pembrolizumab versus using pembrolizumab alone for treating advanced melanoma. Research has shown that the combination of IO102-IO103 with pembrolizumab may extend the time patients live without disease progression by 8.4 months compared to pembrolizumab alone. Specifically, patients on the combination treatment experienced an average of 19.4 months before their disease progressed, while those on pembrolizumab alone had 11.0 months. This suggests that adding IO102-IO103 to pembrolizumab might help control the disease for a longer period. The combination has demonstrated strong results in treating advanced melanoma, offering hope for better management of the condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Inge Marie Svane, MD, Prof

Principal Investigator

Institut for Klinisk Medicin, Herlev-Gentofte Hospital; Denmark

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma that hasn't been treated before. It's open to those with a specific BRAFV600 mutation, provided they haven't had rapid disease progression or prior systemic cancer treatment for their condition. They must have at least one measurable tumor and can't have central nervous system metastases as the only active disease site.

Inclusion Criteria

My melanoma is at an advanced stage and cannot be removed with surgery.

I have at least one tumor that can be measured.

I had targeted or immune therapy over 6 months ago and didn't relapse during or within 6 months after treatment.

Exclusion Criteria

I do not have active brain metastases or my brain metastases are stable.

My cancer has a BRAFV600 mutation and is worsening quickly after standard treatment.

I had radiotherapy over 2 weeks ago and have recovered from side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years). Patients in the experimental arm also receive IO102-IO103 with an additional dose during the induction period on Day 8 of cycles 1 and 2.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with outcome measures assessed up to approximately 5.5 years.

3.5 to 5.5 years

What Are the Treatments Tested in This Trial?

Interventions

• IO102-IO103
• Pembrolizumab

Trial Overview The study compares IO102-IO103 combined with pembrolizumab against pembrolizumab alone in first-line treatment of unresectable or metastatic melanoma. Patients will receive treatments every three weeks, up to two years, aiming to see if the combination improves survival without disease progression.

How Is the Trial Designed?

Group I: IO102-IO103 + pembrolizumab Experimental Treatment 2 Interventions

IO102-IO103 subcutaneous injections (85µg) every 3 weeks for a maximum 35 cycles (up to 2 years treatment). Additional dose given during the induction period on Day 8 of cycles 1 and 2. Each patient can be treated for a maximum of 37 administrations in total (up to 2 years treatment). Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles.

Group II: pembrolizumab Active Control 1 Intervention

Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years treatment).

Who Is Running the Clinical Trial?

IO Biotech

Lead Sponsor

Trials

9

Recruited

750+

Syneos Health

Collaborator

Trials

181

Recruited

69,600+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a real-world study of 532 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 21.8 months, indicating its effectiveness outside of clinical trials.

Patients with better performance status (ECOG 0-1), normal LDH levels, and no recent corticosteroid use had significantly improved overall survival, highlighting the importance of these factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. Liu, FX., Ou, W., Diede, SJ., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Citations

1. investors.iobiotech.com investors.iobiotech.com/news-events/news/news-details/2025/IO-Biotech-Presents-Phase-3-Results-for-Cylembio-plus-KEYTRUDA-pembrolizumab-in-First-line-Advanced-Melanoma-at-ESMO-2025/default.aspx

News Details Cylembio plus pembrolizumab achieved a clinically relevant 19.4 months median progression free survival (mPFS) compared to 11.0 months mPFS ...

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

IO102-IO103 Plus Pembrolizumab Demonstrates ... Jonathan Riess, MD, discusses data for IO102-IO103 plus pembrolizumab in advanced HSNCC and NSCLC with high PD-L1 expression.

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/o102-io103-plus-pembrolizumab-improves-pfs-in-treatment-naive-advanced-melanoma

IO102-IO103 Plus Pembrolizumab Improves PFS in ... IO102-IO103 combined with pembrolizumab improved median PFS by 8.4 months in advanced melanoma patients compared to pembrolizumab alone. The ...

5. healio.com healio.com/news/hematology-oncology/20251021/vaccinepembrolizumab-combination-shows-impressive-activity-in-advanced-melanoma

Vaccine may benefit some patients with advanced melanoma Vaccine-pembrolizumab combination shows 'impressive' activity in advanced melanoma ... IO102-IO103 (IO Biotech) is an off-the-shelf, immune ...

6. investors.iobiotech.com investors.iobiotech.com/news-events/news/news-details/2025/IO-Biotech-Announces-Late-Breaking-Abstract-in-Advanced-Melanoma-Selected-for-Oral-Presentation-at-ESMO-Congress-2025/default.aspx

IO Biotech Announces Late-Breaking Abstract in Advanced ... Oral presentation will highlight the results from the randomized Phase 3 trial (IOB-013/KN-D18) of IO102-IO103 cancer vaccine plus ...