IO102-IO103 + Pembrolizumab for Resectable Cancer

Recruiting at 14 trial locations

Overseen By Shane O'Neill Clinical Program Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: IO Biotech

Must be taking: Antiretrovirals, Hepatitis B antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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: 9

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for certain resectable cancers, including Stage III melanoma and some head and neck cancers. Researchers aim to determine if a combination of two drugs, IO102-IO103 (an experimental treatment) and pembrolizumab (KEYTRUDA®), can reduce tumors and improve patient outcomes before and after surgery. Participants must have these specific types of cancer and be prepared for surgery to remove the tumors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the trial treatments.

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

Research shows that the combination of IO102-IO103 and pembrolizumab is promising in terms of safety. Studies have found that patients generally tolerate this treatment well. In trials with advanced melanoma and head and neck cancers, the combination did not cause unexpected safety issues, indicating that patients can usually handle the treatment without major side effects.

Pembrolizumab, one of the drugs in this combination, is already approved for other cancers, so its safety profile is well understood. Doctors have used it for some time and know how it works. The current trial is in an early stage, so researchers are still testing it for safety and effectiveness.

Overall, the available data suggests that the treatment is safe for patients in the trial. However, like any clinical trial, some risks may exist, and discussing these with the trial team before joining is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of IO102-IO103 and Pembrolizumab for treating resectable Stage III melanoma and advanced squamous cell carcinoma of the head and neck (SCCHN) because it offers a unique approach. Most treatments for these cancers focus on targeting specific cancer cell pathways, but IO102-IO103 works differently by aiming to enhance the body's immune response to fight cancer more effectively. This combination pairs IO102-IO103, which is delivered subcutaneously, with Pembrolizumab, an established immunotherapy given intravenously, potentially providing a more comprehensive attack on cancer cells. The dual approach could lead to improved outcomes compared to using Pembrolizumab alone, which is the current standard for some cases.

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

Research shows that combining IO102-IO103 with pembrolizumab may be promising for treating certain cancers. In this trial, participants with resectable Stage III melanoma will receive either the combination of IO102-IO103 and pembrolizumab or pembrolizumab alone. Previous studies in advanced melanoma have shown that this combination increased the time patients lived without the cancer worsening to 19.4 months, compared to 11.0 months with pembrolizumab alone. Participants with resectable locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) will receive the combination of IO102-IO103 and pembrolizumab. Early results in head and neck cancer are positive, especially in cases with high levels of PD-L1, a protein that helps the immune system identify and attack cancer cells. These findings suggest that IO102-IO103 might enhance the effectiveness of pembrolizumab in fighting these cancers. Overall, these results offer hope for patients with tumors that can be surgically removed. ^{5 6 7 8 9}

Who Is on the Research Team?

Barbara Burtness, MD

Principal Investigator

Yale New Haven Hospital - Yale Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of resectable tumors, including oral squamous cell carcinoma and melanoma. Participants must be willing to provide tissue samples, undergo tumor biopsies and imaging tests, have a performance status score of 0 or 1 (which indicates they are fully active or restricted in physically strenuous activity but ambulatory), and have not undergone previous treatments for these conditions.

Inclusion Criteria

My recent tests show my organs are working well.

My cancer is in the mouth, throat, or voice box and can be surgically removed.

You possess measurable disease characteristics according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive IO102-IO103 and pembrolizumab KEYTRUDA® as neoadjuvant treatment for 2-3 cycles

6-9 weeks

3 visits (in-person)

Surgery

Surgical resection is performed 1 to 3 weeks after the last dose of neoadjuvant treatment

1-3 weeks

Post-surgery Treatment

Participants receive post-surgery treatment with IO102-IO103 and pembrolizumab KEYTRUDA® for a total of 15 cycles

45 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 6 and 12 months after end-of-treatment visit

Long-term Follow-up

Long-term follow-up for overall survival conducted every 6 months for at least a further 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• IO102-IO103
• Pembrolizumab

Trial Overview The trial is testing IO102-IO103 combined with pembrolizumab as both pre-surgery (neoadjuvant) and post-surgery (adjuvant) treatment. It aims to assess the anti-tumor effects, safety profile, and how this combination influences immune cells within the tumors across multiple centers.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 2 Interventions

Cutaneous resectable Stage III melanoma. Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus intravenous Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B) Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B)

Group II: Cohort B - SCCHN Experimental Treatment 2 Interventions

Stage III or IVA resectable locoregionally advanced Squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx (HPV-negative), hypopharynx, or larynx Neoadjuvant Treatment (2-3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.

Group III: Cohort A - Melanoma Experimental Treatment 2 Interventions

Cutaneous resectable Stage III melanoma. Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W. Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.

Who Is Running the Clinical Trial?

IO Biotech

Lead Sponsor

Trials

9

Recruited

750+

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

Almac

Industry Sponsor

Trials

4

Recruited

490+

Theradex

Industry Sponsor

Trials

34

Recruited

1,600+

Almac

Collaborator

Trials

4

Recruited

490+

Published Research Related to This Trial

A 70-year-old woman developed immune checkpoint inhibitor (ICI)-related myocarditis and new-onset myasthenia gravis (MG) after starting pembrolizumab for metastatic thymic cancer, highlighting potential serious side effects of this treatment.

Despite the adverse effects, the patient showed significant improvement in her metastatic disease after 6 weeks, indicating that pembrolizumab can be effective in reducing tumor burden even in the presence of severe immune-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Szuchan, C., Elson, L., Alley, E., et al.[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]

The Trial Reporting in Immuno-Oncology (TRIO) recommendations were developed by a diverse group of experts to enhance the reporting of clinical trials for immuno-oncology treatments, focusing on their unique efficacy and toxicity profiles.

These recommendations aim to provide clearer evidence on the benefits and risks of immuno-oncology therapies, acknowledging that they will need to be updated regularly as the field evolves and more data becomes available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): an American society of clinical oncology-society for immunotherapy of cancer statement. Tsimberidou, AM., Levit, LA., Schilsky, RL., et al.[2019]

Pembrolizumab, an immune-checkpoint inhibitor, has shown the ability to achieve pathological complete response (CR) in a patient with microsatellite instability-high (MSI-H) colorectal cancer, marking a significant milestone in confirming its efficacy beyond clinical response.

In this case, a 45-year-old man with advanced colon cancer underwent 20 courses of pembrolizumab treatment, leading to no residual tumor cells after surgery, highlighting the importance of accurate diagnosis and monitoring for effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability. Tominaga, T., Nonaka, T., Fukuda, A., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

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]

In a study of 243 patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, there was no significant difference in overall survival between those treated with pembrolizumab alone (IO-mono) and those receiving it in combination with chemotherapy (CT-IO), suggesting that avoiding chemotherapy does not negatively impact survival outcomes.

Younger patients and those with more severe symptoms or brain metastases were more likely to receive the combination treatment, but factors like male gender and poor performance status were identified as negative predictors for overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50. Pons-Tostivint, E., Hulo, P., Guardiolle, V., et al.[2023]

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]

The Trial Reporting in Immuno-Oncology (TRIO) recommendations were developed by a diverse group of experts to enhance the reporting standards for clinical trials involving immuno-oncology treatments, focusing on their unique efficacy and toxicity profiles.

These recommendations aim to provide clearer evidence on the benefits and risks of immuno-oncology therapies, acknowledging that the field is rapidly evolving and will require ongoing updates to stay relevant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement. Tsimberidou, AM., Levit, LA., Schilsky, RL., et al.[2020]

Pembrolizumab (Keytruda) has been approved for treating metastatic microsatellite instability-high colorectal cancer (CRC), showing promising efficacy in a small phase 2 clinical trial, which highlights the potential of immunotherapy in this cancer type.

Microsatellite instability-high CRCs that express PD-L1 are more likely to respond to PD-1/PD-L1 checkpoint inhibitors, while microsatellite-stable tumors show much less response, indicating the importance of PD-1/PD-L1 testing in guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer. Marginean, EC., Melosky, B.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-squamous-cell-carcinoma-of-head-and-neck-4-2022-99bf3

IO102-IO103 + Pembrolizumab for Resectable Cancer This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune infiltration of IO102-IO103 in combination with pembrolizumab ...

2. bcan.org bcan.org/clinicaltrials/io102-io103-in-combination-with-pembrolizumab-as-first-line-treatment-for-patients-with-metastatic-nsclc-scchn-or-mubc/

IO102-IO103 in Combination With Pembrolizumab as First- ... A Phase II Multi-Arm (Basket) Trial Investigating the Safety and Efficacy of IO102-IO103 in Combination With Pembrolizumab, as First-Line Treatment for Patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05280314

NCT05280314 | Phase II Trial of Neoadjuvant and ... This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune infiltration of IO102-IO103 in combination with pembrolizumab ...

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

5. investors.iobiotech.com investors.iobiotech.com/news-events/news/news-details/2024/IO-Biotech-Announces-Positive-Results-from-Phase-2-Trial-of-IO102-IO103-in-the-First-line-Treatment-of-Advanced-Head-and-Neck-Cancer/default.aspx

IO Biotech Announces Positive Results from Phase 2 Trial ... IO Biotech announces positive results from Phase 2 trial of IO102-IO103 in the first-line treatment of advanced head and neck cancer.

6. 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 ...

7. 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 ...

8. 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 ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02600-0/fulltext

1022P A phase II trial of the IO102-IO103 vaccine plus ... IO102-IO103/pembrolizumab shows encouraging clinical activity for 1L treatment of PD-L1 high SCCHN. The combination is tolerable, with no unexpected safety ...