Pembrolizumab + IO102-103 for Head and Neck Cancer

(KIEO Trial)

Recruiting at 5 trial locations

Overseen By Tanguy Seiwert, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Pregnancy, Active infection, Autoimmune, 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: 6

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, Pembrolizumab (an immunotherapy drug) and IO102-103 (an experimental treatment), to determine their safety and effectiveness for individuals with surgically removable head and neck cancer. Researchers aim to assess whether these drugs can be administered safely before surgery and if they cause any delays to the planned procedure. The trial seeks participants with operable head and neck cancer who have not previously received treatments such as chemotherapy or radiation. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have received certain cancer treatments recently, you may need to discuss this with the trial team.

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

Research has shown that the combination of IO102-103 and pembrolizumab is generally safe for patients. In earlier studies involving individuals with advanced head and neck cancer, this combination proved effective and did not present any unexpected safety issues. Patients tolerated the treatment well, and no new or unusual side effects emerged. While all medications can have side effects, current data suggest that this combination does not raise any surprising safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about the combination of Pembrolizumab and IO102-103 for head and neck cancer because it offers a fresh approach to tackling the disease. Pembrolizumab, an immunotherapy, helps activate the immune system to attack cancer cells, while IO102-103 is designed to target and inhibit specific immune-suppressing mechanisms within the tumor environment. This dual-action strategy could potentially enhance the effectiveness of treatment compared to standard therapies like chemotherapy or radiotherapy, which don't specifically enhance immune response. By blocking the cancer's defenses and boosting the body's natural immune response, this combination aims to offer a more targeted and potentially more effective treatment option.

What evidence suggests that this treatment might be an effective treatment for head and neck cancer?

Research has shown that combining IO102-103 with pembrolizumab holds promise for treating cancer. In earlier studies, this combination extended the time without cancer progression in patients with advanced melanoma. It also proved effective for patients with head and neck cancer and other solid tumors. This trial will specifically evaluate the combination of IO102-103 and pembrolizumab for head and neck cancer, offering hope for improved outcomes. The evidence supports its potential to slow cancer progression. ^{1 2 3 4 6}

Who Is on the Research Team?

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with resectable head and neck squamous cell carcinoma who can consent to treatment and surgery. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have no severe heart conditions, active infections, recent cancer treatments or live vaccines. Those with certain other cancers or autoimmune diseases are excluded.

Inclusion Criteria

Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

My cancer is at a stage that can be removed with surgery.

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

Exclusion Criteria

Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as per assessment of the treating physician. Chronic managed disorders that are not clinically active are acceptable

Women of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to treatment allocation/registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant Pembrolizumab and IO102-103 prior to surgery

6 weeks

Weekly visits for subcutaneous injections

Surgical Resection

Participants undergo surgical resection after neoadjuvant therapy

1 week

Adjuvant Treatment

Participants receive adjuvant Pembrolizumab and IO102-103 post-surgery

48 weeks

Every 6 weeks for Pembrolizumab, every 3 to 6 weeks for IO102-103

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

What Are the Treatments Tested in This Trial?

Interventions

• IO102-103
• Pembrolizumab

Trial Overview

The safety of combining Pembrolizumab and IO102-103 before surgery in patients with head and neck squamous cell carcinoma is being tested. The goal is to monitor side effects closely and ensure there's no delay in the scheduled surgery due to these investigational drugs.

How Is the Trial Designed?

Group I: Single Cohort Experimental Treatment 2 Interventions

Neoadjuvant Pembrolizumab ( 400mg IV infusion x1) + IO102-103 ( Subcutaneous injection weekly x6) Adjuvant Pembrolizumab ( 400 mg IV infusion Every 6 weeks x8) + IO102-103 ( Subcutaneous injection every 3 week x6 then every 6 weeks x5)

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

IO Biotech

Industry 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

Published Research Related to This Trial

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

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]

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy showed overall survival outcomes similar to those in randomized control trials, indicating the effectiveness of immunotherapy in real-world settings.

Factors such as worse performance status (ECOG-PS) and higher absolute lymphocyte count (ALC) were significant predictors of overall survival, with lower performance status correlating with poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of real-world outcomes following immunotherapy in recurrent or metastatic head and neck squamous cell carcinoma with outcomes of randomized controlled trials. Yalamanchali, A., Yang, K., Roof, L., et al.[2023]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., 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]

In a study of 257 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab, biomarkers such as tumor mutational burden (TMB), PD-L1 expression, and T-cell-inflamed gene expression profile (Tcellinf GEP) were found to be significantly associated with overall response rates (ORR) to the treatment.

The study indicated that higher levels of these biomarkers correlated with better treatment responses, suggesting that they could be useful in predicting how well patients will respond to pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers predictive of response to pembrolizumab in head and neck cancer. Pfister, DG., Haddad, RI., Worden, FP., et al.[2023]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., 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]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Citations

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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 ...

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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 cancer vaccine plus pembrolizumab for first-line (1L) treatment of advanced solid tumors: final results of a phase 2 basket trial.

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lungcancerstoday.com

lungcancerstoday.com/post/combining-the-io102-io103-cancer-vaccine-with-pembrolizumab-dr-riess-shares-insights-on-nsclc-outcomes-from-a-phase-2-basket-trial

ESMO 2025: Combining the IO102-IO103 Cancer Vaccine ...

In terms of this phase 2 basket trial of IO102-IO103 and pembrolizumab, the patients had advanced metastatic head and neck squamous cell ...

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annalsofoncology.org

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

1022P A phase II trial of the IO102-IO103 vaccine plus ...

Combination of IO102-IO103/nivolumab in a phase 1/2 trial of anti-PD-1 naïve metastatic melanoma patients (pts) showed 80% ORR (50% complete response); was well ...

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cancernetwork.com

cancernetwork.com/view/cancer-vaccine-pembrolizumab-improves-pfs-in-treatment-naive-melanoma

Cancer Vaccine/Pembrolizumab Improves PFS in ...

A novel cancer vaccine, IO102-IO103, combined with pembrolizumab, showed promising results in improving PFS for advanced melanoma.

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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.