Pembrolizumab + IO102-103 for Head and Neck Cancer

(KIEO Trial)

Recruiting at 4 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

Trial Summary

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.

What data supports the effectiveness of the drug pembrolizumab for head and neck cancer?

Pembrolizumab has been approved by the FDA for treating head and neck cancer that has returned or spread after chemotherapy, based on its ability to shrink tumors in some patients and maintain this effect for several months. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and IO102-103 safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been used in various cancers and is generally considered safe, but it can cause serious side effects like pneumonia, liver inflammation, and thyroid problems. These side effects are related to its role as an immune checkpoint inhibitor, which can sometimes cause the immune system to attack healthy cells. ^{1 3 6 7 8}

How does the drug Pembrolizumab + IO102-103 differ from other treatments for head and neck cancer?

Pembrolizumab is a drug that works by blocking a pathway that cancer cells use to hide from the immune system, and it is already used for certain head and neck cancers. The combination with IO102-103 is unique because it may enhance the immune response against cancer cells, potentially offering a new approach for patients who have not responded well to other treatments. ^{1 3 4 9 10}

What is the purpose of this trial?

This research is being done to see if it is safe to give investigational combination of study drugs (Pembrolizumab and IO102-103) before surgery to people with surgically resectable (removable) newly diagnosed or recurrent metastatic SCCHN. This will be done by watching participants closely for possible side effects from Pembrolizumab and IO102-103. In addition, participants will be monitored for any delays to their surgery due to the study drugs.

Research Team

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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, 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 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]

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]

References

1. England 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. [2019]

2. United States 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. [2023]

3. United States 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. [2023]

4. England 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. [2023]

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

Biomarkers predictive of response to pembrolizumab in head and neck cancer. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

9. United States 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. [2022]

10. Switzerland 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. [2022]