Pembrolizumab + IO102-103 for Head and Neck Cancer
(KIEO Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
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.
12345Is 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.
13678How 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.
134910Eligibility 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.
+9 more
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
+15 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Single CohortExperimental Treatment2 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Providence Cancer InstitutePortland, OR
Johns Hopkins UniversityBaltimore, MD
Sibley Memorial HospitalWashington, United States
Northwestern Memorial HospitalChicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
IO BiotechIndustry Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
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]On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
Comparison of real-world outcomes following immunotherapy in recurrent or metastatic head and neck squamous cell carcinoma with outcomes of randomized controlled trials. [2023]Evaluate outcomes of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy (IO).
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]Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS).
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]To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).
Biomarkers predictive of response to pembrolizumab in head and neck cancer. [2023]We performed an integrated biomarker evaluation in pembrolizumab-treated patients with R/M HNSCC enrolled in KEYNOTE-012 or KEYNOTE-055. The relationship between biomarkers and HPV status was explored.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.
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]Pembrolizumab and cetuximab are antibodies under investigation in head and neck squamous cell carcinoma (HNSCC) either as single agents or combined with cisplatin and other chemotherapeutic drugs, e.g., 5-fluorouracil and/or docetaxel. However, also the combination of both antibodies may have potential in recurrent/metastatic (R/M) HNSCC, in particular in cisplatin-resistant or -refractory cases or patients with comorbid disease, e.g. patients with impaired renal function.