Radiation + Immunotherapy for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
+51 other locations
Overseen byDavid J Sher
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: ECOG-ACRIN Cancer Research Group
Must be taking: Pembrolizumab, Chemotherapy
Must not be taking: Corticosteroids, Immunosuppressive drugs
Disqualifiers: Autoimmune disease, Pregnancy, Live vaccines, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase III trial compares pembrolizumab with radiation therapy to pembrolizumab without radiation therapy (standard therapy) given after pembrolizumab plus chemotherapy for the treatment of patients with squamous cell carcinoma of the head and neck that has spread from where it first started (primary site) to other places in the body (metastatic). Pembrolizumab is a type of immunotherapy that stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells. Radiation therapy uses high-powered rays to kill cancer cells. Giving radiation with pembrolizumab may be more effective at treating patients with metastatic head and neck cancer than the standard therapy of giving pembrolizumab alone.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you have an active autoimmune disease requiring systemic treatment, you may not be eligible. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment for head and neck cancer?
Research shows that pembrolizumab, when used with radiation therapy, can improve survival in patients with head and neck cancer, especially those with high levels of PD-L1, a protein that helps cancer cells hide from the immune system. Additionally, combining pembrolizumab with radiation has been shown to be safe and feasible, potentially enhancing the immune response against tumors.
12345Is the combination of radiation and pembrolizumab safe for treating head and neck cancer?
Pembrolizumab, when used for head and neck cancer, has been found to be generally safe, but it can cause serious side effects like pneumonia, breathing difficulties, confusion, and immune system-related issues such as inflammation of the lungs, liver, and intestines. Combining pembrolizumab with radiation therapy has been shown to be safe and feasible in early studies for locally advanced head and neck cancer.
13678How is the drug pembrolizumab unique for treating head and neck cancer?
Pembrolizumab is unique because it is an immune checkpoint inhibitor that helps the immune system attack cancer cells by blocking a specific pathway (PD-1/PD-L1) that tumors use to hide from immune cells. This is different from traditional chemotherapy, which directly kills cancer cells but often with more side effects.
13689Eligibility Criteria
This trial is for adults with metastatic squamous cell carcinoma of the head and neck. Participants must be in good physical condition, have measurable disease, and not have had prior head and neck radiotherapy. They should not be pregnant or breastfeeding, must agree to use contraception, and cannot have an active autoimmune disease requiring recent systemic treatment.Inclusion Criteria
Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive measures for 4 months after the last dose of protocol treatment and must not breastfeed while on study treatment through 4 months after the last dose of protocol treatment
You have enough infection-fighting white blood cells.
You have a high level of white blood cells in your body.
+24 more
Exclusion Criteria
I haven't needed treatment for an autoimmune disease in the last 2 years.
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
I haven't had any live vaccines in the last 30 days.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Initial Systemic Therapy
Patients receive pembrolizumab with chemotherapy (carboplatin and paclitaxel, or cisplatin and fluorouracil, or carboplatin and fluorouracil)
21 weeks
Regular visits for chemotherapy administration
Randomization and Treatment
Patients are randomized to receive either pembrolizumab with radiation therapy or pembrolizumab monotherapy
Varies based on treatment arm
Regular visits for pembrolizumab and radiation therapy administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 3 years
Periodic visits for imaging and assessments
Participant Groups
The study compares two approaches: pembrolizumab combined with radiation therapy versus standard therapy (pembrolizumab alone) after initial chemoimmunotherapy. The goal is to see if adding radiation improves outcomes for patients with this type of cancer that has spread from its original site.
4Treatment groups
Experimental Treatment
Active Control
Group I: Arm T (pembrolizumab, chemotherapy)Experimental Treatment5 Interventions
Patients receive pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV and fluorouracil IV on study.
Group II: Arm A (pembrolizumab and radiation)Experimental Treatment10 Interventions
Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV with radiation therapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Group III: Arm S (no intervention)Active Control1 Intervention
Patients proceed directly to Step II.
Group IV: Arm B (pembrolizumab monotherapy)Active Control9 Interventions
Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV monotherapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer Center-International PlazaTampa, FL
Moffitt Cancer Center - McKinley CampusTampa, FL
Moffitt Cancer CenterTampa, FL
Emory University Hospital MidtownAtlanta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
ECOG-ACRIN Cancer Research GroupLead Sponsor
National Cancer Institute (NCI)Collaborator
References
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).
Pembro Ups Survival in PD-L1-positive HNSCC. [2019]In a phase III trial, first-line treatment with single-agent pembrolizumab led to deep and durable responses among patients with head and neck tumors that expressed high levels of PD-L1.
Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov).
Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.
Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date. [2020]Relapsed and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a heterogeneous disease previously associated with poor prognosis and limited treatment options until the advent and implementation of immune checkpoint inhibitors (ICIs). The fully humanized monoclonal antibody pembrolizumab alone, or in combination with chemotherapy, was shown to have significantly improved overall survival (OS) when compared to the standard of care (SOC) EXTREME regimen consisting of the monoclonal antibody cetuximab combined with a platinum and 5-fluorouracil. Pembrolizumab with or without chemotherapy will soon supplant the EXTREME regimen that has been in use for over a decade. Given the fast-approaching significant change in the treatment algorithm for R/M HNSCC and the novelty of ICIs in general, it is important to review the literature to date to understand how this rapidly growing treatment class has come about and explore potential areas of research for the plethora of questions that remain unanswered in selecting patients appropriate for treatment with ICIs in the R/M setting. In this review, we explore the landmark trials leading to the use of ICIs for R/M HNSCC with a particular focus on pembrolizumab, the most well-studied ICI in this setting. We also provide an overview of the rationale behind the use of ICIs in relation to the immune system and challenges surrounding tumor heterogeneity and PD-L1 expression status, human papilloma virus (HPV) and the efficacy of ICI, potential of radiation therapy for enhancement of ICI response, and complications of immune-related adverse events (irAEs).
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.
Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. [2022]Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options. We aimed to assess the safety, tolerability, and antitumour activity of pembrolizumab, a humanised anti-programmed death receptor 1 (PD-1) antibody, in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck.
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.
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.