Ramucirumab + Pembrolizumab for Head and Neck Cancer (Rambro2 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Washington University School of Medicine
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This is a phase 2 study investigating the efficacy of ramucirumab in combination with pembrolizumab compared to pembrolizumab monotherapy. Ramucirumab is a VEGFR-2 inhibitor believed to potentially enhance the efficacy of PD-1 inhibitors such as pembrolizumab.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids, intense immunosuppressive therapy, or chronic antiplatelet therapy, you may need to adjust or stop these before starting the trial.
What data supports the effectiveness of the drug combination of Ramucirumab and Pembrolizumab for head and neck cancer?
Research shows that Pembrolizumab, one of the drugs in the combination, has been effective in treating head and neck cancer, especially in patients with high levels of PD-L1, a protein that can affect the immune system's ability to fight cancer. It has shown good tumor response and manageable side effects in several studies.
12345Is the combination of Ramucirumab and Pembrolizumab safe for humans?
Pembrolizumab has been studied for head and neck cancer, showing some serious side effects like pneumonia, breathing problems, confusion, and immune system-related issues like inflammation of the lungs, liver, and thyroid problems. The safety of Ramucirumab in combination with Pembrolizumab specifically hasn't been detailed, but Pembrolizumab alone has a manageable safety profile in the context of head and neck cancer.
36789How is the drug combination of Ramucirumab and Pembrolizumab unique for treating head and neck cancer?
The combination of Ramucirumab and Pembrolizumab is unique because it pairs an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells with another drug (Ramucirumab) that targets blood vessels feeding the tumor, potentially enhancing the overall anti-cancer effect.
1261011Eligibility Criteria
Adults with PD-L1 positive head and neck squamous-cell carcinoma, who haven't had systemic therapy for recurrent/metastatic cancer. They must have measurable disease, be in good physical condition (ECOG 0-1), have normal organ/blood function, agree to use contraception, and not be pregnant or breastfeeding. Excluded are those with negative PD-L1 status, recent surgeries or significant bleeding events, other cancers within a year (except certain skin cancers), serious illnesses or uncontrolled hypertension.Inclusion Criteria
My head or neck cancer cannot be cured with surgery or radiation.
My cancer is PD-L1 positive.
My cancer can be measured by scans or physical exam.
I am 18 years old or older.
I am fully active or can carry out light work.
My liver enzymes are within the required range.
I agree to use birth control during and up to 28 days after the study.
Exclusion Criteria
My cancer does not show PD-L1 based on a specific test.
My cancer is in the skin or nasopharynx.
I haven't had major surgery in the last 4 weeks or minor surgery in the last week.
I have received radiation to ease symptoms within the last 2 weeks.
I haven't had any serious wounds, ulcers, or bone fractures in the last 28 days.
My liver disease is severe, with complications like swelling or confusion.
I haven't had any serious illnesses or conditions in the last 3 months that would stop me from following the study's requirements.
I have not had a GI perforation or fistula in the last 6 months.
I have a history of inflammatory bowel disease, such as ulcerative colitis or Crohn's disease.
I haven't had a heart attack, stroke, or major blood clot in the past 6 months.
I have not had severe bleeding in the last 3 months.
I am on daily medication for blood thinning, but only take aspirin up to 325 mg/day.
I haven't had any recent bleeding or conditions that increase my risk of bleeding.
Participant Groups
The trial is testing the combination of Ramucirumab (a VEGFR-2 inhibitor) and Pembrolizumab versus Pembrolizumab alone in treating patients. It's a phase 2 study aimed at seeing if adding Ramucirumab can boost the effectiveness of Pembrolizumab in this type of cancer.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm 1: Ramucirumab and PembrolizumabExperimental Treatment2 Interventions
Patients receive ramucirumab IV and pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.
Group II: Arm 2: Pembrolizumab monotherapyActive Control1 Intervention
Patients receive pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.
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:
Washington University School of MedicineSaint Louis, MO
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Who is running the clinical trial?
Washington University School of MedicineLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
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).
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 methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. [2019]There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma.
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 With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. [2023]Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.
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.
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.
Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities.
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.
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.
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).