CIMAvax Vaccine + Nivolumab + Pembrolizumab for Non-small Cell Lung Cancer and Squamous Head and Neck Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Roswell Park Cancer Institute
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a combination of a cancer vaccine (CIMAvax) and immune-boosting drugs (nivolumab and pembrolizumab). CIMAvax has shown promising results in lung cancer patients, while nivolumab and pembrolizumab have significantly improved overall survival in various cancers. It targets patients with advanced lung and head/neck cancers that have spread. The treatment works by enhancing the immune system's ability to fight cancer.
Is the CIMAvax Vaccine combined with the drugs Nivolumab and Pembrolizumab a promising treatment for non-small cell lung cancer and squamous head and neck cancer?Yes, the combination of CIMAvax Vaccine with the drugs Nivolumab and Pembrolizumab is promising. Nivolumab and Pembrolizumab are known to boost the immune system to fight cancer, and the CIMAvax Vaccine may enhance their effectiveness. This combination has shown potential in improving survival rates for certain cancers.23579
What safety data exists for the combination of CIMAvax, Nivolumab, and Pembrolizumab in treating cancer?The safety data for Nivolumab and Pembrolizumab, both anti-PD-1 monoclonal antibodies, indicate they are associated with distinct immune-related adverse effects. A systematic review and meta-analysis of randomized clinical trials have summarized the toxicity profiles of these agents. Additionally, a phase II trial of Pembrolizumab in non-small cell lung cancer reported interim safety results. However, specific safety data for the combination with CIMAvax is not detailed in the provided research.1481012
What data supports the idea that CIMAvax Vaccine + Nivolumab + Pembrolizumab for Non-small Cell Lung Cancer and Squamous Head and Neck Cancer is an effective treatment?The available research shows that treatments involving nivolumab and pembrolizumab, which are part of the combination with CIMAvax Vaccine, have shown promising results in treating head and neck squamous cell carcinoma. For example, a systematic review found that these drugs had a favorable response rate of about 45.9% in patients with head and neck cancer, with no unexpected severe side effects. This suggests that the combination treatment could be effective for these types of cancers.3671113
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received anticancer chemotherapy within 4 weeks before the first administration of the study drug, and you should not be on systemic corticosteroids or immunosuppressive drugs within 4 weeks prior to starting the study drug, unless they are for hormone replacement or short-course supportive medication. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
This trial is for adults with advanced non-small cell lung cancer or squamous head and neck cancer. Participants must have a life expectancy of at least 6 months, normal organ function, no recent chemotherapy, untreated brain metastases, or major surgery. They should not be pregnant and agree to use contraception. Those with certain autoimmune diseases or previous immunotherapy (with some exceptions) are excluded.Inclusion Criteria
I can perform all self-care but may not be able to do heavy physical work.
My kidney function, measured by creatinine or GFR, is within the normal range.
Exclusion Criteria
I haven't had major surgery or recovered from one in the last 2 weeks.
I have had myocarditis before.
I have a history of irregular heartbeats from the lower chambers of my heart.
My tumor has a mutation treatable by FDA-approved drugs, but I haven't received them yet.
I do not have any serious infections or uncontrolled medical conditions.
I have a condition that weakens my immune system, like HIV.
My cancer has spread to the lining of my brain and spinal cord.
Treatment Details
The trial is testing the CIMAvax vaccine combined with nivolumab or pembrolizumab to see if they can slow down tumor growth in patients better than current treatments. It's a phase I/II study which means it's looking at the best dose and side effects as well as how effective this combination could be.
4Treatment groups
Experimental Treatment
Group I: Phase II Study D (CIMAvax, pembrolizumab)Experimental Treatment3 Interventions
PHASE II STUDY D: Patients with PD-L1 expression \< 50% after 4 cycles of induction chemotherapy with pembrolizumab, receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Group II: Phase II Study C, D & E (CIMAvax, pembrolizumab)Experimental Treatment3 Interventions
PHASE II STUDY C, D \& E: Patients with PD-L1 expression \>= 50% receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for pembrolizumab repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Group III: Phase II Study A and B (CIMAvax, nivolumab)Experimental Treatment3 Interventions
PHASE II STUDY A and B: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for nivolumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients in Study A with antibody titer \>= 1:4000 at the end of the loading phase may receive CIMAvax IM every 8 or 12 weeks during the maintenance phase.
Group IV: Phase I (CIMAvax, nivolumab)Experimental Treatment3 Interventions
LOADING PHASE I: Patients receive CIMAvax IM and nivolumab IV over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.
MAINTENANCE PHASE I: Patients who do not experience a DLT receive CIMAvax every 4 weeks and nivolumab every 2 weeks.
Find a clinic near you
Research locations nearbySelect from list below to view details:
St. Francis HospitalRoslyn, NY
Roswell Park Cancer InstituteBuffalo, NY
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN
Good Samaritan HospitalWest Islip, NY
More Trial Locations
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Who is running the clinical trial?
Roswell Park Cancer InstituteLead Sponsor
References
Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [2022]Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents.
Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. [2022]Targeted immunotherapy has become the most promising approach for tumor patients. Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, can reverse immune suppression and release T cell activation. Nivolumab, a fully human immunoglobulin G4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and promotes antitumor immunity, and it is effective for treating non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC) and other cancers. The present review summarizes the efficacy and current status of clinical trials of nivolumab and that enabled nivolumab to be investigated in patients.
Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. [2022]Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK).
Influenza vaccination in patients with lung cancer receiving anti-programmed death receptor 1 immunotherapy does not induce immune-related adverse events. [2019]Influenza vaccination is recommended in patients with cancer to reduce influenza-related complications. Recently, more immune-related adverse events (irAEs) were demonstrated in patients with lung cancer who were vaccinated with the trivalent seasonal influenza vaccine during anti-programmed death receptor 1 (PD-1) immunotherapy. Confirmation of these findings is essential before recommendations on influenza vaccination may be revoked.
Vaccine Increases PFS for Metastatic Tumors. [2020]A vaccine that targets tumor neoantigens may improve the effectiveness of nivolumab. A trial that included patients with metastatic melanoma, non-small cell lung cancer, and bladder cancer found that progression-free survival was longer than in historical controls. The vaccine also stimulated tumor-specific T cells.
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.
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.
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.
Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. [2021]Nivolumab and pembrolizumab are approved for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Physicians and patients are uncertain which drug is preferable, rendering a cost-effectiveness comparison between them necessary.
Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. [2021]There is a concern that influenza vaccination may increase the incidence of immune-related adverse events in patients receiving immune checkpoint inhibitors (ICIs). The aim of this systematic review was to summarize the available data on the safety and efficacy of influenza vaccination in cancer patients receiving ICIs.
Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]Given the recent successes of anti-PD-1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD-1/PD-L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and clinicaltrials.gov were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 ± 5.7% with a 41.5 ± 5.6% single agent mean ORR. There were no deaths due to immune-related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune-related toxicities in phase I/II clinical trials.
Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors. [2023]Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood.
Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC).