CIMAvax Vaccine + Nivolumab + Pembrolizumab for Non-small Cell Lung Cancer and Squamous Head and Neck Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active autoimmune, Brain metastasis, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a vaccine called CIMAvax works with two drugs, nivolumab and pembrolizumab, to treat certain types of cancer. It focuses on non-small cell lung cancer and squamous head and neck cancer that have spread. The goal is to find the best dose and determine if these treatments can help the immune system fight cancer more effectively. Suitable participants have advanced or recurrent non-small cell lung cancer or squamous head and neck cancer. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CIMAvax and nivolumab are being tested together to assess their safety for patients. Earlier studies have focused on determining the right dose and monitoring side effects. In these studies, CIMAvax was generally well-tolerated. Some patients experienced side effects, mostly mild, such as fatigue or skin reactions.

Nivolumab is a treatment that helps the immune system fight cancer and is already approved for certain cancers. While generally safe, nivolumab can cause side effects like tiredness, skin rash, or joint pain. More serious side effects are rare but possible.

CIMAvax is also being studied with pembrolizumab, another approved treatment similar to nivolumab. Common side effects of pembrolizumab include tiredness and nausea, with serious side effects being uncommon.

This trial is in its early stages, so researchers are still learning about the safety of combining these treatments. However, since nivolumab and pembrolizumab are already used in other cancer treatments, there is some confidence in their safety. Patients should consult their doctor to understand what these treatments might mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring a fresh approach to battling non-small cell lung cancer and squamous head and neck cancer. Unlike many conventional therapies that primarily focus on directly attacking cancer cells, CIMAvax works by targeting the epidermal growth factor (EGF), which can prevent cancer cells from growing and spreading. When combined with nivolumab or pembrolizumab, which are immune checkpoint inhibitors, this treatment aims to unleash the body's immune system against cancer more effectively. This combination might offer a more comprehensive defense, potentially leading to better outcomes for patients with these cancers.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer and squamous head and neck cancer?

Research has shown that the CIMAvax vaccine, when combined with the drug nivolumab, may help fight certain types of cancer, such as non-small cell lung cancer and squamous head and neck cancer. This trial includes a treatment arm where participants receive both CIMAvax and nivolumab. The vaccine targets a protein called epidermal growth factor (EGF), which cancer cells need to grow. In past studies, patients using CIMAvax lived longer. When combined with nivolumab, which helps the immune system attack cancer, it may be even more effective. Another arm of this trial examines the combination of CIMAvax with pembrolizumab, another immune-boosting drug that has shown promise in helping the body fight cancer. These combinations are being studied to determine if they can slow cancer growth and improve patient health. ^{1 2 3 4 6}

Who Is on the Research Team?

Prantesh Jain, MD

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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

Your platelet count is at least 100 billion per liter.

Your troponin-I level is within the normal range and your B-type natriuretic peptide (BNP) level is less than 200 pg/ml.

I agree to provide tissue and blood samples for the study.

Exclusion Criteria

I had radiotherapy or gamma knife for cancer outside the brain over 2 weeks ago and have recovered from side effects.

I haven't had major surgery or recovered from one in the last 2 weeks.

Pregnant or nursing female participants

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Loading Phase I

Patients receive CIMAvax intramuscularly and nivolumab intravenously over 60 minutes. Treatment repeats every 2 weeks for up to 4 doses.

8 weeks

4 visits (in-person)

Maintenance Phase I

Patients who do not experience a DLT receive CIMAvax every 4 weeks and nivolumab every 2 weeks.

Variable, based on patient response

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• CIMAvax Vaccine
• Nivolumab
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase II Study D (CIMAvax, pembrolizumab) Experimental Treatment 3 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 Treatment 3 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 Treatment 3 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 Treatment 3 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.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

A vaccine targeting tumor neoantigens was tested in patients with metastatic melanoma, non-small cell lung cancer, and bladder cancer, showing improved progression-free survival compared to historical controls.

The vaccine effectively stimulated tumor-specific T cells, suggesting it may enhance the effectiveness of nivolumab, a common cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine Increases PFS for Metastatic Tumors. [2020]

In a study of 127 lung cancer patients receiving nivolumab, influenza vaccination did not significantly increase the incidence of immune-related adverse events (irAEs) compared to non-vaccinated patients, with rates of 26% for vaccinated and 22% for non-vaccinated individuals.

The study found no significant differences in serious irAEs, treatment discontinuation, death, or tumor response between vaccinated and non-vaccinated groups, suggesting that influenza vaccination is safe and should be encouraged for lung cancer patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in patients with lung cancer receiving anti-programmed death receptor 1 immunotherapy does not induce immune-related adverse events. Wijn, DH., Groeneveld, GH., Vollaard, AM., et al.[2019]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Nivolumab is a PD-1 immune checkpoint inhibitor that effectively enhances antitumor immunity by blocking the PD-1 receptor on activated T cells, which helps reverse immune suppression in cancer patients.

Clinical trials have demonstrated the efficacy of nivolumab in treating various cancers, including non-small-cell lung cancer, melanoma, and renal cell carcinoma, making it a promising option in targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. Guo, L., Zhang, H., Chen, B.[2022]

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]

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors (ICIs) is safe, with no severe vaccination-related toxicities reported and a low incidence of immune-related adverse events (28.9% overall, 7.5% for grade 3-4).

The vaccination appears to be effective, as seven out of eight studies indicated positive efficacy outcomes, suggesting that it can be beneficial for this patient population, especially during the COVID-19 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. Spagnolo, F., Boutros, A., Croce, E., et al.[2021]

Neoadjuvant immunotherapy targeting the PD-1/PD-L1 axis in head and neck cancer has shown a favorable overall objective response rate of 45.9% across eight clinical trials involving 260 patients.

Importantly, there were no deaths reported due to immune-related toxicities, indicating that this treatment approach is not only effective but also safe in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. Amin, N., Maroun, CA., El Asmar, M., et al.[2022]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Pei, R., Shi, Y., Lv, S., et al.[2021]

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]

Influenza vaccination (FV) in patients with advanced thoracic cancer receiving immune checkpoint inhibitors (ICIs) is associated with a reduced severity of immune-related adverse events (IRAEs), suggesting it may be a safe option for these patients.

The study found that FV significantly decreases the risk of severe IRAEs (grade 3-5) without affecting overall survival rates, indicating that vaccination does not increase treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors. Lin, EP., Huang, LC., Whisenant, J., et al.[2023]

In a study of 34 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with PD-1 inhibitors, 29% experienced hyperprogression, where tumor growth accelerated during treatment.

Hyperprogression was significantly associated with regional recurrence, leading to shorter progression-free survival, but did not affect overall survival, highlighting the need for further research into the mechanisms behind this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Saâda-Bouzid, E., Defaucheux, C., Karabajakian, A., et al.[2022]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02955290

Study Details | NCT02955290 | CIMAvax Vaccine, ... Giving CIMAvax vaccine together with nivolumab or pembrolizumab may work better in treating patients with non-small cell lung cancer or squamous head and neck ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9382666/

Findings from a phase I trial of CIMAvax-EGF in ... The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0093775418300435

CIMAvax-EGF: Toward long-term survival of advanced ... CIMAvax-EGF is a therapeutic cancer vaccine designed to generate specific humoral response against the EGF [16], [17], [18], [19], [20]. The current CIMAvax-EGF ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-01467

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in ... This phase I/II trial studies the best dose and side effects of recombinant human EGF-rP64K/montanide ISA 51 vaccine (CIMAvax) and nivolumab or pembrolizumab

5. en.wikipedia.org en.wikipedia.org/wiki/CimaVax-EGF

CimaVax-EGF CimaVax-EGF is a vaccine used to treat cancer, specifically non-small-cell lung carcinoma (NSCLC). CIMAvax-EGF is composed of recombinant human epidermal ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04298606

A Vaccine (CIMAvax-EGF) for the Prevention of Lung ... This early phase I trial studies the side effects of a vaccine called CIMAvax-EGF and to see how well it works in preventing lung cancer from developing.