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

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Prantesh Jain, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

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.

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.

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. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{3 5 11 12 13}

Research Team

Prantesh Jain, MD

Principal Investigator

Roswell Park Cancer Institute

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

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

Treatment Details

Interventions

• CIMAvax Vaccine (Cancer Vaccine)
• Nivolumab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

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.

Participant Groups

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

St. Francis Hospital Roslyn, NY

Roswell Park Cancer Institute Buffalo, NY

Indiana University Melvin and Bren Simon Comprehensive Cancer Center Indianapolis, IN

Good Samaritan Hospital West Islip, NY

More Trial Locations

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Patients Recruited

40,500+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine Increases PFS for Metastatic Tumors. [2020]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]

2. England 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. [2021]

3. England 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. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

5. United States 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. [2022]

6. England 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. [2023]

7. England 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. [2019]

8. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

9. United States 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Influenza vaccination in cancer patients receiving immune checkpoint inhibitors: A systematic review. [2021]

11. United States 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Vaccine Increases PFS for Metastatic Tumors. [2020]

13. Australia pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. [2022]