What side effects are associated with this type of intervention?

Common treatments for NSCLC, such as PD-1 inhibitors (Nivolumab and Pembrolizumab) and EGF-targeting vaccines (like CIMAvax), have distinct side effect profiles. PD-1 inhibitors can cause immune-related adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Severe treatment-related adverse effects are less frequent with PD-1 inhibitors compared to chemotherapy, but they can still occur, such as severe pneumonitis and infusion-related reactions. EGF-targeting vaccines like CIMAvax may cause injection site reactions, flu-like symptoms, and potential allergic reactions. Overall, while these treatments are generally well-tolerated, they require careful monitoring for immune-related and other adverse effects.

What prior FDA approvals exist?

The FDA has approved several PD-1 inhibitors for the treatment of Non-Small Cell Lung Cancer (NSCLC). Pembrolizumab (Keytruda) is approved for first-line treatment of metastatic NSCLC with PD-L1 expression of 1% or more, either as monotherapy or in combination with chemotherapy. Nivolumab (Opdivo) is approved for previously treated advanced NSCLC. Atezolizumab (Tecentriq), another PD-L1 inhibitor, is approved for first-line treatment in combination with chemotherapy for metastatic NSCLC. While CIMAvax, an EGF-targeting vaccine, is still under investigation, these immunotherapies have shown significant efficacy in improving overall survival and progression-free survival in NSCLC patients.

What other types of research exist?

Promising novel alternatives for NSCLC treatment in 2024 include: 1) Cemiplimab combined with platinum-based chemotherapy, which has shown improved survival outcomes. 2) Tremelimumab and Durvalumab plus chemotherapy, which have demonstrated better overall survival and progression-free survival compared to chemotherapy alone. 3) Atezolizumab, another PD-L1 inhibitor, which has shown efficacy in patients with advanced NSCLC, particularly when combined with chemotherapy.

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Cancer Vaccine

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

Phase 1 & 2

Recruiting

Led By Grace Dy

Research Sponsored by Roswell Park Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at the time of study treatment initiation

Serum /plasma creatinine =< 1.5 x institution upper limit of normal (ULN) or estimated glomerular filtration rate (GFR) (measured or calculated with Cockcroft and Gault formula) > 45 ml/min

Must not have

Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery

History of myocarditis of any etiology

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months from 5th vaccine dose

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking healthy cells leading to inflammation in various organs, infusion-related reactions from the drug entering your body, fatigue, potential changes in blood tests that monitor liver and kidney function, and an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can perform all self-care but may not be able to do heavy physical work.

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My kidney function, measured by creatinine or GFR, is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have had myocarditis before.

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I have a history of irregular heartbeats from the lower chambers of my heart.

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My tumor has a mutation treatable by FDA-approved drugs, but I haven't received them yet.

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I do not have any serious infections or uncontrolled medical conditions.

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I have a condition that weakens my immune system, like HIV.

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My cancer has spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months from 5th vaccine dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months from 5th vaccine dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months from 5th vaccine dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting toxicity (DLT) as graded by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v. 4.03) (Phase I)

Overall survival (Phase II)

Progression-free survival (PFS) - Phase II

Secondary study objectives

Incidence of adverse events (AEs) graded according to National Cancer Institute version 4.03 (NCI CTCAE v4.03) (Phase I and II)

Overall Survival (OS)

Progression free survival (PFS) based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) (Phase II)

Other study objectives

Blood EGF levels, platelet levels, markers of immune response, and antibody functionality (Phase I and II)

EGFR and PD-1 expression and mutations in tumor tissue (Phase I and II)

Response assessed using irRECIST, immune-related Response Criteria (irRC), and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase I and II)

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

Pembrolizumab

2017

Completed Phase 2

~2070

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The CIMAvax vaccine targets the epidermal growth factor (EGF), which is crucial for tumor growth and proliferation. By inducing an immune response against EGF, CIMAvax aims to slow down or stop tumor growth. Nivolumab and Pembrolizumab are PD-1 inhibitors that work by blocking the programmed cell death protein 1 (PD-1) pathway, which tumors exploit to evade the immune system. By inhibiting this pathway, these drugs enhance the body's immune response against cancer cells. These mechanisms are significant for NSCLC patients as they offer targeted approaches to hinder tumor growth and improve immune system efficacy, potentially leading to better treatment outcomes.

Emerging therapeutic agents for lung cancer.CIMAvax-EGF, a therapeutic non-small cell lung cancer vaccine.