What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC), particularly those involving immunotherapy and chemotherapy combinations like the Pooled Mutant-KRAS Peptide Vaccine with Poly-ICLC Adjuvant, often result in a range of side effects. Immune checkpoint inhibitors such as nivolumab and ipilimumab can lead to immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Chemotherapy agents like docetaxel are associated with myelosuppression, neuropathy, fatigue, and gastrointestinal symptoms. The combination of these therapies can increase both the incidence and severity of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Small Cell Lung Cancer (NSCLC) that are similar to the Pooled Mutant-KRAS Peptide Vaccine with Poly-ICLC Adjuvant. These include immune checkpoint inhibitors like nivolumab and ipilimumab, which target PD-1 and CTLA-4 pathways to enhance immune response against cancer cells. Additionally, targeted therapies for specific mutations, such as EGFR inhibitors (e.g., gefitinib) and HER2-targeted treatments (e.g., fam-trastuzumab deruxtecan), have also been approved. These therapies aim to improve progression-free survival and overall survival in patients with advanced NSCLC.

What other types of research exist?

Promising novel alternatives for NSCLC patients include: 1) Combination therapies involving immune checkpoint inhibitors such as nivolumab and ipilimumab, which have shown efficacy in various studies. 2) Personalized neoantigen vaccines targeting specific tumor mutations, which are being explored for their potential to elicit strong immune responses. 3) NK cell-based immunotherapies combined with anti-EGFR antibodies, which have shown potential in preclinical studies. These alternatives offer different mechanisms of action and may provide additional options for patients in 2024.

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Checkpoint Inhibitor

KRAS Vaccine + Immunotherapy for Lung Cancer

Phase 1

Recruiting

Led By Kristen Marrone, MD

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

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

Must have

Histologically- or cytologically-proven adenocarcinoma of the lung deemed to be locally advanced/unresectable or metastatic as per American Joint Committee on Cancer (AJCC) version 8, who has not received prior therapy for this stage of disease.

Have one of the six KRAS mutations (KRAS G12C, KRAS G12V, KRAS G12D, KRAS G12A, KRAS G13D or KRAS G12R) in vaccine expressed in tumor as defined by a Clinical Laboratory Improvement Amendments (CLIA) certified tumor or plasma based genomic testing platform performed either through a local laboratory or through the investigators' central laboratory.

Must not have

Has a diagnosis of immunodeficiency.

Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to progression, up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a special vaccine combined with immune-boosting substances and two drugs in advanced lung cancer patients with specific genetic mutations. The goal is to teach the immune system to attack the cancer cells more effectively.

Who is the study for?

Adults with advanced, inoperable KRAS-mutated non-small cell lung cancer (NSCLC) who haven't had prior treatment for this stage. Participants must have tumors that can be biopsied, good physical health (ECOG 0 or 1), and proper organ function. Women of childbearing age and sexually active men must agree to contraception use.

What is being tested?

The trial is testing a new vaccine targeting specific KRAS mutations in NSCLC combined with the immune checkpoint inhibitors nivolumab and ipilimumab. It aims to assess safety, feasibility, and how well it prevents disease progression.

What are the potential side effects?

Potential side effects include typical reactions from vaccines such as soreness at injection site, fatigue, flu-like symptoms; plus risks from immunotherapy like inflammation in organs, skin issues, hormonal changes or autoimmune responses.

Eligibility Criteria

Inclusion Criteria

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

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My lung cancer is advanced and has not been treated yet.

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My tumor has one of the six specific KRAS mutations.

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I am using at least one barrier method of contraception.

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I received my last chemotherapy or radiation therapy less than 6 months ago.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

Exclusion Criteria

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

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I have been diagnosed with an immune system disorder.

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I have not had any organ or tissue transplants, including bone marrow.

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I have a history of HIV, hepatitis B, or hepatitis C.

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I have brain metastases that haven't been treated or are causing symptoms.

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I do not have any serious illnesses that could interfere with the study.

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I have had lung inflammation that needed steroids or have it now.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to progression, up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to progression, up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to progression, up to 4 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Feasibility of administering a KRAS peptide vaccine in combination with nivolumab and ipilimumab as assessed by adverse events

Safety of administering a KRAS peptide vaccine in combination with nivolumab and ipilimumab as assessed by adverse events

Secondary study objectives

Change in interferon-producing mutant-KRAS-specific CD 4 T cells in the peripheral blood

Change in interferon-producing mutant-KRAS-specific cluster of differentiation (CD) 8 T cells in the peripheral blood

Progression Free Survival (PFS) as assessed by imaging

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Patients With NSCLCExperimental Treatment1 Intervention

All participants will receive the intervention.

0 / 12Eligibility 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 most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors and ALK inhibitors, block specific molecular pathways essential for cancer cell growth. Immunotherapies, like immune checkpoint inhibitors (e.g., nivolumab and ipilimumab), enhance the immune system's ability to attack cancer cells. The Pooled Mutant-KRAS Peptide Vaccine with Poly-ICLC Adjuvant aims to activate the immune system specifically against KRAS-mutated cancer cells, potentially improving treatment outcomes. These approaches are crucial for NSCLC patients as they provide more personalized and effective treatment options based on individual genetic and immune profiles.

Radiation-induced bystander and abscopal effects: important lessons from preclinical models.Mechanisms of tumor immunotherapy, with a focus on thoracic cancers.