Universal Immunization to Fortify Immunotherapy Efficacy and Response

NCT07597070 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UF-THO-008
• Study Type: interventional
• Target: 500
• Locations: 0 countries
• Sites: N/A

Brief Summary

Although immune checkpoint inhibitors (ICIs) have substantially extended survival in many patients, most patients do not achieve durable responses on these treatments. There is a substantial unmet need for methods to sensitize more patients to ICIs. Studies have shown that personalized mRNA lipid nanoparticle vaccines enhance antitumor immunity in combination with PD1 inhibition, under the assumption that these vaccines generate T cells reactive against the targets encoded by the mRNA in the vaccines. However, it was recently found that mRNA vaccines targeting non-tumor antigens are also powerful adjuvants to immune checkpoint blockade. Retrospective clinical data strongly suggests that receipt of COVID mRNA vaccines with ICIs is responsible for significant improvements in three-year overall survival in multiple large cohorts of patients with non-small cell lung cancer (NSCLC). Patients treated with these vaccines also have increased expression of programmed death ligand 1 (PD-L1) on their tumors. This trial is designed to evaluate whether the Pfizer-BioNTech COVID mRNA vaccine improves responses to ICIs in patients with stage IV non-small cell lung cancer.

Conditions

Stage 4 NSCLC

Keywords

COVID; immune checkpoint inhibitor; non-small cell lung cancer; mRNA vaccine; stage 4

Outcome Measures

Primary Outcomes (1)

• Incidence of immune-related adverse events requiring hospitalization

  Determine the incidence for randomized subjects of immune response adverse events requiring hospitalization within 60 days of starting planned treatment with pembrolizumab and chemotherapy.

  60 days after the start of treatment with pembrolizumab and chemotherapy

Secondary Outcomes (5)

• Progression-free survival

  5 years

• Progression-free survival

  5 years

• Progression-free survival

  5 years

• Change in tumor proportion score

  100 days after receipt of Pfizer-BioNTech COVID mRNA vaccine

• Feasibility of administering COVID-19 mRNA vaccine within 7 days prior to initiating immune checkpoint inhibitor therapy

  14 days after randomization

Study Arms (3)

Arm 1 : Intervention

ACTIVE COMPARATOR

Biological: Pfizer-BioNTech mRNA COVID-19 vaccine

Arm 2: No Intervention (Control Arm)

NO INTERVENTION

Participants on this arm will not receive the Pfizer COVID-19 mRNA vaccine before beginning their planned treatment with pembrolizumab and chemotherapy. They will begin their planned therapy within a week of randomization.

Patient-Preference Cohort

NO INTERVENTION

Eligible participants who provide consent but decline randomization will be enrolled in this patient-preference cohort and the reasons for declining randomization will be documented. Participants in this cohort may choose whether to receive a COVID-19 mRNA vaccine before or after beginning their planned therapy with pembrolizumab and chemotherapy.

Interventions

Pfizer-BioNTech mRNA COVID-19 vaccine BIOLOGICAL

Participants will receive a Pfizer-BioNTech COVID-19 mRNA vaccine within 7 days before initiating their immune checkpoint inhibitor therapy. Participants will receive the mRNA COVID-19 vaccine at their local pharmacy and this vaccine will not be provided by the study site. The vaccine is expected to change during the study. Participants will obtain the most up-to-date Pfizer COVID-19 mRNA vaccine available for which they qualify under standard of care.

Arm 1 : Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age.
• Histologically or cytologically confirmed stage IV non-small cell lung cancer (NSCLC), defined as: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and NSCLC not otherwise specified; with clinical disposition to front-line therapy, with pembrolizumab and chemotherapy
• ECOG Performance Status of 0 to 2.
• Willing to receive Pfizer-BioNTech mRNA COVID-19 vaccine (for vaccine arms).
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.
• Subjects must not have more than one active malignancy at the time of enrollment (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen or primary endpoint \[as determined by the treating physician or approved by the PI\] are eligible for this trial).
• Women of childbearing potential (WOCBP) will be given a pregnancy test (blood or urine) prior to the start of treatment and must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 5 months after the last dose of study treatment to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• Adequate contraception methods for WOCBP include:
• Barrier methods
• Male and female condoms
• Vaginal diaphragm
• Cervical cap
• Vaginal sponge
• Hormonal medication and devices
• Birth control implant (i.e. Nexplanon)

You may not qualify if:

• Dispositioned to targeted therapy (e.g., EGFR, ALK, ROS1).
• Determination by the treating physician that treatment with pembrolizumab with chemotherapy is not an appropriate intervention for the participant.
• Known hypersensitivity or allergy to any component of the mRNA COVID-19 vaccines (Pfizer-BioNTech or Moderna), including polyethylene glycol (PEG) or polysorbate
• Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose.
• Receipt of any other COVID-19 vaccine or investigational vaccine within 60 days prior to enrollment.
• Uncontrolled or unstable comorbid conditions (e.g., active infection, unstable cardiovascular disease, history of vaccine-related myocarditis, or uncontrolled autoimmune disease) that, in the opinion of the investigator, could interfere with study participation or pose additional risk.
• History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
• Subjects who are confirmed to be pregnant or breastfeeding.
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Sponsors & Collaborators

• University of Florida: lead
• M.D. Anderson Cancer Center: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Elias Sayour, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Steven Lin, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1 ratio to either Arm 1 (Vaccine arm) or Arm 2 (Control arm). Eligible patients who would prefer not to be randomized will be enrolled on the patient preference cohort.

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2035
• Study Completion (Estimated): March 1, 2035
• Last Updated: June 8, 2026

Record last verified: 2026-06