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Universal Immunization to Fortify Immunotherapy Efficacy and Response

ConditionStage 4 NSCLC
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Florida

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Pfizer-BioNTech mRNA COVID-19 vaccine

    Biological/Vaccine

    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.

Treatment groups

500 Participants
are divided into 3 treatment groups
Group A: Arm 1 : InterventionActive comparator 1 intervention
Group B: Arm 2: No Intervention (Control Arm)No intervention 0 interventions
Group C: Patient-Preference CohortNo intervention 0 interventions

Trial outcomes

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.

Time frame
60 days after the start of treatment with pembrolizumab and chemotherapy

Secondary outcomes

1

Progression-free survival

Determine the progression-free survival among all randomized subjects. Progression-free survival is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first.

Time frame
5 years
2

Progression-free survival

Determine the progression-free survival among randomized subjects receiving first line of immune checkpoint inhibitor therapy without brain metastases. Progression-free survival is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first.

Time frame
5 years
3

Progression-free survival

Determine the progression-free survival among randomized subjects receiving combination PD-1 and CTLA-4 directed immune checkpoint inhibitor therapy. Progression-free survival is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first.

Time frame
5 years
4

Change in tumor proportion score

Determine the change in tumor proportion score within 100 days of receiving Pfizer-BioNTech COVID mRNA vaccine among randomized patients with biopsy obtained as standard of care.

Time frame
100 days after receipt of Pfizer-BioNTech COVID mRNA vaccine

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Florida

Lead sponsor

M.D. Anderson Cancer Center

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: