Stage 4 NSCLCPhase 2UNIFIERNCT07597070
Universal Immunization to Fortify Immunotherapy Efficacy and Response
A Phase 2 study testing Pfizer-BioNTech mRNA COVID-19 vaccine in people with Stage 4 NSCLC, run by University of Florida.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage 4 NSCLC
- What is being tested?
- Pfizer-BioNTech mRNA COVID-19 vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Mar 2035
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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)
- Intrauterine device (IUD, made of copper or progestin)
- Hormonal contraception
- Birth control pills (combined (estrogen and progestogen containing))
- Contraceptive vaginal ring (i.e. NuvaRing)
- Patch (i.e. Xulane)
- Progestin only pill (mini pill)
- Depo-Provera (birth control shot or Depo)
- Abstinence
- Vasectomized male partner
- WOCBP includes any subject who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
- For subjects with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
- Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 5 months following the last dose of study treatment.
Who cannot join
- 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.
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- 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.
About this study
Official title: Universal Immunization to Fortify Immunotherapy Efficacy and Response (UNIFIER)
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
- Being tested
- Pfizer-BioNTech mRNA COVID-19 vaccine
- Keywords
- COVID, immune checkpoint inhibitor, non-small cell lung cancer, mRNA vaccine, stage 4
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pfizer-BioNTech mRNA COVID-19 vaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 : Intervention | Active comparator | Not described Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 days after the start of treatment with pembrolizumab and chemotherapy
Secondary outcomes (5)
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.
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 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
Determine the percentage of randomized subjects who experience a delay related to vaccine in starting immune checkpoint inhibitor therapy after receiving COVID-19 mRNA vaccine. A subject is considered to experienced a delay if immune checkpoint inhibitor therapy is started 14 days or more after randomization.
Measured: 14 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2026
- Study startNov 2026 (estimated)
- Primary completionMar 2035 (estimated)
- Study completionMar 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage 4 NSCLCStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
- Investigators
- Elias Sayour, MD, PhD, Principal investigator, University of FloridaSteven Lin, MD, PhD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07597070
- Sponsor's protocol ID
- UF-THO-008
- Acronym
- UNIFIER
- Status last verified
- Sep 2026
- First submitted
- 12 May 2026
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No