Although immune checkpoint inhibitors (ICIs) have substantially extended survival in manypatients, most patients do not achieve durable responses on these treatments. There is asubstantial unmet need for methods to sensitize more patients to ICIs. Studies have shownthat personalized mRNA lipid nanoparticle vaccines enhance antitumor immunity incombination with PD1 inhibition, under the assumption that these vaccines generate Tcells reactive against the targets encoded by the mRNA in the vaccines. However, it wasrecently found that mRNA vaccines targeting non-tumor antigens are also powerfuladjuvants to immune checkpoint blockade.Retrospective clinical data strongly suggests that receipt of COVID mRNA vaccines withICIs is responsible for significant improvements in three-year overall survival inmultiple large cohorts of patients with non-small cell lung cancer (NSCLC). Patientstreated 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 vaccineimproves responses to ICIs in patients with stage IV non-small cell lung cancer.
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Biological: Pfizer-BioNTech mRNA COVID-19 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.
Inclusion Criteria:
- 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)
- 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.
Exclusion Criteria:
- 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.
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