Personalized Vaccine with Pembrolizumab for Advanced Solid Tumors
This study is testing a personalized neoantigen peptide vaccine along with pembrolizumab (an immunotherapy drug) to see if this combination is safe and effective for people with advanced solid tumors, including certain stages of breast cancer. The vaccine is designed to target specific proteins (neoantigens) on your tumor cells. Researchers will be looking at how well the treatment works and if there are any side effects. To join, you would need to be willing to provide tissue samples for genetic testing. The study is no longer enrolling for Cohorts 1 and 2, but other parts of the study may still be open.
- Study design
- This is an interventional study with a planned enrollment of 132 participants. It is testing the safety and effectiveness of a personalized vaccine in combination with pembrolizumab.
- What's involved
- You would receive Cyclophosphamide, the personalized neoantigen vaccine, Pembrolizumab, and Sargramostim. You would also undergo blood sample collection and provide tissue specimens.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your adverse events will be measured for up to 2 years from the first vaccine administration.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05269381
Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors
Recruiting
PHASE1Ages 16+InterventionalTreatmentMayo ClinicInvestigator-initiated
~138 participants
Updated 2026-08-20 on ClinicalTrials.gov
What's tested:CyclophosphamideNeoantigen Peptide VaccinePembrolizumabSargramostimBiospecimen CollectionBiopsy
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximally tolerated dose (MTD) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)
Measured over Up to 2 years
+4 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesFlorida1
Study leadership
- Yanyan Lou, MD, PhD · PRINCIPAL_INVESTIGATOR · Mayo Clinic
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
Provide written informed consent. For pediatric patients (age 16-17 years):
Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
Willing to return to enrolling institution for follow-up
Willing to provide blood specimens for research
Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
Anticipated life expectancy \> 6 months
The following lab values obtained ≤ 28 days prior to pre-registration:
Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
Successful sequencing and production of REAL-Neo vaccine
Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
ECOG PS 0 or 1
Anticipated life expectancy \> 6 months
The following lab values obtained ≤ 14 days prior to registration:
Hemoglobin ≥ 9.0 g/dl
ANC ≥ 1500/mm\^3
Platelet count ≥ 100,000/mm\^3
Total bilirubin ≤ 1.5 x ULN
ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
Provide written informed consent
Willing to provide blood and tissue specimens for research
Willing to return to enrolling institution for follow-up
Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy
Negative pregnancy test ≤ 14 days prior to registration for persons of childbearing potential only
NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required
Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
Recovered from all toxicities associated with prior treatment to acceptable baseline status or NCI CTCAE v5 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)
ECOG PS 0 or 1
Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \< 10%, progesterone receptor (PR) \< 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline
Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)
Evidence of residual disease ≥ 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery
Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery, willing to provide clinically collected FFPE tissue blocks, or willing to provide available sequencing data available from commercial or research test
Provide written informed consent
Willing to return to enrolling institution for follow-up
ECOG PS 0 or 1
Histological confirmation of lung NSCLC
No actionable EGFR mutations and ALK fusions
Stage II or stage III based on AJCC 8th
Tumor ≥ 2 cm on pre-surgery evaluation imaging (residual disease ≥ 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed
Provide written informed consent
Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery
Willing to return to enrolling institution for follow-up
Histologically confirmed residual cancer burden 2 and 3 in surgical specimens
Tumor without complete pathologic response is confirmed in pathology
Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
ECOG PS of 0 or 1
Anticipated life expectancy \> 6 months
Provide written informed consent. For pediatric patients (age 16-17 years):
Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations
Willing to proceed with surgery and provide mandatory tissue specimens or previously collected FFPE tissues for complete exome and transcriptome sequencing or available sequencing data available from commercial or research test
NOTE: Patients who had sequencing under Mayo IRB protocol #13-000942, #14-004094, or #21-007742 and neoantigens have been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration
Negative pregnancy test done ≤ 7 days prior to pre-registration for persons of childbearing potential only
NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Willing to employ a highly effective method of contraception from the time of preregistration through 6 months after the final vaccine cycle
ECOG performance status of 0 or 1
Anticipated life expectancy of \> 6 months
Willing to return to enrolling institution for follow-up
Histologically confirmed invasive lobular carcinoma or other histology with lobular features
Histological confirmation of adenocarcinoma of the breast with invasive lobular histology or other histology with lobular features with any estrogen receptor (ER), progesterone receptor (PR), and HER2 status
Stage II-IV based on the 7th edition of TNM staging system from AJCC
Tumor mutational burden ≥ 10 muts/Mb either in tissue or blood
Successful sequencing and production of REAL-Neo vaccine
Patients will receive ≥ 2 additional cycles of maintenance pembrolizumab
ECOG PS 0 or 1
Anticipated life expectancy \> 6 months
Lab values as per Phase I registration criteria obtained ≤ 14 days prior to registration:
Provide written informed consent
Willing to provide blood specimens for research
Willing to return to enrolling institution for follow-up
Negative pregnancy test ≤ 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.
Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior registration
Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE v5 grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)
Exclusion
Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:
Pregnant person
Nursing person unwilling to stop breast feeding
Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle
Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens
History of myocardial infarction ≤ 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment
Uncontrolled illness including, but not limited to:
Ongoing or active infection
Psychiatric illness/social situations
Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease
Stroke ≤ 3 months prior to pre-registration
Significant cardiac arrhythmia or unstable angina
Any other conditions that would limit compliance with study requirements
Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab
Any prior hypersensitivity or adverse reaction to GM-CSF
Other active malignancy ≤ 3 years prior to pre-registration
EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer
History of active autoimmune disease (AD) that required systemic treatment in ≤ 30 days (i.e., use of disease modifying agents, corticosteroids \> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration
NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION
Any of the following prior therapies:
Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) ≤ 3 weeks prior to cycle 1 day 1 (C1D1) neoantigen vaccinations
Radiation ≤ 2 weeks prior to C1D1 neoantigen vaccinations
Major Surgery ≤ 4 weeks prior to C1D1 neoantigen vaccinations
Received live vaccine ≤ 30 days prior to C1D1 neoantigen vaccinations
NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \> 14 days from first dose of vaccination on study
CTCAE ≥ Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity
Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis
Active ADs that require chronic systemic steroids (\> 10 mg daily prednisone equivalent) or immunosuppressive agents
Systemic corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications ≤ 14 days prior to registration
NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent permitted in absence of active AD
Patients will also be excluded based on tissue/RNA/DNA quality and quantity. If any of the following quality and quantity thresholds are not met, the patient will be excluded:
Tumor tissue cellularity ≥ 30%
Sufficient tissue (fresh frozen or FFPE) for both DNA and RNA sequencing with passing cellularity.
≥ 30% of tumor RNA with fragment sizes are ≥ 200 base pairs (DV200 ≥ 30)
\< 10% of DNA fragments are smaller than 1 kb
Sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and RNAseq according to the Mayo sequencing core (note: kits and technologies change over time, so these are not fixed numbers)
Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \>10 mg daily prednisone equivalent
NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)
Uncontrolled illness including, but not limited to:
Ongoing or active infection
CHF with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease
Significant cardiac arrhythmia or unstable angina
Any other conditions that would limit compliance with study requirements
Any prior hypersensitivity or adverse reaction to GM-CSF
Other active malignancy ≤ 3 years prior to pre-screening
EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer
Known history of active AD that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening
NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.
Uncontrolled illness including, but not limited to:
Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease
Significant cardiac arrhythmia or unstable angina
Any other conditions that would limit compliance with study requirements
Any prior hypersensitivity or adverse reaction to GM-CSF
Other active malignancy ≤ 3 years prior to pre-registration
EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer
Known history of active AD that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids \> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration
NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.
Patients will also be excluded based on tissue/RNA/DNA quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are ≥ 2 cores with passing cellularity; (3) ≥ 30% of tumor RNA with fragment sizes are ≥ 200 base pairs (DV200 ≥ 30); (4) \< 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)
Evidence of metastatic disease or recurrence
Any of the following prior therapies:
Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) ≤ 3 weeks prior to study treatment
Radiation ≤ 2 weeks prior to study treatment
Major surgery ≤ 4 weeks prior to study treatment
Received live vaccine ≤ 30 days prior to study treatment
NOTE: Continuation of pembrolizumab per standard of care is allowed
NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \> 14 days from first dose of vaccination on study
CTCAE ≥ grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity
Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis
Active ADs that require chronic systemic steroids (\> 10 mg daily prednisone equivalent) or immunosuppressive agents
What this trial measures
- Maximally tolerated dose (MTD) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)Up to 2 years
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. For instance, those toxicities with an incidence of at least 25% will be observed with a probability of at least 82% (1-(1-0.25).
- Dose Limiting Toxicity (DLT) (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)Up to 2 years
DLT are defined to be adverse event (AE) occurring from day -3 through day 35 that is possibly, probably, or definitely related to neoantigen peptide vaccine with/without pembrolizumab and fulfills any of the following criteria using the National Cancer Institute's Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0
- Incidence of adverse events (Phase I, Cohort 1, Cohort 2, and Pilot Cohort 5)Up to 2 years from first vaccine administration
The number and severity (grade) of all treatment related adverse events (AEs) will be tabulated and summarized. Non-hematologic AEs will be evaluated via the ordinal CTCAE v5.0 standard AE grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTCAE v5.0 standard AE grading. Both all grade and grade 3 and above AEs will be described and summarized in a similar fashion. Overall AE incidences as well as AE profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Event free survival (EFS) (Phase II Cohort 3)Up to 2 years
EFS is defined as the length of time after primary treatment for a cancer ends until occurrence of complications or events that the treatment was intended to prevent or delay.
- Disease-free survival (DFS) (Phase II Cohort 4)Up to 2 years
DFS is defined as the length of time after primary treatment for a cancer ends until any signs or symptoms of that cancer recur.