This is a phase 1 study to evaluate the safety, the Recommended Phase 2 Dose (RP2D), and
preliminary efficacy of a personalized neoepitope yeast-based vaccine, YE-NEO-001, in
subjects who have completed potentially curative therapy for their solid cancer and who would
otherwise be entering a period of surveillance for recurrent disease.
This is a phase 1 trial to evaluate the safety, the RP2D, and preliminary efficacy of a
personalized neoepitope yeast-based vaccine, YE-NEO-001, in subjects who have completed
potentially curative therapy for their type of solid cancer (eg, colorectal cancer, breast
cancer, head and neck squamous cell carcinoma, melanoma) and would otherwise be entering a
period of surveillance for recurrent disease.
The study will be conducted in two parts: part 1 will involve dose escalation, and part 2
will involve the expansion of the RP2D to further evaluate the safety of YE-NEO-001. In part
2 of the study, dose expansion will occur when the RP2D has been determined. An additional 4
subjects may be enrolled in part 2, for a total of up to 10 subjects at the RP2D.
Inclusion Criteria:
Pre-treatment Phase: Tissue Procurement and Development of Vaccine
1. Age ≥ 18 years old.
2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or IEC guidelines.
3. Histologically-confirmed cancer amenable to treatment with curative intent as part of
SoC. Must be willing to provide a tumor tissue sample (either a tumor biopsy specimen
or tissue from resected tumor not used for diagnostic purposes) and a blood sample for
tumor molecular profiling.
- Solid cancers include any of the following surgically resectable cancers:
colorectal cancer, head and neck squamous cell carcinoma, non-small cell lung
cancer, breast cancer (either hormone receptor positive, HER2-positive or
negative, or triple-negative breast cancer), pancreatic cancer, liver cancer, and
melanoma. Curative therapy, whether surgery, radiation therapy, or adjuvant
chemotherapy, must be completed per National Comprehensive Cancer Network (NCCN)
guidelines.
4. Must be willing to agree to initiation of development of personalized YE-NEO-001
vaccine.
Treatment Phase:
1. No evidence of disease (NED) at first assessment post multi-modality therapy (ie,
surgery and/or radiation therapy and/or chemotherapy). Subjects treated with
definitive radiation therapy are considered NED if they have no evidence of cancer
growth on the first and second surveillance CT scans. Subjects who have disease
recurrence prior to the start of the vaccination process are also eligible if no
satisfactory alternative treatment options are available or if subject has refused all
other available therapies.
2. Must have received < 6 months of SoC therapy.
3. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or IEC guidelines.
4. ECOG performance status of 0 to 2.
5. Must be willing to provide blood samples prior to the start of treatment on this study
for exploratory analyses.
6. If cancer recurs while on treatment on this study, must be willing to provide a tumor
biopsy specimen for exploratory analyses, if considered safe by the Investigator.
7. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.
8. Agreement to practice effective contraception for female subjects with child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception for up to 1 year after completion of therapy, and
non-sterile male subjects must agree to use a condom for up to 4 months after
treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
spermicide, IUDs, and abstinence.
Exclusion Criteria:
Pre-treatment Phase: Tissue Procurement and Development of Vaccine
1. Unable or unwilling to attend required study visits and return for adequate follow-up,
as required by this protocol.
Treatment Phase:
1. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
treatment-related complications.
2. Active autoimmune disease requiring systemic immunosuppressive treatment within 4
weeks prior to enrollment on this study (eg, lupus erythematosus, rheumatoid
arthritis, Addison's disease, autoimmune disease associated with lymphoma, ankylosing
spondylitis, scleroderma, multiple sclerosis). A history of inactive autoimmune
disease or autoimmune disease not requiring systemic immunosuppressive therapy within
4 weeks prior to study enrollment is allowed.
3. History of organ transplant requiring immunosuppression.
4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).
5. Inadequate organ function, evidenced by the following laboratory results:
1. ANC < 1,000 cells/mm^3.
2. Platelet count < 75,000 cells/mm^3.
3. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
4. Total bilirubin > ULN (unless the subject has documented Gilbert's syndrome).
5. AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases).
6. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases, or > 10 × ULN in subjects with bone metastases).
7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with
uncontrolled hypertension should be medically managed on a stable regimen to control
hypertension prior to study entry.
7. Positive results of screening test for HIV.
8. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
9. Known hypersensitivity to any component of the study medication(s).
10. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
reaction with the study treatment. Anti-androgen and anti-estrogen medications are
allowed.
11. Participation in an investigational drug study or history of receiving any
investigational treatment within 30 days prior to initiation of treatment on this
study, except for testosterone-lowering therapy in men with prostate cancer.
12. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
13. Concurrent participation in any interventional clinical trial.
14. Pregnant and nursing women.
