A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma

Inclusion Criteria:

1. Ability to understand and willingness to sign an informed consent form.

2. Subjects of at least 18 years of age with histologically confirmed diagnosis ofadenocarcinoma.

3. Subjects with advanced/metastatic or recurrent solid tumors, with measurable ornon-measurable disease as determined by RECIST version 1.1 are eligible forparticipation.

4. For Phase 2, Cohort A, participants must have:

5. Histologically confirmed diagnosis of labyrinthin-positive lung adenocarcinoma.

6. Received at least one line of anti-PD-1 or anti-PD-L1 therapy for any stage ofNSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in combination withother therapy.

7. Progressed on at least one line of therapy if participant has a knownsensitizing mutation for which an FDA-approved targeted therapy for NSCLCexists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, and MET sensitizing mutations).

8. For Phase 2, all subjects must be candidates for pembrolizumab therapy.

9. Subjects can either have progressed, had no response, or intolerance to prior cancertherapy. Patients must have recovered from all clinically significanttreatment-related toxicities to grade 1 or less, except chemotherapy-associatedperipheral neuropathy (motor or sensory), or endocrine-related AE, in which recoveryto ≤ Grade 2 is allowed. For endocrine-related AEs, physiological doses ofreplacement therapy (e.g., levothyroxine, insulin, hydrocortisone, or otherreplacement therapy for adrenal or pituitary insufficiency, etc.) are allowed.

10. No limit on prior lines of therapy for metastatic disease. Prior chemotherapy,immunotherapy (including pembrolizumab) or molecularly targeted therapy must havebeen completed at least 3 weeks prior to initiating study treatment. Priorpalliative radiation must have been completed at least 2 weeks prior to initiatingstudy treatment.

11. Subjects with known untreated, active brain and/or leptomeningeal metastases areexcluded. Subjects with treated brain metastasis who are neurologically stable andoff steroids for at least one week are eligible.

12. All subjects must have an ECOG performance status of 0-1. 10 All subjects must havea life expectancy of ≥ 6 months at the time of initiating study treatment.

13. Subjects must demonstrate adequate organ function as defined below:

• Absolute neutrophil count (ANC) ≥1,000 cells / μL

• Absolute lym75,000 cells/μL

• Creatinine clearance as calculated per Cockcroft-Gault or MDRD formula ≥30 mL/min

• Total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for participants with totalbilirubin levels > 1.5 ULN

• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN or ≤ 5 X ULN for subjects with liver 12.Because the effects of the study treatment on the unborn fetus or nursing infant areunknown, pregnant and nursing women are ineligible. Women of childbearing age musthave a negative urine or serum pregnancy test (HCG) within 72 hours prior toreceiving the first dose of study medication. If the urine test is positive orcannot be confirmed as negative, a serum pregnancy test will be required.

13. Confirmation of adequate archival tumor specimens (i.e., sufficient specimensfor ten, 5-7 µm thick, unstained sections).

Exclusion Criteria:

1. Subjects who have autoimmune diseases that require immunosuppressive medicationsother than prednisone ≤ 10 mg daily or equivalent. Physiological doses ofreplacement therapy (e.g., levothyroxine, insulin, hydrocortisone, or otherreplacement therapy for adrenal or pituitary insufficiency, etc.) are not considereda form of immunosuppressant and are allowed.

2. Subjects who have had a prior splenectomy are ineligible.

3. Pregnant or nursing women.

4. Any medical condition including additional malignancies, laboratory abnormalities,or psychiatric illness that in the opinion of the investigator would prevent thesubject from participating and adhering to study related procedures.

5. Uncontrolled concomitant disease that in the opinion of the investigator wouldinterfere with the subject's safety or compliance on trial.

6. Severe infection that in the opinion of the investigator would interfere withsubject safety or compliance on trial within 4 weeks prior to enrollment.

7. Subjects who have contraindications to GM-CSF injections according to the packageinsert (e.g., subjects with excessive leukemic myeloid blasts in the bone marrow orperipheral blood (≥ 10%); known hypersensitivity to GM-CSF, yeast-derived productsor any component of the product). Additional exclusion criteria for participants entering Phase 2:

8. Is receiving systemic steroid therapy (> 10 mg prednisone oral daily or equivalent)or any other form of immunosuppressive therapy within 7 days prior to the first doseof trial treatment.

9. Has a known history of active TB (Bacillus Tuberculosis)

10. Hypersensitivity to pembrolizumab or any of its excipients.

11. Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to studyDay 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse eventsdue to agents administered more than 3 weeks earlier.

12. Has had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeksprior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) fromadverse events due to a previously administered agent.

• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion andmay qualify for the study.

• Note: If subjects received major surgery, they must have recovered adequatelyfrom the toxicity and/or complications from the intervention prior to startingtherapy.

13. Has known untreated, symptomatic central nervous system (CNS) metastases and/orcarcinomatous meningitis. Subjects with previously treated brain metastases mayparticipate provided they are stable (without evidence of progression by imaging forat least four weeks prior to the first dose of trial treatment and any neurologicsymptoms have returned to baseline), have no evidence of new or enlarging brainmetastases requiring treatment, and are not using steroids (> 10 mg prednisone oraldaily or equivalent) for at least 7 days prior to trial treatment. This exceptiondoes not include carcinomatous meningitis which is excluded regardless of clinicalstability.

14. Has known history of ≥ grade 3 pneumonitis or interstitial lung disease related toradiation, immunotherapy, chemotherapy, or targeted therapy.

15. Has an active infection requiring systemic therapy.

16. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thesubject's participation for the full duration of the trial, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

18. Has received a live vaccine within 30 days of planned start of study therapy.

• Note: Seasonal influenza vaccines for injection are generally inactivated fluvaccines and are allowed; however intranasal influenza vaccines (e.g.,Flu-Mist®) are live attenuated vaccines, and are not allowed. COVID vaccinesare allowed.