A First-in-human (FIH) Combination Treatment Study With a Single Dose Level of BMC128

Inclusion Criteria:

1. Capable of providing signed informed consent to participate in the study, and tocomply with the requirements and restrictions listed in the protocol.
2. ≥18 years of age at time of informed consent
3. Histologically or cytologically confirmed metastatic or locally advanced unresectableclear cell renal cell carcinoma (ccRCC), cutaneous melanoma, or EGFR/ ALK wildtypeadenocarcinoma-type non-small cell lung carcinoma (NSCLC).
4. At least one measurable lesion per RECIST v 1.1 criteria
5. Subjects must have progressed on treatment with a PD-1/PD-L1 inhibitor administeredeither as monotherapy, or in combination with other checkpoint inhibitors or othertherapies. PD-1/PDL-1 inhibitor treatment progression is defined by meeting all of thefollowing criteria:
6. Has received at least 2 doses of a PD-1/PD-L1 inhibitor.
7. Has demonstrated disease progression after PD-1/PD-L1 therapy as defined byRECIST v1.1, iRECIST or irRECIST. The initial evidence of disease progression (PD) is to be confirmed by a second assessment no less than four weeks from thedate of the first documented PD, in the absence of rapid clinical progression.
8. Progressive disease has been documented within 12 weeks from the last dose of aPD-1/PD-L1 inhibitor.
9. Subjects must have had prior response to anti-PD1/PDL-1 as single agent or incombination with other cancer therapies, defined as at least stable disease periRECIST, as assessed by 2 consecutive imaging ≥ 4 weeks apart, with the first oneperformed no earlier than 9 weeks from initiation of anti PD1/PDL-1 treatment.
10. Subjects must demonstrate adequate organ functions at Screening:
11. Absolute neutrophil count ≥1500/μL, platelet count ≥100,000/μL; hemoglobin ≥9.0g/dL Note: Patients must not have received any growth factors or bloodtransfusions within 28 days prior to the Screening hematologic laboratory tests
12. Total bilirubin <1.5 × the upper limit of normal (ULN) (with the exception ofpatients diagnosed with Gilbert syndrome), Alanine aminotransferase or aspartateaminotransferase <1.5 × ULN
13. Creatinine ≤ 1.5 ULN and/or estimated glomerular filtration rate ≥ 60
14. Albumin >30 g/L (3.0 g/dL)
15. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
16. Female subjects of childbearing potential should have a negative urine pregnancy testwithin 72 hours prior to enrolment (enrolment = start of depletion phase). If urinepregnancy results cannot be confirmed as negative, a SERUM β-HCG pregnancy test isrequired. Subjects of childbearing potential are those who have not been surgicallysterilized or those age < 60 y who have not been free from menses for ≥2 years.
17. Female subjects of childbearing potential must be willing to use 2 methods of birthcontrol starting from the start of the induction phase or be surgically sterile, orabstain from heterosexual activity throughout the course of the study and 120 daysafter the last dose of study medication
18. Male subjects with female partners of childbearing potential should agree to use anadequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

1. History of partial or complete colon resection or colonic dissemination of tumor.
2. Active brain metastases or leptomeningeal disease. Subjects with asymptomatic centralnervous system (CNS) metastases which have been stable (defined as without evidence ofprogression by magnetic resonance imaging (MRI) for at least 42 days prior toenrolment (initiation of depletion phase) and any neurologic symptoms have returned tobaseline) following treatment with surgery or radiation therapy are allowed.
3. Prior solid organ or hematologic transplant.
4. Prior treatment with PD1/ PDL-1 inhibitor in combination with an immune-modifyingmicrobiome agent.
5. History of treatment-related immune-mediated (or immune-related) adverse reactions toimmune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents,anti-CTLA4 monoclonal antibodies) that caused permanent discontinuation of the agent,or that were grade 3 or 4 in severity. Subjects with grade 3-4 hypothyroidism, primaryadrenal insufficiency or diabetes mellitus which are asymptomatic following adequatesupplementation, will be eligible.
6. Treatment with chemotherapy, immunotherapy, biologic therapy (except for denosumab andbisphosphonates), or other investigational agents <21 days of enrolment (initiation ofdepletion phase)
7. Palliative radiotherapy within 14 days or less from enrolment.
8. Comorbidity requiring corticosteroid therapy (>10mg prednisone/day or equivalent)within 7 days of enrolment. Physiologic replacement doses are allowed if they are ≤10mg of prednisone/day or equivalent, as long as they are not being administered forimmunosuppressive intent. Inhaled, intranasal or topical steroids are permitted,provided that they are not for treatment of an autoimmune disorder.
9. Significant cardiac disease; New York Heart Association classification for chronicheart failure III-IV, symptomatic coronary artery disease, significant ventriculararrhythmias, myocardial infarction within 6 months, unstable, poorly controlled anginapectoris
10. Active, known or suspected autoimmune disease that has required systemic treatmentwithin the past 2 years (i.e., with use of disease-modifying agents, corticosteroidsor immunosuppressive drugs), except for replacement therapy (e.g., thyroxine, insulin,or physiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency, etc.). Note: corticosteroids given within 24 hours of an imaging study for purposes ofpre-medication in subjects with hypersensitivity to radiologic contrast agents areallowed
11. Serious active infection requiring systemic therapy
12. Subject has completed a course of antibiotics within the four weeks prior toenrollment
13. Subjects, who, in the opinion of the investigator, have predisposing risk factors forrecurrent infections requiring systemic antibiotic treatment (i.e., fistulae,obstructing pulmonary mass, non-healing wound)
14. A known psychiatric or substance abuse disorder that would interfere with thesubject's ability to cooperate with the requirements of the trial
15. Receipt of a live-virus vaccination within 28 days of enrolment. COVID-19 vaccine isnot mandatory. However, patients who have been vaccinated against COVID-19 prior tostudy entry, should have completed the primary series of vaccination (initial twodoses of the vaccine) at least 3 days before enrolment.
16. Known HIV infection, or active infection with hepatitis B or C
17. History of (non-infectious) pneumonitis that required steroids or has current activepneumonitis
18. Known additional malignancy either progressing or requiring active treatment (exceptfor non-melanoma skin cancer, in situ cervical cancer or prostate intraepithelialneoplasia) within the last 2 years.
19. Female subjects who are breastfeeding
20. Known intolerance or hypersensitivity to study drugs
21. Known intolerance or hypersensitivity to oral vancomycin or neomycin
22. History or current evidence of any condition, therapy, or laboratory abnormality thatmight confound the results of the trial, interfere with the subject's participationfor the full duration of the trial, or is not in the best interest of the subject toparticipate, in the opinion of the treating investigator
23. Known inability to orally ingest capsules