A Phase 1b Trial to Evaluate Safety of MB097 in Combination with Pembrolizumab in Melanoma Patients

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Must have primary resistant cutaneous melanoma and have experienced diseaseprogression as defined by RECIST v1.1 after receiving at least 6 weeks of exposureto PD-1/PD-L1 inhibitor therapy, generally correlating with 2 complete cycles ofPD-1/PD-L1 inhibitor therapy.

• Must have histological or cytological confirmation of Stage III (unresectable) orStage IV cutaneous melanoma

• Must have radiographically measurable disease per RECIST v1.1

• Must be at least 18 years of age at time of informed consent

• Must provide written informed consent, according to local guidelines, signed anddated by the patient prior to the performance of any study-specific procedures,sampling, or analysis

• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0or 1 at time of informed consent.

• Must have acceptable organ function, as evidenced by laboratory data prior to firstdose of any study drug

• Female patients must not be lactating or pregnant

• Male patients, and female patients of childbearing potential who are at risk ofpregnancy must agree to use a highly effective method of contraception

• Must have life expectancy ≥12 weeks after the start of any study drug perInvestigator's judgment

• Must be willing and able to comply with the Protocol, scheduled visits, treatmentplan, study restrictions, laboratory tests, contraceptive guidelines, and all otherstudy procedures.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following

• Any treatment for melanoma following the failure of an aPD-1-containing treatment,i.e., no intervening treatments between aPD-1 failure and enrollment into study;

• Prior therapy with any of the following:

• Radiation therapy to target lesions within 6 weeks of the first dose of MB097

• Major invasive surgery, excluding placement of vascular access, within 28 daysof the first dose of any study drug

• Probiotic supplement use within 7 days of the first dose of any study

• LBP use, including FMT, within 6 months of start of therapy with MB097.

• Active, uncontrolled infection requiring systemic antimicrobial, antiviral, orantifungal therapy.

• Active, uncontrolled, symptomatic brain metastases or leptomeningeal metastases

• Ocular, uveal, acral, or mucosal melanoma

• Prior treatment-related toxicities that have not resolved to Grade 2 or less per NCICTCAE v5.0;

• Patients with a history of immune-related colitis may be included if symptoms haveresolved to Grade 1 or less for at least 14 days prior to screening

• Any history of CTCAE v5.0 immune-related toxicity Grade 3 or greater from prior CPIthat is recurrent or steroid-refractory

• Known hypersensitivity to any of the ingredients of the study drug(s) or knownhypersensitivity to vancomycin (oral or IV)

• Significant medical conditions which, in the Investigator's opinion, couldcompromise or interfere with the patient's safety or integrity of the study outcomes

• Severe colitis of any etiology (except colitis associated with treatment with anaPD-1 inhibitor)

• History of another malignancy within 3 years before the first dose of any studydrug, or any evidence of residual disease from a previously diagnosed malignancy

• Clinically significant (i.e., active) cardiovascular disease

• Any clinically significant safety concern related to prior CPI therapy

• Active autoimmune disease that required systemic treatment in the past 2 years priorto screening

• History of investigational agent or device use within 4 weeks prior to the firstdose of study treatment or current participation in a study of an investigationalagent

• History or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the study, interfere with the patient'sparticipation, or, in the opinion of the Investigator, is considered to not be inthe best interest of the patient to participate in the study.