A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC

Inclusion Criteria:

1. Age and gender: 18 and older, all genders
2. Signed written informed consent . Participants must be willing to participate in thestudy and provide written and signed informed consent (ICF) for the study. Participants must be willing and able to complete all study specific procedures andvisits
3. Diagnosis: For NSCLC patients Histologically or cytologically confirmed metastatic or locallyadvanced non-small cell lung cancer not amenable to curative treatment that have aconfirmed progression on anti-PD-1/PDL1 therapy: Subjects may have had a maximum of one prior line of therapy after failure ofanti-PD-1/ Programmed death-ligand 1 (PDL1) therapy Received a platinum basedchemotherapy for non-small cell lung cancer; or, Subjects with a documented activatingmutation {e.g., against epidermal growth factor receptor (EGFR), against rearrangedanaplastic lymphoma kinase (ALK), Proto-oncogene tyrosine-protein kinase (ROS)} musthave received the appropriate targeted therapy. For Melanoma patients Histologically confirmed unresectable or metastatic melanoma notamenable to curative treatment that have a confirmed progression on anti-PD-1/PD-L1therapy: a. Subjects may have had a maximum of one prior line of therapy after failureof anti-PD-1/PDL1 therapy b. Subjects with a documented B-Raf (BRAF) mutation musthave received the appropriate targeted therapy For MSI-H/dMMR patients -Histologically confirmed MSI-H/dMMR metastatic solid tumorsincluding the following indications: colorectal adenocarcinoma, gastricadenocarcinoma, esophageal adenocarcinoma, endometrial carcinoma, ovarian carcinoma,pancreatic ductal adenocarcinoma and urothelial carcinoma that had a confirmedprogression on anti-PD-1/PD-L1-based therapy.
4. Biopsies Patients must agree to study biopsies at two time points: a. Pretreatment andon treatment gut biopsies. b. Pretreatment and on treatment tumor biopsies.
5. Measurable disease by RECIST v1.1.
6. Patient status: a. Eastern Cooperative Oncology Group (ECOG) status of 0-1 b. Liverfunction: Total bilirubin ≤ 2 Upper limit of normal (ULN), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) ≤ 2.5 ULN (or < 5 in case of present livermetastasis) c. Neutrophils ≥ 1,000/mm3, platelets ≥ 100,000/mm3, Hb>8 g/dL d. Serumcreatinine ≤ 1.5 ULN e. International normalized ratio (INR), prothrombin time (PT),and activated partial thromboplastin time (aPTT) ≤1.5x ULN
7. Pregnancy a. Negative urine or serum pregnancy test within 72 hours prior to receivingfirst dose of study procedure in women of childbearing potential. b. Use of aneffective contraceptive method throughout the entire treatment period and up to 6months after the completion of treatment in both males and females of child bearingpotential.

Exclusion Criteria:

1. Medical Conditions : 1.1 History of chronic or active colitis 1.2. Tumor involvement of the esophagus,stomach, small intestine or colo-rectum. Note: not applicable for patients with MSI-Hor dMMR colorectal , gastric or esophageal adenocarcinoma 1.3. Has a current active ora past known additional malignancy within the last 5 years. 1.4. Has an active or a documented history of autoimmune disease that requiredtreatment in the past 2 years. 1.5. Known food allergy to eggs, nuts, peanuts 1.6. Known allergy toneomycin,vancomycin or metronidazole 1.7. Pregnant or breastfeeding women 1.8. Hasknown history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 1.9 Has knownhistory of or is positive for hepatitis B or Hepatitis C.
2. Prior/Concomitant Therapy and medical procedure 2.1 Has ongoing immune-related adverseeffects from previous immunotherapy treatments that are of Grade ≥2, excludingendocrine adverse effects 2.2 Immunosuppressive chronic treatments. Patients treatedwith Prednisone ≤10mg per day may be included. 2.3 Known active bacterial, viral, fungal, mycobacterial, parasitic, or otherinfection (excluding fungal infections of nail beds) or any major episode of infectionrequiring treatment with i.v. antibiotics or hospitalization (relating to thecompletion of the course of antibiotics, except if for tumor fever) within 28 daysprior to the start of Day 1 2.4 Medical condition that requires chronic treatment withantibiotics 2.5 Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1. 2.6 Has received major surgery (within 28 days prior to the start of Cycle 1, Day 1),other than for diagnosis. Patient must have recovered from all surgery-relatedtoxicities. 2.7 Patient has a known intolerance to anti-PD-L1 or anti-PD1.
3. Prior/Concurrent Clinical Study Experience 3.1 Participation in another clinical trialwith anti-neoplastic intervention up to 14 days prior to study entry
4. Other Exclusions 4.1 Any other serious uncontrolled medical condition (includingactive bleeding or non-healing wound) 4.2 Has known psychiatric or substance abusedisorder that would interfere with cooperation with the requirements of the study.