4.3 Description 8.4 .4 Pa ckaging and Labeling Information 8. 4.5 Preparation 8. 4. 6 Storage - 8. 4. 7 Stability J1790 / Version 7.0 / December 10, 2020 53 8. 4. 8 Route of Administration - - 8. 4. 9 Subject Care Implications - - 8. 4. 10 Returns and Reconciliation The investigator is responsible for keeping accurate records of the clinical supplies received from BMS or designee, the amount dispensed to, and returned by the subjects and the amount remaining at the conclusion of the trial. Upon completion or termination of the study, all unused and/or partially used investigational product will be destroyed at the site per institutiona l policy. It is the Investigator’s responsibility to arrange for disposal of all empty containers, provided that procedures for proper disposal have been established according to applicable federal, state, local and institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 8.5 Ipilimumab 8.5.1 Agent Accountability The IND S ponsor or the IND Sponsor’s representative shall take responsibility for and J1790 / Version 7.0 / December 10, 2020 54 shall take all steps to maintain appropriate records and ensure appropriate supply, storage, handling, distribution and usage of investigational product in accordance with the protocol and any applicable laws and regulations. At the end of the study period, Bristol - Myers Squibb Company will not continue to supply stu dy drug to subjects/investigators unless the Sponsor - Investigator chooses to extend their study. The investigator is responsible to ensure that the subject receives appropriate standard of care or other appropriate treatment in the independent medical judg ement of the Investigator to treat the condition under study . 8.5.2 Mode of Action Ipilimumab is a fully human immunoglobulin (IgG 1  ) that is specific for the CTLA - 4 antigen expressed on a subset of activated T - cells. CTLA - 4 interaction with the B7 molec ule, one of its ligands expressed on professional antigen presenting cells, can down - regulate T - cell response. Ipilimumab is, thought to act by blocking the interaction of CTLA - 4 with the B7 ligand, resulting in a blockade of the inhibitory effect of T - ce ll activation. The CTLA - 4/B7 creates the interaction. 8.5.3 Description 8.5.4 Packaging and Labeling Information 8.5.5 Preparation J1790 / Version 7.0 / December 10, 2020 55 8.5.6 Storage - 8.5.7 Stability 8.5.8 Route of Administration - 8.5.9 Subject Care Implications J1790 / Version 7.0/ December 10, 2020 56 8.5.10 Returns and Reconciliation The investigator is responsible for keeping accurate records of the clinical supplies received from BMS or designee, the amount dispensed to, and returned by the subjects and the amount remaining at the conclusion of the trial. Upon completion or termination of the study, all unused and/or partially used investigational product will be destroyed at the site per institutional policy. It is the Investigator’s responsibility to arrange for disposal of all empty containers, provided that procedures for proper disposal have bee n established according to applicable federal, state, local and institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 9. CORRELATIVE/SPECIAL STUDIES Research samples will be collected at the discretion of th e PI based on availability of supplies and safety of patient and staff. Sample collection, processing, storage , and shipment instructions will be provided in the Laboratory Manual . 9.1 Tumor Tissue Studies Tumor biopsies will be collected (if a subject ’s tumor is thought to be reasonably safe and easy to biopsy) at baseline and at Cycle 3 (4-6 cores per time point) . If a biopsy was done within 21 days before first dose, archived tissue from this biopsy may be used as baseline sample . Fine needle aspir ation will not be acceptable. Additional optional biopsies may be obtained later in the course of study treatment . Attempts will be made to obtain archived tissue samples from all subjects. Archived FNA biopsy samples do not contain sufficient tissue an d will not be collected. Detailed instructions for tissue collection, processing , storage, and shipment will be provided in the Laboratory Manual . To exp lore the association of OS , PD -L1 positivity, and tumor -infiltrating lymphocyte characteristic s with clinical responses, archived tumor tissue and tumor tissue obtained at baseline and during treatment (Cycle 3) will be compared . PD-L1 expression may predict response to anti - PD-118,19. However, PD -L1 is also upregulated in response to IFN -γ released by infiltrating T cells and could potentially be a predictor of response to any active immunotherapy . Pre - and post - treatment tumor biopsies will also be analyzed for PD -1 expression as well as infiltration of immune cells (effector T cells, Tregs, B cells, dendritic cells, etc). Characterization of immune checkpoint expression as well as immune infiltrates may be predictive of response to therapy and may also give insight into next generati on combinatorial approaches. Preliminary data from a pancreatic cancer immunotherapy study suggests that induction of a T h1and T h17 phenotype at the tumor itself predicts response. Furthermore, upregulation of other inhibitory molecules such as IL-10 and TGF -β may identify other targets for combinatorial strategies . Dependent on availability of paired tissue samples, additional analysis including determination of gene signatures of tumor and immune cells will be performed to look for patterns of response associated with immune activation and changes in the tumor. J1790 / Version 7.0/ December 10, 2020 57 Attempts will be made to obtain archived tissue samples from all subjects . 9.2 Peripheral Blood Mononuclear Cells (PBMCs) Whole blood for isolation of PBMCs will be collected prior to dosing on Day 1 of Cycle s 1, 2, 4, and 6 only during Course 1 . Pre- and post-treatment changes in PBMCs including effector, helper, and regulatory T cells, NK cells, and macrophages through cell phenotyping analysis and gene expression profiling will be measured . In addition, induction of Listeria and mesothelin antigen - specific T cell responses and changes to the T cell epitope repertoire will also be evaluated. The cellular immune responses directed against Lm and mesothelin will be evaluated by using enzyme -linked immunosorbent spot (ELISPOT) and intracellular cytokine staining. Post- treatment expression of PD-1 and other lymphocyte activation markers will be measured as well. These responses will be correlated with OS. PB MCs are isolated and stored fr ozen (liquid nitrogen) until use . Detailed instructions for collection, processing , storage , and shipment are provided in the Laboratory Manual. 9.3 Serum and Plasma Marker Studies Sera will be collected prior to dosing on Day 1 of Cycles 1 -6 only during Course 1 . Additionally, subjects will have whole blood for serum drawn 20 -26 hours post -CRS -207 infusion during Cycles 3-6 for patients in Arm A and during Cycle s 1-6 for patients in Arm B only during Course 1 . Plasma will be collected pr ior to dosing on Day 1 of Cycle s 1, 2, 4, 6, and the EOT evaluation only during Course 1 . Humoral immune responses , including anti-Lm, anti -mesothelin, anti - thyroglobulin and anti -galectin 3 antibodies will be evaluated by using enzyme -linked immunosorbent ass ay (ELISA) . In addition, potential therapeutic targets, biomarkers, and predictors of response and autoimmune toxicity will be evaluated . Sera and plasma are isolated and stored frozen ( -80oC) until use. Detailed instructions for collection, processing , storage , and shipping are provided in the Laboratory Manual. 9.4 Stool and Oral Wash Samples Studies Stool and oral wash specimens (and questionnaire) will be obtained when available. All stool specimens should be collected within 72 hours (and ideally within 24 hours) of the patient's appointment. Baseline specimens may be obtained at Cycle 1 Day 1 ± 30 days of Course 1. Additional samples will be colle cted at Course 1 Cycle 4 Day 1 (± 30 days), Course 1 Cycle 6 Day 1 (± 30 days) and EOT (± 30 days) . Additional samples may be obtained if the patient has any drug-related toxicity or at other timepoints of interest at the discretion of the PI at any point during the trial. Microbial DNA will be isolated from stool and oral wash samples and prepared for 16S V4 sequencing to profile microbial species represented in the gut pre - and post -treatment. In addition, microbial DNA will be subjected to whole geno me metagenomics profiling of microbial species via shotgun sequencing for detailed functional and pathway analysis to determine the change in the species and functions in response to treatment. Further bioinformatics analyses will be performed with these sequencing data to identify candidate microbial biomarkers, and predictors of response. Detailed instructions for stool and oral wash collection, storage , and shipment are provided in the Laboratory Manual. J1790 / Version 7.0/ December 10, 2020 58 9.5 Diagnostic Tissue Samples Tissue, fluid, or blood may be collected from standard of care procedures used to treat or diagnose immune -related toxicities. 9.6 Genomic Analysis Genomic sequencing library construction, whole genome/exome sequencing, whole transcriptome sequencing, mi crobial sequencing, neoepitope prediction, mutation burden, and bioinformatic analysis will be performed either at an on -campus laboratory or at an off -campus sequencing service. All the samples will be de -identified before sending to any laboratory for se quencing. The FASTQ files, BAM files and VCF files will be generated and analyzed. Genomic sequencing data will be stored and computations conducted using a JH IT managed subscription of Azure. Clinical analysis. Several CLIA -certified laboratories now offer molecular profiling of cancer specimens in commercial and noncommercial settings and provide these results to patients and their physicians (e.g. Foundation Medicine, PGDx, Michigan Center for Translational Pathology, or JHU CLIA Laboratories). I t is possible, therefore, that some of our research analyses will be conducted in these CLIA -certified environments. If tissue or cells are evaluated with next generation sequencing strategies to provide a molecular profile of individual cancer specimens in a CLIA -certified facility, these results will be made available to the patient and their physician. Patient confidentiality will be maintained, and the patient’s identity will not be publicly linked to any study results. Researchers may use the data s et generated in the CLIA assay setting to study genetic alterations across a large number of genes important in cancer. Germline mutations are only identified in punitive cancer genes. Researchers will use the data set for exploratory research to study can cer cell heterogeneity. Some of the sequencing data obtained from the NGS strategies will be uploaded to government sponsored databases, such as GEO and dbGAP. The results of the research studies may be published but subjects will not be identified in any publication. If a germline alteration of clinical importance (as judged by the Investigator) to the subject and his or her family members is identified by a CLIA -certified test in the course o f this analysis, attempts will be made in writing to contact the subject and/or family members for genetic counseling referral. J1790 / Version 7.0/ December 10, 2020 59 10. STUDY CALENDAR 10.1 Treatment Arm A Study Procedures Pre-Study Cycle 124 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 EOT26 D1 D2 D425 D1 D2 D425 D927 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 Visit Windows (days)1 -21 to D1 - - ±1 - 2 - ±1 ±1 - 2 - - ±1 - 2 - - ±1 - 2 - - ±1 - 2 - - ±1 +/- 7 CY2 X X Nivolumab2 X X X X X X Ipilimumab2 X X X GVAX Pancreas Vaccine X X CRS -207 X X X X Informed consent X Inclusion/exclusion criteria X Randomization (R) X Demographics X Medical, Cancer, & Con Med History3 X Con Meds, Adverse Events X X X X X X X27 X X X X25 X X X X25 X X X X25 X X X X25 X Physical Exam, ECOG PS4 X X X X27 X X X X X Vitals, Weight, & Height5 X X X X X X27 X X X X X X X X X Hematology, Chemistry6, 12 X X X X27 X X X X X X X X X X X X X Endocrine7, 12 X X X X X X X Urinalysis8, 12 X CD4, Virology9 X Coagulation panel10 X Pregnancy Test11 X X X X X X CA19 -9 12 X X X X X X X J1790 / Version 7.0/ December 10, 2020 60 Study Procedures Pre-Study Cycle 124 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 EOT26 D1 D2 D425 D1 D2 D425 D927 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 ECG13 X CT/MRI, RECIST/irRC14 X X X Vaccine Site Reactions15 X X Whole blood for PBMC16, 29 X X X X Whole blood for plasma16, 29 X X X X Serum16, 29 X X X X X X X X X X Stool , Oral Wash Samples17, 29 X X X X Microbiome Questionnaire17 X X X X HLA18 X Archival Tissue19, 29 X Tumor Biopsies20, 29 X X Antibiotics21,22 X28 X28 Blood sample for CRS -207 testing23 X In order to minimize the need for research -only in -person visits, telemedicine visits may be substituted for in person clinical trial visits or portions of clinical trial visits where determined to be appropriate and where determined by the investigator not to increase the part icipants ris ks. Prior to initiating telemedicine for study visits the study team will explain to the participant, what a telemedicine visit entails an d confirm that the study participant is in agreement and able to proceed with this method. Telemedicine acknowledgemen t will be obtained in accordance with the Guidance for Use of Telemedicine in Research. In the event telemedicine is not deemed feasible, the study visit will proceed as an in -person visit. Telemedicine visits will be conducted using HIPAA compliant method approved by the Health System and within licensing restrictions. 1: If necessary, a scheduled cycle may be delayed for up to 1 week. Longer delays to be approved by the IND Sponsor or Protocol Chair. 2: Order of administration is CY, Nivolumab, and t hen Ipilimumab. Subjects should be observed for a minimum of 30 minutes between each infusion . 3: Cancer history includes: primary site of cancer, gross location of primary tumor, secondary sites of cancer, histology, histo logic grade, date of initial diagnosis, date of metastatic diagnosis, prior cancer therapy regimens. 4: Complete physical examination and assessment of ECOG PS will be completed at baseline; focused physical examinations and asse ssment of ECOG PS will be conducted thereafter. Day 1 Physi cal examination and ECOG status may be done up to 1 day prior to dosing. J1790 / Version 7.0/ December 10, 2020 61 5: Blood pressure, pulse, and temperature are required as indicated. Weight and pulse oximetry will be obtained at baseline and prior to each cycle. Height will be taken at or prior to screening only. Vitals should be collected prior to CY administration and prior to and after GVAX pancreas vaccine administration. Nivolumab: vitals will be collected prior to and at the end of the infusion (-5/+ 15 minutes) . Ipilimumab: vitals will be collected prior to and at the end of the infusion (-5/+ 15 minutes) . CRS -207: vital signs will be obtained prior to and then every 30 minutes (± 15 minutes) during infusion and every hour ( -5/+ 15 minutes) during post -infusion follow -up. Subjects will be observed for at least 4 hours after each CRS -207 infusion. Subjects who are not stable enough to be released at 4 hours after infusion should continue to be monitored until stable. Pre sence of f ever alone does not indicate subject is not clinically stable. 6: Clinical hematology: CBC with differential ANC, ALC, AEC, and platelet count; serum chemistry: sodium, potassium, chloride, b icarbonate, glucose, BUN, creatinine, ALT, AST, alkaline phospha tase, total bilirubin, direct bilirubin, amylase, total protein, albumin, calcium, magnesium, and phosphate. LDH at baseline only. Required labs on Day 2 only after CRS -207 dosing: Any unexpected Grade 3 or greater laboratory abnormalities should be repeat ed within 24 -72 hours. Grade 3 or greater creatinine, AST, ALT, and bilirubin should be repeated within 24 -72 hours as well. 7: TSH (Total T3 and free T4 if TSH abnormal and clinically indicated ). 8: Bilirubin, blood, glucose, ketones, leukocytes, nitr ite, pH, color, protein, RBC and WBC count, and specific gravity. 9: Virology screen: HIV antibody, hepatitis B surface antigen and hepatitis C antibody; additional virology may also be evaluate d. Subjects who are hepatitis C antibody positive and confirm ed negative viral load at screening will be allowed to enroll. 10: Coagulation panel: D -dimer, fibrinogen, international normalized ratio of prothrombin time, APTT 11: Pregnancy tests will be administered to WOCBP: serum pregnancy test is required at screening; urine pregnancy tests are requi red before doses on Day 1 of dosing weeks. 12: Labs may be collected within a window of up to 3 days prior to dosing. Blood draws must not be collected from a central line for at least 4 days after infusion of CRS -207. 13: ECG should be performed at baseline. 14: Spiral CT of thorax, abdomen and pelvis (and other imaging studies as clinically indicated to evaluate suspe cted sites of metastatic disease). If a subject cannot have a CT scan (e.g., allergy to contrast dye), an MRI should be performed. 3-D CT scans and RECIST reads will not be used to determine eligibility at baseline. On study r adiologic evaluations and tumo r measurements (RECIST and irRC per Appendix C and Appendix D ) will be performed every 10 weeks (± 1 week; starting from the date of first treatment) including the EOT evaluation (± 4 weeks). If the EOT visit occurs early, scans do not need to be repeated if one has been done within the past 6 weeks. Weeks are in reference to calendar week and should not be adjusted due to dosing delays. 15: Injection -site reactions will be evaluated on Day 4 after GVAX pancreas vaccinations by phone or email. 16: Up to 120 mL of whole blood for PB MC isolation may be drawn up to 72 hours prior to dosing and must be processed by sponsor -qualified operators within 6 hours of collection and stored in liquid nitrogen . Approximately 20 mL of whole blood for plasma collection wil l be drawn as indicated. Approximately 5.0 mL of blood for serum for immune monitoring will be drawn as indicated. Day 3 blood draws (after CRS -207 only) should be taken between 20 and 26 hours after start of dosing. Collection of whole blood for isolatio n of PBMCs, plasma, and serum will only be drawn during Course 1. 17: Stool and oral wash specimens (and questionnaire) will be obtained when available. All stool specimens should be collected within 72 hours (and ideally within 24 hours) of the patient's appointment. Baseline specimens may be obtained at Cycle 1 Day 1 ± 30 days of Course 1. Additional samples will be collected at Course 1 Cycle 4 Day 1 (± 30 days), Course 1 Cycle 6 Day 1 (± 30 days) , and EOT (± 30 days) . Additional samples may be obtained J1790 / Version 7.0 / December 10, 2020 62 if the patient has any drug - related toxicity or at other timepoints of interest at the discretion of the PI at any point during the trial . Detailed instructions for stool and oral wash collection and shipment are provided in the Laboratory Manual. 1 8 : HLA - typing to include HLA class I type A and B, low resolution. HLA typing is only done during the first course of study treatmen t. 19 : Attempts to obtain surgical or biopsy archival tumor samples will be made for every subject until the sample is obtained or documentation that the sample cannot be obtained. Detailed instructions for tissue collection, processing and shipment are provided in the Laborator y Manual. 20 : Tumor biopsies to be taken (if a subject’s tumor is thought to be reasonably safe and easy t o biopsy) at baseline and at Cycle 3 (4 - 6 cores per timepoint). If a biopsy was done within 21 days before first dose, archived tissue from this biopsy may be used as baseline sample. The Cycle 3 biopsy has a ± 1 week window. Additional optional biopsies may be obtained later in the course of study treatment. Fine needle aspiration will not be acceptable. Biopsies will only be collected during the first course of study treatment. Detailed instructions for tissue collection, processing and shipment are prov ided in the Laboratory Manual. 2 1 - - 2 2 23: Blood for CRS - 207 culture will be collected at EOT (or within 4 weeks of the last dose of antibiotics if patients do not co mplete 6 cycles of treatment) to assess clearance of CRS - 207. After last dose of CRS - 207 , blood will continue to be collected for CRS - 207 culture at 3, 6, 9, and 12 months from last dose of CRS - 207 (+/ - 1 week window for each collection). 2 4 : Cycle 1 Day 1 evaluations do not need to be repeated if they were conducted within 3 days of the pre - study evaluations. The additional course(s) may start as early as 3 weeks (+7 days) from last dose of previous course . 2 5 : Day 4 and 9 (± 1 day) adverse event assessments may be conducted by telephone or email. 2 6 : Subjects will return to the study site for an EOT evaluation. EOT follow - up will occur 28 (±7) days after the final dose. NOTE: CT scan assessment at EOT will occur 28 days (± 4 weeks) after the final dose. If the EOT visit occurs early (or if the patient cannot return due to disease progression) , an assessment for AEs should be made by telephone or email on day 28 (±1) after last study dose. Subjects who discontinue from treatment should be contacted every three months (+/ - 2 weeks) to monitor overall survival. Information of other cancer therapies after discontinuation from the study treatment will be collected as well. Subjects who discontinue treatment should be contacted by telephone or email at 10 0 days (+ 14 day reporting window) to assess for treatment related toxicities that occur in the follow - up period. 2 7 : The firs t 6 subjects randomized to Arm A will return to the study site at Cycle 2, Day 9 for a focused physical examination, assessment of ECOG status, vitals, labs, concomitant medications and adverse events during Course 1 only . 28: Site personnel will contact the subject by telephone (prior to and within 3 days after completion) to facilitate complianc e with antibiotic treatment and document in source. 29: Research samples will be collected at the discretion of the PI based on availability of supplies and safety of patient and st aff. J1790 / Version 7.0/ December 10, 2020 63 10.2 Treatment Arm B Study Procedures Pre-Study Cycle 123 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 EOT25 D1 D2 D3 D9 D1 D2 D3 D924 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 Visit Windows (days)1 -21 to D1 - - - +1 - 2 - - ±1 - 2 - - ±1 - 2 - - ±1 - 2 - - ±1 - 2 - - ±1 +/- 7 Nivolumab2 X X X X X X Ipilimumab2 X X X CRS -207 X X X X X X Informed consent X Inclusion/ exclusion criteria X Randomization (R) X Demographics X Medical, Cancer, & Con Med History3 X Con Meds, Adverse Events X X X X24 X X X X24,26 X X X X24 X X X X24 X X X X24 X X X X24 X Physical Exam, ECOG PS4 X X X X26 X X X X X Vitals, Weight, & Height5 X X X X X X26 X X X X X X X X X Hematology, Chemistry6, 12 X X X X X X X X X X X X X X X X X X X X Endocrine7, 12 X X X X X X X Urinalysis8, 12 X CD4, Virology9 X Coagulation panel10 X Pregnancy Test11 X X X X X X CA19 -9 12 X X X X X X X ECG13 X CT/MRI, RECIST/irRC14 X X X Whole blood for PBMC15, 28 X X X X Whole blood for plasma15, 28 X X X X J1790 / Version 7.0/ December 10, 2020 64 Study Procedures Pre-Study Cycle 123 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 EOT25 D1 D2 D3 D9 D1 D2 D3 D924 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 D1 D2 D3 D9 Serum15, 28 X X X X X X X X X X X X Stool , Oral Wash Samples16, 28 X X X X Microbiome Questionnaire16 X X X X HLA17 X Archival Tissue18, 28 X Tumor Biopsies19, 28 X X Antibiotics20,21 X27 X27 Blood sample for CRS -207 testing22 X In order to minimize the need for research -only in -person visits, telemedicine visits may be substituted for in person clinical trial visits or portions of clinical trial visits where determined to be appropriate and where determined by the investigator not to increas e the participants risks. Prior to initiating telemedicine for study visits the study team will explain to the participant, what a telemedicine visit entails an d confirm that the study participant is in agreement and able to proceed with this method. Telem edicine acknowledgement will be obtained in accordance with the Guidance for Use of Telemedicine in Research. In the event telemedicine is not deemed feasible, the study visit will proceed as an in -person visit. Telemedicine visits will be conducted using HIPAA compliant method approved by the Health System and within licensing restrictions. 1: If necessary, a scheduled cycle may be delayed for up to 1 week. Longer delays to be approved by the IND Sponsor and/or Protocol Chair. 2: Order of administration is Nivolumab followed by Ipilimumab. Subjects should be observed for a minimum of 30 minutes between each infusion. 3: Cancer history includes: primary site of cancer, gross location of primary tumor, secondary sites of cancer, histology, hi stologic grade, date of initial diagnosis, date of metastatic diagnosis, prior cancer therapy regimens. 4: Complete physical examination and assessment of ECOG PS will be completed at baseline; focused physical examinations and asse ssment of ECOG PS will b e conducted thereafter. Day 1 Physical examination and ECOG status may be done up to 1 day prior to dosing. 5: Blood pressure, pulse, and temperature are required as indicated. Weight and pulse oximetry will be obtained at baseline and prior to each cyc le. Height will be taken at or prior to screening only. Nivolumab: vitals will be collected prior to and at the end of the infusion (-5/+ 15 minutes) . Ipilimumab: vitals will be collected prior to and at the end of the infusion (-5/+ 15 minutes) . CRS -207: vital signs will be obtained prior to and then every 30 minutes (± 15 minutes) during infusion and every hour ( -5/+ 15 minutes) during post -infusion follow -up. Subjects will be observed for at least 4 hours after J1790 / Version 7.0/ December 10, 2020 65 each CRS -207 infusion. Subjects who are no t stable enough to be released at 4 hours after infusion should continue to be monitored until stable. Presence of fever alone does not indicate subject is not clinically stable. 6: Clinical hematology: CBC with differential ANC, ALC, AEC, and platelet co unt; serum chemistry: sodium, potassium, chloride, bicarbonate, glucose, BUN, creatinine, ALT, AST, alkaline phosphatase, total bilirubin, direct bilirubin, amylase, total protein, albumin, calcium, magnesium, and phosphate. LDH at baseline only. Required labs on Day 2 only after CRS -207 dosing: Any unexpected Grade 3 or greater laboratory abnormalities should be repeated within 24 -72 hours. Grade 3 or greater creatinine, AST, ALT, and bilirubin should be repeated within 24 -72 hours as well. 7: TSH (Total T3 and free T4 if TSH abnormal and clinically indicated ). 8: Bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, color, protein, RBC and WBC count, and specific gravity. 9: Virology screen: HIV antibody, hepatitis B surface antigen and hepatit is C antibody; additional virology may also be evaluated. Subjects who are hepatitis C antibody positive and confirmed negative viral load at screening will be allowed to enroll. 10: Coagulation panel: D -dimer, fibrinogen, international normalized ratio o f prothrombin time, APTT 11: Pregnancy tests will be administered to WOCBP: serum pregnancy test is required at screening; urine pregnancy tests are requi red before doses on Day 1 of dosing weeks. 12: Labs may be collected within a window of up to 3 days prior to dosing. Blood draws must not be collected from a central line for at least 4 days after infusion of CRS -207. 13: ECG should be performed at baseline. 14: Spiral CT of thorax, abdomen and pelvis (and other imaging studies as clinically indicated to evaluate suspected sites of met astatic disease). If a subject cannot have a CT scan (e.g., allergy to contrast dye), an MRI should be performed. 3-D CT scans and RECIST reads will not be used to determine eligibility at baseline. On study r adiologic evaluations and tumor measurements (RECIST and irRC per Appendix C and Appendix D ) will be performed every 10 weeks (± 1 week; starting from the date of first treatment ) including the EOT evaluation (± 4 weeks). If the EOT visit occurs early, scans do not need to be repeated if one has been done within the past 6 weeks. Weeks are in reference to calendar week and should not be adjusted due to dosing delays. 15: Up to 120 mL of whole blood for PBMC isolation may be drawn up to 72 hours prior to dosing and must be processed by sponsor -qualified operators within 6 hours of collection and stored in liquid nitrogen . Approximately 20 mL of whole blood for plasma collection will be drawn as indicated. Approximately 5.0 mL of blood for serum for immune monitoring will be drawn as indicated. Day 3 blood draws should be taken between 20 and 26 hours after start of dosing. Collection of whole blood for isolation of PBMCs, plasma, and serum will only be drawn during Course 1. 16: Stool and oral wash specimens (and questionnaire) will be obtained when available. All stool specimens should be collected within 72 hours (and ideally within 24 hours) of the patient's appointment. Baseline specimens may be obtained at Cycle 1 Day 1 ± 30 days of Course 1. Additional samples will be collected at Course 1 Cycle 4 Day 1 (± 30 days), Course 1 Cycle 6 Day 1 (± 30 days) , and EOT (± 30 days) . Additional samples may be obtained if the patient has any drug-related toxicity or at other timepoints of interest at the discretion of the PI at any point during the trial. Detailed instructions for stool and oral wash collection and shipment are provided in the Laboratory Manual. 17: HLA -typing to include HLA class I type A and B, low resolution. HLA typing is only done during the first course of study treatment. 18: Attempts to obtain surgical or biopsy archival tumor samples will be made for every subject until the sample is obtained or documentation that th e sample cannot be obtained. Detailed instructions for tissue collection, processing and shipment are provided in the Laborator y Manual. 19: Tumor biopsies to be taken (if a subject’s tumor is thought to be reasonably safe and easy to biopsy) at baseline and at Cycle 3 (4-6 cores per timepoint). If a biopsy was done within 21 days before first dose, archived tissue from this biopsy may be used as baseline sample. The Cycle 3 biopsy has a ± 1 week window. Additional optional biopsies may be obtained later in the course of study treatment. Fine needle aspiration will not be acceptable. J1790 / Version 7.0 / December 10, 2020 66 Biopsies will only be collected during the first course of study treatment. Detailed instructions for tissue collection, processing and shipment are provided in the Laboratory Manual. 2 0 2 1 - 22: Blood for CRS - 207 culture will be collected at EOT (or within 4 weeks of the last dose of antibiotics if patients do not complete 6 cycl es of treatment) to assess clearance of CRS - 207. After last dose of CRS - 207, blood will continue to be collected for CRS - 207 culture at 3, 6, 9, and 12 months from last dose of CRS - 207 (+/ - 1 week window for each collection). 2 3 : Cycle 1 Day 1 evaluations do not need to be repeated if they were conducted within 3 days of the pre - study evaluations. The additional course(s) may start as early as 3 weeks (+7 days) from last dose of previous course . 2 4 : Day 9 (± 1 day) adverse event assessments may be conducted by telephone or email. 2 5 : Subjects will return to the study site for an EOT evaluation. EOT follow - up will occur 28 (±7) days after the final dose. NOTE: CT scan assessment at EOT will occur 28 days (± 4 weeks) after the final dose. If the EOT visit occu rs early (or if the patient cannot return due to disease progression) , an assessment for AEs should be made by telephone or email on day 28 (±1) after last study dose. Subjects who discontinue from treatment should be contacted every three months (+/ - 2 we eks) to monitor overall survival. Information of other cancer therapies after discontinuation from the study treatment will be collected as well. Subjects should be contacted by telephone or email at 100 days (+ 14 day repo rting window) to assess for treat ment related toxicities that occur in the follow - up period. 2 6 : The first 6 subjects randomized to Arm B will return to the study site Cycle 2 , Day 9 for a focused physical examination, assessment of ECOG status, vitals, labs, concomitant medications and a dverse events during Course 1 only . 27: Site personnel will contact the subject by telephone (prior to and within 3 days after completion) to facilitate compliance with antibiotic treatment and document in source. 28: Research samples will be collected at the discretion of the PI based on availability of supplies and safety of patient and staff.