Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer

Inclusion criteria:

1. Subjects must be 18 years or older.

2. Subjects must be willing and able to provide informed consent.

3. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0 or 1.

4. A female participant is eligible to participate if at least one of the followingconditions applies:

5. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1

6. A WOCBP who agrees to follow the contraceptive guidelines in Appendix 1 duringthe treatment period and for at least 3 months after the last dose of studytreatment.

7. Subjects must have measurable disease present as defined by modified RECIST v1.1criterion, and have disease present in the peritoneal cavity or retroperitoneallymph nodes. Disease outside the peritoneal cavity is allowed as long as metastasesare present within the peritoneal cavity or retroperitoneum.

8. Subject tumors must demonstrate at least 1+ TROP2 expression byimmunohistochemistry.

9. Subjects must be at least 3 weeks from last cytotoxic chemotherapy at the time ofstarting lymphodepleting chemotherapy.

10. Subjects must be willing to undergo intraperitoneal port placement and scheduledperitoneal fluid and peripheral blood draws.

11. Subjects must have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of studytreatment.

Table 1. Adequate Organ Function Laboratory Values Systemic Function Test Laboratory Value Hematologic Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥100,000/µL Hemoglobin ≥8.0 g/dL (transfusion is allowed)a Renal Creatinine OR Creatinine clearance (CrCl) by Cockroft-Gault

• 1.5 x ULNb

• 30 mL/min for participants with creatinine > 1.5 x ULNb Hepatic Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubinlevels >1.5 x ULN AST (SGOT) and ALT (SGPT) ≤2.5 x ULN (≤5 x ULN forparticipants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless participate is receiving anticoagulant therapy as long as PTor aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase);AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase);GFR=glomerular filtration rate; ULN=upper limit of normal.

1. Criteria must be met without erythropoietin dependency and without packedred blood cell (pRBC) transfusion within last 2 weeks of the screeningtest. Participants may be on a stable dose of erythropoietin (≥approximately 3 months).

2. Serum creatinine and creatinine clearance (CrCl) should be interpreted andcalculated per institutional standard. Note: This table includes eligibility-defining laboratory valuerequirements for treatment; laboratory value requirements should beadapted according to local regulations and guidelines for theadministration of specific chemotherapies. Inclusion Criteria: Ovarian Cancer:

3. Subjects must have a histology confirming diagnosis of high gradeserous ovarian/peritoneal/fallopian tube cancer with pathologyreviewed at MD Anderson Cancer Center.

4. Subjects must have failed at least two prior lines of chemotherapy (i.e. frontline adjuvant chemotherapy plus one additional line forrecurrent/progressive disease), or have platinumresistant diseasedefined as disease progression on a platinum-containing agent orrecurrence within 180 days of prior dose of a platinum-containingchemotherapeutic regimen.

5. To be eligible, germline/somatic BRCA1/2 mutation carriers shouldhave received prior PARPi therapy. Mesonephric-like adenocarcinoma:

6. A histology confirming diagnosis of mesonephric-like adenocarcinoma (MLA) originating from the female reproductive tract or peritoneallining (including MLA arising from endometriosis) with pathologyreviewed at MD Anderson Cancer Center.

7. Subjects must have failed at least one prior line ofplatinum-containing chemotherapy. Pancreatic Cancer:

8. Subjects with histologically confirmed diagnosis of pancreatic ductaladenocarcinoma or ampullary-type carcinoma

9. Subjects who have progressive disease after receiving initialtreatment with either FOLFIRINOX, and/or a gemcitabine-based therapy

Exclusion Criteria:

1. Pregnant, breastfeeding, or expecting to conceive within theprojected duration of the study, starting with the screening visitthrough 3 months after the last dose of trial treatment. If a WOCBP has a positive urine pregnancy test within 72 hours priorto hospital admission that cannot be confirmed as negative, a serumpregnancy test will be required (see Appendix 1).
2. Has received systemic anti-cancer therapy including investigationalagents within 4 weeks of starting lymphodepleting chemotherapy.
3. Participants must have recovered from all AEs due to previoustherapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy, alopecia, or othernon-relevant AEs may be deemed eligible at the discretion of the PI.If a participant received major surgery, they must have recoveredadequately from the toxicity and/or complications from theintervention prior to starting study treatment.
4. Has received prior radiotherapy within 2 weeks of start of studyintervention. Participants must have recovered from allradiation-related toxicities, not require corticosteroids, and nothave had radiation pneumonitis. A 1-week washout is permitted forpalliative radiation (≤2 weeks of radiotherapy) to non-centralnervous system (CNS) disease.
5. Has received a live vaccine within 30 days prior to the first dose ofstudy drug. Examples of live vaccines include, but are not limitedto, the following: measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), andtyphoid vaccine. Seasonal influenza vaccines for injection are generally killed virusvaccines and are allowed; However, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
6. Is currently receiving another investigational agent or has used aninvestigational device within 4 weeks prior to the first dose ofstudy intervention. Participants who have entered the follow-up phaseof an investigational study may participate as long as it has been 4weeks after the last dose of the previous investigational agent.
7. Diagnosis of immunodeficiency or receiving chronic systemic steroidtherapy (in dosing exceeding 10 mg daily of prednisone equivalent) orany other form of immunosuppressive therapy within 7 days prior tothe first dose of study drug.
8. History of a second malignancy, unless potentially curative treatmenthas been completed with no evidence of malignancy for 2 years. Thetime requirement does not apply to participants who underwentsuccessful definitive resection of basal cell carcinoma of the skin,squamous cell carcinoma of the skin, superficial bladder cancer, insitu cervical cancer, or other in-situ cancers.
9. Known active CNS metastases and/or carcinomatous meningitis.Participants with previously treated brain metastases may participateprovided they are radiologically stable, i.e. without evidence ofprogression for at least 4 weeks by repeat imaging (note that therepeat imaging should be performed during study screening),clinically stable and without requirement of steroid treatment for atleast 14 days prior to first dose of study intervention.
10. Active autoimmune disease that has required systemic treatment in thepast 2 years (i.e. with use of disease modifying agents,corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacementtherapy for adrenal or pituitary insufficiency, etc.) is allowed.
11. History of interstitial lung disease that required steroids or hascurrent pneumonitis/interstitial lung disease.
12. Active infection requiring systemic therapy.
13. Known history of uncontrolled Human Immunodeficiency Virus (HIV)infection. Patients with HIV infection and undetectable viral loadmay participate.
14. Known history of chronic Hepatitis B or Hepatitis C virus infection.
15. Known history of active TB (Bacillus Tuberculosis).
16. History or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interferewith the subject's participation for the full duration of the study,or is not in the best interest of the subject to participate, in theopinion of the treating investigator.
17. Known psychiatric or substance abuse disorders that would interferewith cooperation with the requirements of the trial.
18. Has had an allogenic tissue/solid organ transplant.
19. Clinically significant cardiovascular disease within 12 months fromfirst dose of study intervention, including New York HeartAssociation (NYHA) Class III or IV congestive heart failure, unstableangina, myocardial infarction, cerebral vascular event, or cardiacarrhythmia associated with hemodynamic instability. Note: medicallycontrolled arrhythmia would be permitted.
20. Prolongation of QTcF interval to >480 ms
21. Bleeding or thrombotic disorders or subjects at risk for severehemorrhage. Subject with known deep vein thrombosis/pulmonaryembolism that are under appropriate anti-coagulation treatment areeligible.
22. Radiographic evidence of tumor encasement or invasion of a majorblood vessel, or intra-tumoral cavitation.
23. Active peritonitis or diverticulitis
24. Medical or surgical history that in the treating physician's opinionwould make the subjective not a suitable candidate forintraperitoneal therapy. Examples would include surgically documentedextensive intraperitoneal adhesions or large volume ascites.
25. History of severe hypersensitivity reaction with biologic therapy (e.g. monoclonal antibodies)