A Phase 2, Open-label, Single-arm Study of Autologous M-CENK Adoptive Cell Therapy and N-803 (IL-15 Superagonist) in Combination with Gemcitabine in Participants with Recurrent Platinum-Resistant High-Grade Ovarian Cancer

Inclusion Criteria:

1. ≥18 years and <85 years old.

2. Able to understand and provide a signed informed consent that fulfills the relevantInstitutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.

3. Participants must be appropriate for single-agent therapy as the next line oftherapy, as determined by the Investigator.

4. Participants must have received prior treatment with bevacizumab.

5. Confirmed diagnosis of platinum-resistant high-grade epithelial ovarian cancer,primary peritoneal or fallopian tube. Platinum-resistant is defined as a relapsewithin 6 months of receiving 1 to 3 platinum-based chemotherapy regimens.

6. Must have at least one lesion that meets the definition of measurable diseasedefined by RECIST v1.1 criteria.

7. Must have received at least one but no more than three prior systemic lines ofanticancer therapy and had progressive disease (PD) while receiving or immediatelyafter receiving the previous therapy. Progression will be calculated from the dateof the last administered dose of platinum based therapy to the date of radiographicimaging that showed evidence of progression.

• Participants who had received one line of platinum-based therapy must havereceived at least four cycles of their initial platinum-containing regimen, hada response (complete or partial), and then had PD between 3 and 6 months aftertheir last dose.

• Participants who had previously received two or three lines of platinum-basedtherapy must have had PD while receiving the therapy or within 6 months afterthe last dose.

8. Participants with germline or somatic BRCA1 or BRCA2 mutations must have receivedprior PARP inhibitor therapy as maintenance or treatment.

9. Must have adequate peripheral venous access on both arms, or be willing to havetemporary vascular access placed for apheresis collection, if deemed necessary bythe Investigator.

10. Must be able to sit or recline with limited movement for approximately 6 hoursduring apheresis procedure.

11. Participants must have been previously tested for FRα. If the test result waspositive, they must have been offered treatment with mirvetuximab soravtansine-gynx.

12. Agreement to practice effective contraception for female participants ofchildbearing potential. Female participants of childbearing potential must agree touse effective contraception for up to 7 months after completion of study treatment.Effective contraception includes surgical sterilization (eg, tubal ligation), orals,injectables, 2 forms of barrier methods (eg, diaphragm), intrauterine devices (IUDs), and hormonal therapy.

13. Eastern cooperative oncology group (ECOG) performance status of ≤ 1.

14. Major surgery must be completed and recovered at least 4 weeks prior to the firstdose of study treatment.

15. Participants must meet the following organ and marrow function as defined below:

• Absolute neutrophil count ≥ 1,000/mm3

• Platelets ≥ 100,000/mm3

• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

• Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (exceptGilbert's or disease-related hemolysis, then < 3 × ULN)

• Albumin ≥ 3.0 g/dL

• Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 40 mL/min/1.73 m2 byCockcroft-Gault Formula (Appendix C.1)

• Oxygen saturation: ≥ 90% on room air

16. Participants with a prior malignancy whose natural history or treatment does nothave the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are eligible for this trial.

17. Known history or current symptoms of cardiac disease, or history of treatment withcardiotoxic agents, should have a clinical risk assessment of cardiac function usingthe New York Heart Association (NYHA) Functional Classification (Appendix B.2). Tobe eligible for this trial, participants should be class 2B or better.

18. Expected survival > 16 weeks.

19. Stated willingness to comply with study procedures.

20. Able to attend required study visits and return for adequate follow-up, as requiredby this protocol.

All inclusion criteria must be answered "yes" for a participant to participate in the trial.

Exclusion Criteria:

In order to participate in the study, participants must not meet any of the following criteria:

1. Participants with clear cell, mucinous, or sarcomatous histology, mixed tumorscontaining any of the above histologies, or low grade or borderline ovarian tumor.

2. Distant metastasis outside of the abdominopelvic cavity (e.g., central nervoussystem, pulmonary, osseous, etc.).

3. Have had anti-tumor chemotherapy or other investigational agents within 2 weeksprior to M-CENK cell infusion, or immunotherapy within 4 weeks prior, or those whohave not recovered from adverse events due to agents administered more than twoweeks prior. The intent of the language is to ensure that anti-tumor chemotherapy orother investigational agents are not administered to participants within thespecified window since they can potentially affect M-CENK cell activity. Therefore,the washout period is defined by time from NK cell infusion and not patientenrollment. During eligibility confirmation from the study team is requested toconfirm that according to the planned M-CENK cell dosing schedule, the washoutperiod should be completed, based on each drug class.

4. Current bowel obstruction, history of bowel obstruction, or high risk for bowelobstruction (in the opinion of the investigator).

5. Poor oral intake requiring parenteral nutrition or dependence on intravenous fluids.

6. Presence or history of ascites.

7. Receiving any other investigational agents.

8. Solid organ transplant (allograft) recipients.

9. Known additional malignancy that is progressing or requires active treatment, orhistory of other malignancy within 2 years of the first dose of study treatment withthe exception of cured basal cell or squamous cell carcinoma of the skin,superficial bladder cancer, carcinoma in situ of the cervix, or other non-invasiveor indolent malignancy, or cancers from which the patient has been disease-free for > 1 year after treatment with curative intent.

10. Known hypersensitivity or anaphylaxis to sulfa-containing study medication(s).

11. Known allergy to dimethyl sulfoxide (DMSO).

12. Prior history of immune-related toxicity during immune therapy that resulted inpermanent discontinuation of therapy (as recommended per product label or consensusguidelines) OR any immune-related toxicity requiring intensive or prolongedimmunosuppression to manage (with the exception of endocrinopathy that iswell-controlled on replacement hormones) are excluded.

13. Autoimmune disease: history of inflammatory bowel disease, including ulcerativecolitis and Crohn's disease, are excluded from this study, as are patients with ahistory of symptomatic disease (e.g., rheumatoid arthritis, systemic progressivesclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [Wegener's granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis). participants with Hashimotothyroiditis are eligible.

14. Systemic corticosteroid therapy (> 10 mg of prednisone or equivalent dose ofsystemic steroids for at least 4 weeks prior to NK cell infusion). The intent ofthis language is to ensure that systemic steroids are not administered toparticipants within the specified window since this can potentially affect NK cellactivity. Therefore, the washout period is defined by time from NK cell infusion andnot patient enrollment. During eligibility confirmation the study team is requestedto confirm that according to the planned NK cell dosing schedule, the washout periodshould be completed.

15. Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

16. HIV-positive participants are ineligible because of the potential forpharmacokinetic interactions with anti-retroviral agents used in this study. Inaddition, these participants are at increased risk of lethal infections when treatedwith marrow-suppressive therapy.

17. Active uncontrolled hepatitis B or C are ineligible as they are at high-risk oflethal treatment-related hepatotoxicity in the setting of marrow suppression. Knownnon-infectious pneumonitis or any history of interstitial lung disease.

18. Receipt of a live vaccine within 30 days of start of study treatment. Duringeligibility confirmation the study team is requested to confirm that according tothe planned NK cell dosing schedule, the washout period should be completed.

All exclusion criteria must be answered "no" for a participant to participate in the trial.