This is phase 2 single arm study evaluating the safety and preliminary efficacy of M-CENK adoptive cell therapy and fixed dose of N-803 in combination with gemcitabine in participants with platinum-resistant high-grade ovarian cancer (HGOC).Up to 20 participants will receive M-CENK (IV) and N-803 (SC) in combination with gemcitabine (IV).

Participants will undergo an apheresis procedure for the collection of mononuclear cells (MNCs) at least 1 day prior to Cycle 1 for manufacturing of M-CENK. Starting in Cycle 1, participants will receive gemcitabine and starting in Cycle 2 they will also receive M-CENK and N-803, until no additional M-CENK is available or confirmed PD per iRECIST, unless the participant is potentially deriving benefit per Investigator's assessment.

Participants who complete the study treatment or discontinue study treatment will be followed for survival/disease status every 12 weeks (± 2 weeks) for up to 12 months after the last study treatment or until death, lost to follow-up, or withdrawal of consent.

Inclusion Criteria:

1. ≥18 years and <85 years old.

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

3. Participants must be appropriate for single-agent therapy as the next line of therapy, 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 relapse within 6 months of receiving 1 to 3 platinum-based chemotherapy regimens.

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

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

   • Participants who had received one line of platinum-based therapy must have received at least four cycles of their initial platinum-containing regimen, had a response (complete or partial), and then had PD between 3 and 6 months after their last dose.
   • Participants who had previously received two or three lines of platinum-based therapy must have had PD while receiving the therapy or within 6 months after the last dose.

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

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

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

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

12. Agreement to practice effective contraception for female participants of childbearing potential. Female participants of childbearing potential must agree to use 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 first dose 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) (except Gilbert'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 by Cockcroft-Gault Formula (Appendix C.1)
    • Oxygen saturation: ≥ 90% on room air

16. Participants with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

17. Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification (Appendix B.2). To be 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 required by 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 tumors containing any of the above histologies, or low grade or borderline ovarian tumor.
2. Distant metastasis outside of the abdominopelvic cavity (e.g., central nervous system, pulmonary, osseous, etc.).
3. Have had anti-tumor chemotherapy or other investigational agents within 2 weeks prior to M-CENK cell infusion, or immunotherapy within 4 weeks prior, or those who have not recovered from adverse events due to agents administered more than two weeks prior. The intent of the language is to ensure that anti-tumor chemotherapy or other investigational agents are not administered to participants within the specified window since they can potentially affect M-CENK cell activity. Therefore, the washout period is defined by time from NK cell infusion and not patient enrollment. During eligibility confirmation from the study team is requested to confirm that according to the planned M-CENK cell dosing schedule, the washout period should be completed, based on each drug class.
4. Current bowel obstruction, history of bowel obstruction, or high risk for bowel obstruction (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, or history of other malignancy within 2 years of the first dose of study treatment with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other non-invasive or 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 in permanent discontinuation of therapy (as recommended per product label or consensus guidelines) OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well-controlled on replacement hormones) are excluded.
13. Autoimmune disease: history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [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 Hashimoto thyroiditis are eligible.
14. Systemic corticosteroid therapy (> 10 mg of prednisone or equivalent dose of systemic steroids for at least 4 weeks prior to NK cell infusion). The intent of this language is to ensure that systemic steroids are not administered to participants within the specified window since this can potentially affect NK cell activity. Therefore, the washout period is defined by time from NK cell infusion and not patient enrollment. During eligibility confirmation the study team is requested to confirm that according to the planned NK cell dosing schedule, the washout period should be completed.
15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
16. HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with anti-retroviral agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy.
17. Active uncontrolled hepatitis B or C are ineligible as they are at high-risk of lethal treatment-related hepatotoxicity in the setting of marrow suppression. Known non-infectious pneumonitis or any history of interstitial lung disease.
18. Receipt of a live vaccine within 30 days of start of study treatment. During eligibility confirmation the study team is requested to confirm that according to the 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.