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.
≥18 years and <85 years old.
Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
Participants must be appropriate for single-agent therapy as the next line of therapy, as determined by the Investigator.
Participants must have received prior treatment with bevacizumab.
Participants with clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low grade or borderline ovarian tumor.
Distant metastasis outside of the abdominopelvic cavity (e.g., central nervous system, pulmonary, osseous, etc.).
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.
Current bowel obstruction, history of bowel obstruction, or high risk for bowel obstruction (in the opinion of the investigator).
Single group
Gemcitabine
DrugDose: 800 mg/m2 intravenously (IV) Frequency: administered on Day 1, Day 8, and Day 15 of each cycle (every 4 weeks)
N-803
Biological/VaccineDose: fixed dose of 1.2 mg subcutaneously (SC) Frequency: administered on Day 1 and Day 15 of each cycle starting at Cycle 2 (every 4 weeks) and when the last dose of M-CENK is administered, N-803 will be administered on Days 1 and 15 of the same cycle followed by 3 additional doses, 2 weeks apart (total of 5 N-803 doses).
M-CENK
Biological/VaccineDose: 0.15 to 0.75 × 109 cells per infusion intravenously (IV) Frequency: administered on Day 1 of each cycle as long as M-CENK cells are available.
Evaluate Progression Free Survival (PFS)
Measured by RECIST v1.1 and iRECIST
Evaluate Overall Survival (OS)
Evaluate Objective Response Rate (ORR)
Measured by RECIST v1.1 and iRECIST
Evaluate Duration of Response (DOR)
Measured by RECIST v1.1 and iRECIST
Safety: Evaluate adverse events
Safety: Incidence of clinically significant changes in comprehensive metabolic panel (CMP)
Standard blood chemistry panel made up of 14 separate chemistry measurements so can detect a range of abnormalities in blood sugar, nutrient balance, and liver and kidney health. Each clinical site will use their local laboratory upper limit of normal (ULN) range. The treating investigator will assess each result composing the CMP and determine if each result is within expected normal range or outside of the expected normal range.
Safety: Incidence of clinically significant changes in Hematology blood panel
Blood test checking the levels for White Blood Cell, Red Blood Cell, Platelets, Hemoglobin, Hematocrit, Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils per unit volume. Each clinical site will use their local laboratory upper limit of normal (ULN) range. The treating investigator will assess each component of the Hematology panel and determine if each result is within expected normal range or outside of the expected normal range.
Safety: Incidence of clinically significant changes in Temperature
Temperature measured in either Fahrenheit or Celsius and for any abnormalities. Each site will assess to determine if temperature is within expected normal range or outside of the expected normal range.
Exploratory: Evaluate the number and phenotype of M-CENK cells performed by flow cytometry and mass cytometry (CyTOF).
Exploratory: Characterize the functionality of M-CENK cells as measured by intracellular staining for cytokines, surface marker staining, and assessments of cytotoxicity.
Exploratory: Assess serum cytokine levels before and after M-CENK infusions.
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