FT516 and IL2 With Enoblituzumab for Ovarian Cancer | NCT04630769

NCT04630769

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
P01CA111412	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Label	Type	Intervention Names
Monotherapy: IP FT516 at 9 x 10^7 cells/dose on Day 1, 8, and 15	Experimental	Drug: IP FT516 Drug: IL-2
Monotherapy: IP FT516 at 3 x 10^8 cells/dose on Day 1, 8, and 15	Experimental	Drug: IP FT516 Drug: IL-2
Monotherapy: IP FT516 at 9 x 10^8 cells/dose on Day 1, 8, and 15	Experimental	Drug: IP FT516 Drug: IL-2
Safe dose (MTD-1) from 1st 3 levels + IV enoblituzumab on Day -6	Experimental	Drug: IP FT516 Drug: Enoblituzumab Drug: IL-2
Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6	Experimental	Drug: IP FT516 Drug: Enoblituzumab Drug: IL-2

Name	Type	Description	Arm Group Labels	Other Names
IP FT516	Drug	FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events	DLT is defined as any treatment emergent toxicity at least possibly related to the study treatment meeting one of the following criteria based on CTCAE v5 within 28 days (14 days for ascites) of the 1st FT516 infusion (for Cohort 4 and 5, DLT assessment starts with enoblituzumab and continues for 28 days after 1st FT516): Grade 3 organ toxicity (pulmonary, hepatic, renal, or neurologic) not pre-existing and lasting more than 72 hours , Any non-hematologic Grade 4 or 5 toxicity, Neutrophil count decreased ≥ Grade 4 that persists at Day 28 despite use of growth factor support ,Grade 3 abdominal pain lasting more than 4 consecutive days and not controlled by standard analgesics, Grade 3 or greater ascites within 14 days after FT516 administration in patients who had no ascites or Grade 1 ascites at enrollment and is not attributable to disease progression	28 Days Post FT516 infusion
Number of Participants Experiencing Adverse Events	Number of participants experiencing adverse events related to FT516	28 days after first dose of FT516 or 28 days after last dose of Enoblituzumab (arm 4 and 5 only)

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Experiencing Progression Free Survival	Number of participants experiencing progression free survival at 6 months from the first dose of FT516	6 months from the first dose of FT516
Number of Participants Experiencing Progression Free Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer meeting one of the following minimal prior treatment requirement (no limit to the maximum number of prior treatments):
Platinum Resistant: may receive FT516 as 2nd line (as 1st salvage therapy) with platinum resistant is defined as disease that has responded to initial chemotherapy but demonstrates recurrence within a relatively short period of time (< 6 months) following the completion of treatment.
Platinum Sensitive: may receive FT516 as 3rd line therapy (as 2nd salvage therapy) with platinum sensitive is defined as the recurrence of active disease in a patient who has achieved a documented response to initial platinum-based treatment and has been off therapy for an extended period of time (≥ 6 months).
Measurable disease per modified Response Evaluation Criteria in Solid Tumors, v1.1 within the abdomen and pelvis assess within 42 days of the 1st FT516 infusion. Extra-peritoneal disease is permitted; however each lesion must be < 5 cm at the largest diameter.
At least 18 years of age
GOG Performance Status 0, 1, or 2
Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:
Hematologic: platelets ≥ 75,000 x 10^9/L and hemoglobin ≥ 9 g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10^9/L, unsupported by G-CSF or granulocytes
Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m^2 per current institutional calculation formula
Hepatic: AST and ALT ≤ 3 x upper limit of institutional normal
Pulmonary Function: Oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function >50% corrected DLCO and FEV1
Cardiac Function: LVEF ≥ 40% by echocardiography, MUGA, or cardiac MRI; no clinically significant cardiovascular disease including any of the following: stroke or myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher
Agrees to the placement of an intraperitoneal catheter before the 1st dose of study directed drug (chemotherapy or enoblituzumab - Cohort 4 and 5) and remains in place through Day 36 or longer if retreatment is planned
Agrees to undergo a tumor biopsy if feasible at the time the catheter is placed and removed - Accessible tumor for biopsy is not required for eligibility.
Washout period of at least 14 days after any standard of care tumor directed therapy prior to the first dose of investigational product (FT516 for Levels 1-3 or enoblituzumab for Levels 4-5)
If history of brain metastases must be stable for at least 3 months after treatment - A brain CT scan or MRI is only be required in subjects with known brain metastases at the time of enrollment or in subjects with clinical signs or symptoms suggestive of brain metastases
Must agree to and sign the consent for the companion Long-Term Follow-Up study (CPRC #2020LS072) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product
Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria:

Pregnant or breastfeeding or planning on becoming pregnant in the next 6 months. Woman of childbearing potential who still have a uterus and ovaries, must agree to use at effective contraception and must have a negative pregnancy test within 14 days of study enrollment.
Any known condition that requires systemic immunosuppressive therapy (> 5mg prednisone daily or equivalent) during the FT516 dosing period (3 days before the 1st dose through 14 days after the last dose) - topical and inhaled steroids are permitted.
Active autoimmune disease requiring systemic immunosuppressive therapy
History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
Uncontrolled bacterial, fungal or viral infections with progression of clinical symptoms despite therapy
Receipt of any investigational agent within 28 days prior to the first dose of investigational product (FT516 for Levels 1-3 or enoblituzumab for Levels 4-5)
Live vaccine <6 weeks prior to start of lympho-conditioning
Known allergy to the following FT516 components: albumin (human) or DMSO
Any history of prior enoblituzumab administration
Known history of HIV positivity or active hepatitis C or B - chronic asymptomatic viral hepatitis is allowed
Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to patient

Name	Affiliation	Role
Melissa Geller, MD, MS	Masonic Cancer Center, University of Minnesota	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota, Masonic Cancer Center		Minneapolis	Minnesota	55455	United States

Arm/Group Information

ID	Title	Description
FG000	Monotherapy: IP FT516 at 9 x 10^7 Cells/Dose on Day 1, 8, and 15	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.
FG001	Monotherapy: IP FT516 at 3 x 10^8 Cells/Dose on Day 1, 8, and 15	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.
FG002	Monotherapy: IP FT516 at 9 x 10^8 Cells/Dose on Day 1, 8, and 15	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.
FG003	Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation Enoblituzumab: Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3 which is highly expressed on ovarian cancer. Enoblituzumab at 15 mg/kg IV, one day before lymphodepleting chemotherapy IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.
FG004	Highest Dose (MTD) From 1st 3 Levels + IV Enoblituzumab on Day -6	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation Enoblituzumab: Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3 which is highly expressed on ovarian cancer. Enoblituzumab at 15 mg/kg IV, one day before lymphodepleting chemotherapy IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Monotherapy: IP FT516 at 9 x 10^7 Cells/Dose on Day 1, 8, and 15	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events

DLT is defined as any treatment emergent toxicity at least possibly related to the study treatment meeting one of the following criteria based on CTCAE v5 within 28 days (14 days for ascites) of the 1st FT516 infusion (for Cohort 4 and 5, DLT assessment starts with enoblituzumab and continues for 28 days after 1st FT516): Grade 3 organ toxicity (pulmonary, hepatic, renal, or neurologic) not pre-existing and lasting more than 72 hours , Any non-hematologic Grade 4 or 5 toxicity, Neutrophil count decreased ≥ Grade 4 that persists at Day 28 despite use of growth factor support ,Grade 3 abdominal pain lasting more than 4 consecutive days and not controlled by standard analgesics, Grade 3 or greater ascites within 14 days after FT516 administration in patients who had no ascites or Grade 1 ascites at enrollment and is not attributable to disease progression

Posted

Count of Participants

Participants

28 Days Post FT516 infusion

ID	Title	Description
OG000	Monotherapy: IP FT516 at 9 x 10^7 Cells/Dose on Day 1, 8, and 15

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Monotherapy: IP FT516 at 9 x 10^7 Cells/Dose on Day 1, 8, and 15	IP FT516: FT516 is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation IL-2: IL-2 at 6 Million IU (3 Million IU/m2 if patient weight is <45 kg) is administered IP in 50 cc of room temperature D5W via peritoneal catheter directly after the FT-516 infusion is completed. Immediately following the IL-2, an additional 100 cc D5W flush is infused into the peritoneal cavity through the peritoneal catheter as rapidly as possible.

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases

ID	Term
D007378	Interleukins
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides