Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Analgesics

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Interleukin-2

Analgesics, Non-Narcotic

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

IP FT516

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

Enoblituzumab

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.

IL-2

Melissa Geller, MD, MS

This is a single center Phase I clinical trial of FT516 administered intraperitoneally (IP) once a week for 3 consecutive weeks for the treatment of recurrent gynecologic cancers. As this is an early 1st in human study and the 1st intraperitoneal infusion of FT516, the safety of FT516 is confirmed prior to adding enoblituzumab as an intravenous infusion approximately 1 week prior to the 1st dose of FT516 and every 3 weeks beginning on Day 22 (1 week after the last dose of FT516). Each dose of FT516 is followed directly by an IP infusion of interleukin-2 (IL-2) to facilitate natural killer (NK) cell survival. A short course of outpatient lymphodepletion chemotherapy is given prior to the 1st dose of FT516.

FT516 is an off the shelf product comprised of allogeneic natural killer (NK) cells, expressing high-affinity non-cleavable CD16 (FT516). Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3 which is highly expressed on ovarian cancer. Based on data showing that within the ovarian cancer tumor microenvironment surface expression of CD16a on NK cells is diminished, the researchers hypothesize that the FT516 cellular product containing a non-cleavable CD16 will bypass the low CD16 expression issue and maximize NK cell cytotoxicity. Enoblituzumab is an Fc optimized humanized IgG1 monoclonal antibody that binds to B7-H3 (CD276). B7-H3 is an inhibitory immune checkpoint molecule that is widely expressed by a number of different tumor types and may play a key role in regulating the immune response. It is therefore hypothesized that the combination of FT516 with enoblituzumab will maximize NK cell cytotoxicity in patients with ovarian cancer.

This study is conducted in two consecutive stages with 5 cohorts. A minimum of 28 days must separate each cohort. Within a 3 patient cohort, a minimum of 14 days must separate the first and second patient. Stage 1 Step 1 uses a fast-track design (1 patient per cohort) with a minimum of 28 days between each patient until one of the following: a) 1st occurrence of a pre-defined adverse event at which point the study moves to Step 2. The cohort size increases from 1 to 3 patients with 2 additional patients added. Escalation in Step 2 continues until the 1st DLT at which point Stage 2 continual reassessment method (CRM) is activated. If Cohort 5 is completed with 10 patients enrolled at the MTD without a DLT, Stage 2 (CRM) is not used. b) The 1st occurrence of a DLT the study moves directly to Stage 2 (CRM) and Step 2 is not used. c) Cohort 5 is completed without a pre-defined AE or a DLT - neither Step 2 nor Stage 2 is used if a total of 10 patients are enrolled in Cohort 5.

FT516 and IL2 With Enoblituzumab for Ovarian Cancer

Intraperitoneal FATE FT516 and Interleukin-2 (IL-2) With Intravenous Enoblituzumab in Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

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

Number of participants experiencing adverse events related to FT516

Number of participants experiencing progression free survival at 6 months from the first dose of FT516

Number of participants experiencing progression free survival at 1 year from the first dose of FT516

Number of participants experiencing overall survival at 6 months from the first dose of FT516

Number of participants experiencing overall survival at 1 year from the first dose of FT516

National Cancer Institute (NCI)

Masonic Cancer Center, University of Minnesota

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.

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

Monotherapy: IP FT516 at 3 x 10^8 Cells/Dose on Day 1, 8, and 15

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

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.

Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6

Highest Dose (MTD) From 1st 3 Levels + IV Enoblituzumab on Day -6

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

No patients were enrolled in 'Safe dose (MTD-1) from 1st 3 levels + IV enoblituzumab on Day -6' or 'Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6 ' Arms

Melissa Geller, MD

Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events

No participants were enrolled in the "Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6" and "Highest Dose (MTD) From 1st 3 Levels + IV Enoblituzumab on Day -6" arms.

Number of Participants Experiencing Adverse Events

Experimental: Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6

No data collected as no participants were on study at 6 months from first dose of FT516 in the "Monotherapy: IP FT516 at 9 x 10\^7 cells/dose on Day 1, 8, and 15" and "Monotherapy: IP FT516 at 9 x 10\^8 cells/dose on Day 1, 8, and 15" arms.

No data collected as no participants were enrolled in the "Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6" and "Highest Dose (MTD) From 1st 3 Levels + IV Enoblituzumab on Day -6" arms.

Number of Participants Experiencing Progression Free Survival

No data collected as no participants were enrolled in the "Safe Dose (MTD-1) From 1st 3 Levels + IV Enoblituzumab on Day -6" and "Highest Dose (MTD) From 1st 3 Levels + IV Enoblituzumab on Day -6" arms.

No data collected as no participants were on study at 1 year from first dose of FT516 for all remaining arms.

Spots Global Cancer Trial Database for FT516 and IL2 With Enoblituzumab for Ovarian Cancer

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