FT516 and IL2 With Enoblituzumab for Ovarian Cancer

NCT ID: NCT04630769

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-02
• Study Completion Date: 2022-01-01

Brief Summary

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.

Detailed Description

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.

Conditions

Ovarian Cancer; Fallopian Tube Adenocarcinoma; Primary Peritoneal Cavity Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

IP FT516

Intervention Type: 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

IL-2

Intervention Type: DRUG

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 3 x 10^8 cells/dose on Day 1, 8, and 15

Group Type: EXPERIMENTAL

IP FT516

Intervention Type: 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

IL-2

Intervention Type: DRUG

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 10^8 cells/dose on Day 1, 8, and 15

Group Type: EXPERIMENTAL

IP FT516

Intervention Type: 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

IL-2

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

IP FT516

Intervention Type: 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

Enoblituzumab

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6

Group Type: EXPERIMENTAL

IP FT516

Intervention Type: 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

Enoblituzumab

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Interleukin-2

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Geller, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P01CA111412

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2020LS001

Identifier Type: -

Identifier Source: org_study_id