Description:
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.
Title
- Brief Title: FT516 and IL2 With Enoblituzumab for Ovarian Cancer
- Official Title: Intraperitoneal FATE FT516 and Interleukin-2 (IL-2) With Intravenous Enoblituzumab in Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Clinical Trial IDs
- ORG STUDY ID:
2020LS001
- NCT ID:
NCT04630769
Conditions
- Ovarian Cancer
- Fallopian Tube Adenocarcinoma
- Primary Peritoneal Cavity Cancer
Interventions
Drug | Synonyms | Arms |
---|
IP FT516 | | Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6 |
Enoblituzumab | | Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6 |
IL-2 | Interleukin-2 | Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Monotherapy: IP FT516 at 9 x 10^7 cells/dose on Day 1, 8, and 15 | Experimental | | |
Monotherapy: IP FT516 at 3 x 10^8 cells/dose on Day 1, 8, and 15 | Experimental | | |
Monotherapy: IP FT516 at 9 x 10^8 cells/dose on Day 1, 8, and 15 | Experimental | | |
Safe dose (MTD-1) from 1st 3 levels + IV enoblituzumab on Day -6 | Experimental | | - IP FT516
- Enoblituzumab
- IL-2
|
Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6 | Experimental | | - IP FT516
- Enoblituzumab
- IL-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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants experiencing Dose Limiting Toxicity (DLT) events |
Time Frame: | 28 Days Post FT516 infusion |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | Number of participants experiencing progression free survival |
Time Frame: | 6 months from the first dose of FT516 |
Safety Issue: | |
Description: | Number of participants experiencing progression free survival at 6 months from the first dose of FT516 |
Measure: | Number of participants experiencing progression free survival |
Time Frame: | 1 year from the first dose of FT516 |
Safety Issue: | |
Description: | Number of participants experiencing progression free survival at 1 year from the first dose of FT516 |
Measure: | Number of participants experiencing overall survival |
Time Frame: | 6 months from the first dose of FT516 |
Safety Issue: | |
Description: | Number of participants experiencing overall survival at 6 months from the first dose of FT516 |
Measure: | Number of participants experiencing overall survival |
Time Frame: | 1 year from the first dose of FT516 |
Safety Issue: | |
Description: | Number of participants experiencing overall survival at 1 year from the first dose of FT516 |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Masonic Cancer Center, University of Minnesota |
Last Updated
April 13, 2021