Clinical Trials /

FT516 and IL2 With Enoblituzumab for Ovarian Cancer

NCT04630769

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
IP FT516Highest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6
EnoblituzumabHighest dose (MTD) from 1st 3 levels + IV enoblituzumab on Day -6
IL-2Interleukin-2Highest 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

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