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Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

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Ovarian Neoplasms

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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.

Number of Participants Experiencing Overall Survival

Overall Study

Digestive System Diseases

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Fallopian Tube Cancer

Mitoguazone

Level -1: IP FT538 monotherapy 5 x 10\^7 cells/dose Level 1: IP FT538 monotherapy 1 x 10\^8 cells/dose Level 2: IP FT538 monotherapy 3 x 10\^8 cells/dose Level 3: IP FT538 monotherapy 1 x 10\^9 cells/dose Level 4: IP FT538 monotherapy 1.5 x 10\^9 cells/dose

Level 5: IP FT538 at the safe dose (MTD-1) + Enoblituzumab Level 6: IP FT538 at the highest dose (MTD) + Enoblituzumab

FT538 IP at assigned dose level on Day 1, Day 8, and Day 15.

FT538

Enoblituzumab 15 mg/kg IV begin on Day -6 and continuing once every 3 weeks beginning on Day 22 until disease progression or unacceptable toxicity - refer to Section 7.2.1 for timing of the enoblituzumab dose on Day 22 if steroid pre-meds are needed due to an infusion reaction with the 1st enoblituzumab dose as there is a 14 day ban on corticosteroid use after the last dose of FT538

To determine the maximum tolerated dose (MTD) of FT538 monotherapy when administered via intraperitoneal (IP) catheter and in combination with intravenous (IV) enoblituzumab in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer.

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

MT2021-27 Intraperitoneal FT538 With Intravenous Enoblituzumab in Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Tumors will be biopsied to assess tumor microenvironment.

The primary objective of the study is to determine the maximum tolerated dose (MTD) of FT538 monotherapy when administered via intraperitoneal (IP) catheter and in combination with intravenous (IV) enoblituzumab in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer.

Monitor the patient for signs of acute infusion related reaction during and after IP infusion. For IV infusion signs of a possible reaction are rigors and chills, rash, urticaria, hypotension, dyspnea, and angioedema.

Overall response rate is defined as number of patients who have a partial or complete response to therapy divided by the total number of patients who received treatment.

Number of participants experiencing progression free survival at one year follow up

Number of participants experiencing adverse events with the combination of Enoblituzumab and FT538

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.

Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.

Emmanuel Antonarakis, MD

This study evaluates the safety, anti-tumor effect, and immunogenicity of Enoblituzumab given before radical prostatectomy. All patients will receive Enoblituzumab for 6 weekly doses beginning 50 days prior to radical prostatectomy.

This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity of neoadjuvant MGA271 given prior to radical prostatectomy in men with intermediate and high-risk localized prostate cancer. Eligible patients will receive MGA271 at a dose of 15mg/kg IV given weekly for 6 doses beginning 50 days prior to radical prostatectomy. 14 days after the last dose of MGA271, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and 90 days after surgery. Patients will then be followed by their urologists according to standard institutional practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.

In Amendment 1, the study was expanded to enroll an additional 16 patients for a total of 32 patients to continue evaluating safety and better estimate the clinical benefit of Enoblituzumab in terms of undetectable PSA level (\<0.1 ng/mL) at 12 months following radical prostatectomy.

Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer

Mean staining percentage of AR in harvested prostate tissue, assessed by immunohistochemistry (IHC) staining for AR protein.

Concentration (picogram/3 mg) of testosterone and 5α-dihydrotestosterone (DHT) in prostate tissue.

Number of participants with changes in cellular composition, upregulation and downregulation of immune checkpoints, and other markers of activity versus exhaustion.

CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by immunohistochemistry (IHC) in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage of each of these in tumor tissue

Fraction of peripherally expanded clones that are tumor associated for each participant.

Number of participants with CD16A, CD32A, and CD32B on Fc receptor.

Number of participants with upregulation and downregulation of immune checkpoints and other markers of activity versus exhaustion, as assessed by flow cytometry at treatment day 1 (pre-treatment), treatment day 36 (post-treatment), and 30 days post-prostatectomy.

Number of participants with B7-H3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment).

PD-1, LAG3, and TIM3 expression in prostate tumor specimens will be assessed by IHC (immunohistochemistry) in the primary core specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed as the mean staining percentage in tumor tissue.

Number of participants with antigen-spread to on-target and off-target antigens.

Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0

Number of participants with undetectable Prostate Specific Antigen (PSA \<0.1 ng/mL) at 12 months following radical prostatectomy

Quantify markers of apoptosis in prostate tumor specimens of treated patients using TUNEL staining and expressed as the mean staining percentage in tumor tissue

Quantify markers of cell proliferation in prostate tumor specimens of treated patients using Ki-67 staining and expressed by the mean staining percentage in tumor tissue

Mean staining percentage of CD8+ T-cells in harvested prostate glands from treated patients

Mean staining percentage of PD-L1 in tumor tissue, assessed by immunohistochemistry (IHC) in the primary core specimens (pre-treatment) and the prostatectomy surgical specimens (post-treatment).

Mean staining percentage of Treg cells in tumor tissue of treated patients, assessed through immunohistochemistry.

Mean staining percentage of CD4+ T-cells in tumor tissue of treated patients, assessed through immunohistochemistry.

Mean staining percentage of NK cells in harvested prostate glands.

Number of participants with positive or negative MGA271 detection in post-treatment prostate tumor specimens, as evaluated by IHC of fresh frozen sections.

Number of participants who achieve pCR, defined as absence of tumor identification on standard histological analysis of resected prostate specimens.

Number of participants with undetectable PSA (\<0.1 ng/mL) at 3 months after prostatectomy.

Median time (months) from prostatectomy to time when PSA is ≥ 0.2 ng/mL. Estimated using Kaplan-Meier method.

Number of participants with change in Gleason grade group from pre-treatment biopsy vs. post-treatment biopsy. "Downgrade" refers to a net grade group change less than zero, "upgrade" refers to net grade group change more than zero, and "no change" refers to stable Gleason grade group. Gleason grade groups are defined as grade group 1 (Gleason score ≤ 6), grade group 2 (Gleason score 3+4=7), grade group 3 (Gleason score 4+3=7), grade group 4 (Gleason score 8), and grade group 5 (Gleason scores 9-10).The lower the grade group, the better the outcome.

The PSA percentage change is calculated as the difference from the PSA at day 50 prior to prostatectomy and PSA at screening. A negative value of PSA percentage change ("PSA percentage \< 0") indicates a decrease in PSA from screening, and a positive value (PSA percentage change \>= 0) indicates an increase in PSA from screening.

MacroGenics

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Age, Continuous

Smoking History

Family History of Prostate Cancer

The Eastern Cooperative Oncology Group (ECOG) scale measures performance status, with scores ranging from 0-5; 0= fully active, performs without restriction, 1= can ambulate, but restricted in physically strenuous activity, 2= ambulatory and capable of self-care, but unable to work, active for \>50% of waking hours, 3= limited self-care, confined to bed or chair for \>50% of waking hours, 4= completely disabled, totally confined to bed/chair, 5= deceased

Eastern Cooperative Oncology Group (ECOG) performance status

Normal (BMI 18.5 - 24.9)

Overweight (BMI 25.0 - 29.9)

Obese (BMI ≥ 30.0)

Body-mass index (kg/m^2)

Grade Group 3: 4+3

Grade Group 4: 4+4

Grade Group 5: 4+5, 5+4, or 5+5

Gleason grade groups are defined as grade group 1 (Gleason score ≤ 6), grade group 2 (Gleason score 3+4=7), grade group 3 (Gleason score 4+3=7), grade group 4 (Gleason score 8), and grade group 5 (Gleason scores 9-10). A higher grade group reflects a worse outcome.

Gleason Group / Gleason sum at biopsy

Number of subjects who received therapy for prostate cancer prior to enrollment.

Previous Therapy

Stage T3 is defined as cancer growth outside of the prostate and possibly spread to the seminal vesicles.

Stage T3 at initial diagnosis

Participants who met eligibility criteria

Dr. Emmanuel Antonarakis

Grade 1

Grade 2

Grade 3

Grade 4

Number of Participants With Treatment-related Adverse Events

PSA < 0.1 ng/mL

PSA ≥ 0.1 ng/mL

Efficacy of Neoadjuvant Enoblituzumab as Assessed by PSA0 Response Rate

Quantify Markers of Apoptosis in Prostate Tumor Specimens of Treated Patients

Only 30 of the 32 participants enrolled in the trial had evaluable tissue samples.

Mean Staining Percentage of Markers of Cell Proliferation

CD8+ T Cell Infiltration

PD-L1 Expression

Regulatory T Cell (Treg) Infiltration

CD4+ T Cell Infiltration

Natural Killer (NK) Cell Density

Positive

Negative

The Overall Number of Participants Analyzed represents those evaluable for this outcome. Of the 32 participants who received study treatment, data from 2 subjects was not evaluable.

Enoblituzumab (MGA271) Drug Distribution Evaluated by Detection of MGA271 in Tumor Tissue

Pathological Complete Responses (pCR)

PSA <0.1 ng/mL

PSA ≥0.1 ng/mL

PSA Response Rates

Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.

Enoblituzumab: Enoblituzumab 15mg/kg IV (in the vein) weekly for 6 doses beginning 50 days prior to radical prostatectomy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FT516 and IL2 With Enoblituzumab for Ovarian Cancer	NCT04630769	Ovarian Cancer Fallopian Tube ... Primary Periton...	IP FT516 Enoblituzumab IL-2	18 Years -	Masonic Cancer Center, University of Minnesota
FT516 and IL2 With Enoblituzumab for Ovarian Cancer	NCT04630769	Ovarian Cancer Fallopian Tube ... Primary Periton...	IP FT516 Enoblituzumab IL-2	18 Years -	Masonic Cancer Center, University of Minnesota
MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer	NCT05708924	Cancer Solid Tumor Ovarian Cancer Peritoneal Canc... Fallopian Tube ...	FT538 Enoblituzumab	18 Years -	Masonic Cancer Center, University of Minnesota
Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer	NCT02923180	Prostate Cancer	Enoblituzumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate and High-Risk Prostate Cancer	NCT02923180	Prostate Cancer	Enoblituzumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer	NCT04634825	Head and Neck C... Head and Neck N... Head and Neck S...	Enoblituzumab Retifanlimab Tebotelimab	18 Years -	MacroGenics
Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer	NCT02475213	Melanoma Head and Neck C... Non Small Cell ... Urethelial Carc...	Enoblituzumab Pembrolizumab MGA012	18 Years -	MacroGenics
Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer	NCT04634825	Head and Neck C... Head and Neck N... Head and Neck S...	Enoblituzumab Retifanlimab Tebotelimab	18 Years -	MacroGenics
Enoblituzumab Plus MGA012 or MGD013 in Squamous Cell Carcinoma of the Head and Neck	NCT04129320	Head and Neck C... Squamous Cell C...	enoblituzumab MGA012 MGD013	18 Years -	MacroGenics

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