MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT03585764 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: 830111 (UPCC-03818)1R01CA260902
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I study to establish safety and feasibility of intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (3)

• Number of Study Subjects With Treatment-related Adverse Events Using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  For this study, collection of adverse events will begin at the time of apheresis and will continue until the subject is off-study.

  Up to 34 months

• Manufacturing Feasibility

  Manufacturing feasibility is determined based on the "manufacturing failures" products. The number of manufactured products that do not meet release criteria for vector transduction efficiency, CART+ cell number, T cell purity, viability, and sterility will be determined and defined as "manufacturing failures".

  8 weeks

• Clinical Feasibility

  Clinical feasibility is defined as the proportion of subjects enrolled on this protocol who do not receive MOv19-BBz CAR T cells. Reasons for this occurrence include rapid clinical deterioration or death, and subject withdrawal.

  8 weeks

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Up to 33 months

• Overall Response Rates (ORR)

  Up to 33 months

• Overall Survival (OS)

  Up to 33 months

Study Arms (4)

Cohort 1: MOv19-BBz CAR T cells without chemo

EXPERIMENTAL

Cohort 1: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy.

Drug: MOv19-BBz CAR T cells; Device: Alpha Folate Receptor expression test

Cohort 2: MOv19-BBz CAR T cells after chemo

EXPERIMENTAL

Cohort 2: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

Drug: MOv19-BBz CAR T cells; Device: Alpha Folate Receptor expression test

Cohort 3: MOv19-BBz CAR T cells after chemo

EXPERIMENTAL

Cohort 3: (n=3 to 6 subjects): Single infusion of 1-3x108 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

Drug: MOv19-BBz CAR T cells; Device: Alpha Folate Receptor expression test

Cohort-1: without chemo;only if dose de-escalation required

EXPERIMENTAL

Cohort -1: (n= 3 to 6 subjects): Single Infusion of 1-3x106 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy. Up to 6 subjects will be infused in Cohort -1 with ≤ 1 DLT/6 subjects to establish the MTD.

Drug: MOv19-BBz CAR T cells; Device: Alpha Folate Receptor expression test

Interventions

MOv19-BBz CAR T cells DRUG

intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.

Cohort 1: MOv19-BBz CAR T cells without chemo; Cohort 2: MOv19-BBz CAR T cells after chemo; Cohort 3: MOv19-BBz CAR T cells after chemo; Cohort-1: without chemo;only if dose de-escalation required

Alpha Folate Receptor expression test DEVICE

Patients will first be pre-screened for alpha folate receptor expression. The test for alpha folate receptor expression is a laboratory developed test+, developed and conducted by the Hospital of the University of Pennsylvania Pathology and Laboratory Medicine lab to determine subject eligibility. This test is not an approved FDA device and its use is investigational.

Cohort 1: MOv19-BBz CAR T cells without chemo; Cohort 2: MOv19-BBz CAR T cells after chemo; Cohort 3: MOv19-BBz CAR T cells after chemo; Cohort-1: without chemo;only if dose de-escalation required

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed persistent or recurrent stage II to IV high grade serous epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Disease can be platinum-sensitive or platinum-resistant.
• Failure of at least two prior chemotherapy regimens for advanced stage disease. Prior therapies against PD-1 or PDL-1 are permissible.
• Confirmation of tumor aFR expression (≥70% of tumor cells with ≥2+ aFR staining).
• Subjects must have measureable disease as defined by RECIST 1.1 criteria.
• Patients with asymptomatic CNS metastases that have been treated and are off steroids are allowed. They must meet the following at the time of eligibility confirmation by physician-investigator:
• No concurrent treatment for the CNS disease
• No progression of CNS metastasis on brain MRI at screening
• No evidence of leptomeningeal disease or cord compression
• Patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Satisfactory organ and bone marrow function as defined by the following:
• i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 9 g/dL iv. Total bilirubin ≤ 2.0x the institutional normal upper limit unless secondary to bile duct obstruction by tumor v. Creatinine ≤ 1.5x the institutional normal upper limit vi. Albumin ≥2 vii. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5x the institutional normal upper limit viii. Cardiac ejection fraction of ≥40%
• Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤ 1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is therapeutically anti-coagulated for history of cancer-related thrombosis and has stable coagulation parameters.
• Provides written informed consent.
• Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

You may not qualify if:

• High grade serous ovarian, fallopian, or primary peritoneal cancer that is platinum refractory, defined as disease that has clinical or radiographic progression on platinum-based chemotherapy, as per the discretion of the treating physician.
• Patients with symptomatic CNS metastases are excluded.
• Participation in a therapeutic investigational study within 4 weeks prior to eligibility confirmation by physician-investigator, or anticipated treatment with another investigational product while on study. This refers to non-commercially approved investigational drugs different than those used in this protocol.
• Active invasive cancer other than ovarian cancers. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer) are not excluded.
• HIV infection
• Hepatitis B or hepatitis C infection
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to \>/= 10 mg of prednisone. Patients with autoimmune neurologic diseases (such as multiple sclerosis) will be excluded.
• Patients with active and uncontrolled infection.
• Patients requiring supplemental oxygen therapy.
• Prior therapy with lentiviral gene modified cells.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Any ascites requiring therapeutic drainage within 4 weeks prior to eligibility confirmation by physician-investigator.
• Pregnant or breastfeeding women.
• Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the physician-investigator, would make the patient inappropriate for entry into the study.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Cancer Institute (NCI): collaborator
• OvaCure Fundation: collaborator
• Alliance for Cancer Gene Therapy: collaborator
• Ovarian Cancer Alliance of Greater Cincinnati: collaborator

Study Sites (1)

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Payal D Shah, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 13, 2018
• Study Start: October 24, 2018
• Primary Completion: March 26, 2024
• Study Completion: March 26, 2024
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)