Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01CA260902 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
Not provided
Not provided
Not provided
This is a Phase I open-label clinical trial to assess the safety, feasibility, and preliminary efficacy of intrapleural administration of MOv19-BBz CAR T cells in patients with FRa+ cancers. This study will be initiated in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) only. Subjects will receive a single dose of MOv19-BBz CAR T cells via intrapleural infusion following lymphodepleting chemotherapy. Subjects without an existing intra-pleural catheter will have a temporary pleural catheter placed for the study. Subjects may initiate treatment with commercial checkpoint inhibitors per routine care beginning at least 28 days after receiving MOv19-BBz CAR T cells.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Level 1 (DL1) | Experimental | single dose of 5x10(7) MOv19-BBz CAR T cells administered via intrapleural infusion following lymphodepleting chemotherapy |
|
| Dose Level -1 (DL-1) | Experimental | 2.5x10(7) MOv19-BBz CAR T cells adminstered via intrapleural infusion, following lymphodepleting chemotherapy. This dose level will only be explored if ≥ 2 TLTs occur at any time in DL1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MOv19-BBz CAR T cells | Biological | Autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with FRa specificity. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events as assessed by CTCAE V5.0 | Type, frequency, severity, and attribution of adverse events. | Up to 15 years post-MOv19-BBz CAR T cell administration |
| Occurrence of treatment-limiting toxicities (TLTs) | Unacceptable toxicity as defined by the protocol. | 28 days post-MOv19-BBz CAR T cell administration |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate study feasibility | The proportion of enrolled subjects who are confirmed eligible and who receive study treatment as planned. | 6 months |
| Objective Response Rate (ORR) | Proportion of subjects with confirmed CR or PR per RECIST 1.1 criteria. |
Not provided
Inclusion Criteria:
Signed informed consent form
Documentation of tumor FRa expression by IHC at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available.
Disease-specific criteria:
a. NSCLC Patients: i. Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion.
ii. Failure of at least one prior line of standard of care therapy for advanced stage disease.
Patients must have evidence of active disease as defined by RECIST 1.1 criteria
Patients with asymptomatic CNS metastases that have been treated (and are off steroids for the treatment of CNS disease) are allowed. They must meet the following criteria
Adequate organ function defined as:
Male or female age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.
Exclusion Criteria:
Any clinically significant pleural effusion that cannot be drained with standard approaches.
Patients with significant lung disease as follows:
Active hepatitis B or hepatitis C infection
Any other active, uncontrolled infection
Class III/IV cardiovascular disability according to the New York Heart Association Classification
Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. [Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible].
Dependence on systemic steroids or immunosuppressant medications.
Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials Service | Contact | 215-349-8245 | PMCancerResearch@pennmedicine.upenn.edu |
| Name | Affiliation | Role |
|---|---|---|
| Andrew Haas, MD, PhD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008175 | Lung Neoplasms |
| D000077192 | Adenocarcinoma of Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C095424 | CF regimen |
Not provided
Not provided
Not provided
Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1.
Not provided
Not provided
Not provided
Not provided
| Cyclophosphamide/Fludarabine | Drug | Cytotoxic chemotherapy agents used for lymphodepletion prior to MOv19-BBz CAR T cell administration. |
|
| FRa Expression Testing | Device | Laboratory Developed Test used to determine subject eligibility |
|
| Up to 12 months following treatment with MOv19-BBz CAR T cells |
| Duration of Response (DOR) | Time from the date when confirmed CR or PR is first met, to the date of confirmed progressive disease, death due to any cause, or receipt of alternative anticancer therapy (excluding commercial immune checkpoint inhibitors as described by the study protocol); or it will be censored at the date of the last adequate assessment (whichever occurs first). | Up to 15 years following treatment with MOv19-BBz CAR T cells |
| Progression Free Survival (PFS) | Duration from study treatment to disease progression, receipt of alternative anti-cancer therapy, or death. | Up to 15 years following treatment with MOv19-BBz CAR T cells |
| Overall Survival (OS) | Duration of time from study treatment to the date of death, for any reason. | Up to 15 years following treatment with MOv19-BBz CAR T cell |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |