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huCART-meso + VCN-01 in Pancreatic and Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05057715
Recruitment Status : Recruiting
First Posted : September 27, 2021
Last Update Posted : February 22, 2023
Sponsor:
Collaborator:
Theriva Biologics SL
Information provided by (Responsible Party):
University of Pennsylvania

Study Description
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Brief Summary:
This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCART-meso cells when given in combination with VCN-01 in a 3+3 dose (de)escalation design.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Serous Ovarian Cancer Biological: VCN-01 Biological: huCART-meso Cells Phase 1

Detailed Description:

This is a Phase I study evaluating the safety and feasibility of lentiviral transduced huCART-meso cells when given in combination with VCN-01 in a 3+3 dose (de)escalation design as follows:

  • Cohort 1 (N = 3-6): will receive VCN-01 as a single IV infusion of 3.3x1012 vp on Day 0, followed by a single dose of 5x107 huCART-meso cells on Day 14 via IV infusion. This cohort will be evaluated as follows:

    • If 1 DLT/3 subjects occurs, Cohort 1 will be expanded to enroll an additional 3 evaluable subjects.
    • If 0 DLT/3 subjects or 1 DLT/6 subjects, the study will advance to Cohort 2.

  • Cohort 2 (N = 3-6): will receive VCN-01 as a single IV infusion of 1x1013 vp on Day 0 followed by a single dose of 5x107 cells huCART-meso cells on Day 14 via IV infusion. This cohort will be evaluated as follows:

    • If 0 DLT/3 subjects or 1 DLT/3 subjects occurs, Cohort 2 will be expanded to enroll an additional 3 evaluable subjects. If 0 DLT/6 subjects or 1 DLT/6 subjects occurs, this dose combination will be defined as the recommended phase 2 dose (RP2D).
    • If 2 DLTs occur at any time, enrollment in this Cohort will be stopped. If less than 6 subjects were infused in Cohort 1 prior to Cohort 2 escalation, an additional 3 evaluable subjects will be infused at the Cohort 1 dose level to further demonstrate safety and to confirm Cohort 1 as the RP2D (with 0 DLT/6 subjects or 1 DLT/6 subjects).

In the event that 2 DLTs occur in Cohort 1, then enrollment in Cohort 1 will be stopped and Cohort -1 will be opened for evaluation. Cohort -1 will evaluate a different sequence of administration for these two investigational products at the same dose level used in Cohort 1.

• Cohort -1 (N = up to 6): will receive a single dose of 5x107 huCART-meso cells via IV infusions on Day 0 followed by VCN-01 as a single infusion of 3.3x1012 vp on Day 10. Up to 6 subjects will be infused in Cohort -1 unless > 1 DLTs are observed at any time.

The Day 0 infusions of the first two subjects in each cohort will be staggered by at least 42 days from the prior subject's 1st infusion (huCART-meso or VCN-01; depending on the cohort assignment), to allow for the assessment of DLTs and a formal decision regarding cohort progression, expansion, or de-escalation. Subsequent subject infusions within that cohort will be staggered by at least 14 days from the preceding subject's second infusion. Formal DLT assessments will be performed by the Clinical PI and Sponsor Medical Director in accordance with the definition provided in the protocol.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 3+3
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of Human Chimeric Antigen Receptor Modified T Cells (huCART-meso) Administered in Combination With VCN-01 in Patients With Pancreatic and Serous Epithelial Ovarian Cancer
Actual Study Start Date : February 17, 2022
Estimated Primary Completion Date : September 2038
Estimated Study Completion Date : September 2038

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Cohort 1
Single dose of 3.3x10(12) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.
 Biological: VCN-01
Intravenous administration of VCN-01

Biological: huCART-meso Cells
Intravenous administration of huCART-meso cells
Active Comparator: Cohort 2
Single dose of 1x10(13) vp of VCN-01 on Day 0, followed by a single dose of 5x10(7) of huCART-meso cells on Day 14.
 Biological: VCN-01
Intravenous administration of VCN-01

Biological: huCART-meso Cells
Intravenous administration of huCART-meso cells
Active Comparator: Cohort -1
In the event that 2 DLTs occur in Cohort 1, then enrollment in Cohort 1 will be stopped and Cohort -1 will be opened for evaluation. Enrolled subjects will receive a single dose of huCART-meso cells on Day 0 followed by a single dose of 3.3x10(12) vp of VCN-01 on Day 14.
 Biological: VCN-01
Intravenous administration of VCN-01

Biological: huCART-meso Cells
Intravenous administration of huCART-meso cells


Outcome Measures
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Primary Outcome Measures :
  1. Type, frequency, severity, and attribution of AEs/SAEs as assessed by CTCAE v 5.0 [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Proportion of subjects enrolled who receive one or both of the intended study infusions [ Time Frame: 2 years ]
  2. Overall Response Rate (ORR) [ Time Frame: 15 years ]
  3. Best Overall Response (BOR) [ Time Frame: 15 years ]
  4. Duration of Response (DOR) [ Time Frame: 15 years ]
  5. Progression Free Survival (PFS) [ Time Frame: 15 years ]
  6. Overall Survival (OS) [ Time Frame: 15 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with one of the following diagnoses:

    1. Histologically confirmed unresectable or metastatic pancreatic adenocarcinoma; OR
    2. Persistent or recurrent serous epithelial ovarian cancer
  2. Progression or intolerance to at least one prior standard of care chemotherapy for advanced stage disease.
  3. Subjects must have measurable disease as defined by RECIST 1.1 criteria.
  4. Patients ≥ 18 years of age.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  6. Adequate organ and bone marrow function defined as:

    1. Hemoglobin ≥ 9 g/dL
    2. Platelets ≥ 75,000/µl
    3. PT/INR and PTT ≤ 1.5 x ULN
    4. Bilirubin ≤ 2.0 x ULN
    5. Creatinine ≤ 1.5 x ULN
    6. ALT/AST ≤ 5 x ULN (subjects with liver metastases) or ALT/AST ≤ 2.5 x ULN (subjects without liver metastases)
    7. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
    8. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
  7. Provides written informed consent.
  8. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in the protocol

Exclusion Criteria:

  1. Patients with known CNS metastases
  2. Active invasive cancer other than the one of the two cancers targeted by this study. Patients with active non-invasive cancers (such as non-melanoma skin cancer, superficial cervical and bladder and prostate cancer with PSA level < 1.0) are not excluded.
  3. Active hepatitis B or hepatitis C infection.
  4. Chronic hepatitis C with a FibroScan score equivalent to fibrosis stage 2 (F2) or greater.
  5. Patients with known cirrhosis.
  6. Patients with ongoing or active infection.
  7. Patients with a known history of Li Fraumeni syndrome or retinoblastoma protein pathway germinal deficiency.
  8. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10 mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
  9. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (≤ 10mg equivalent of prednisone). Use of inhaled steroids is allowable.
  10. Patients requiring supplemental oxygen therapy.
  11. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
  12. Any clinically significant pericardial effusion, Class II-IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 4) or other cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study. This determination will be made by a cardiologist if cardiac issues are suspected.
  13. Pregnant or breastfeeding women.
  14. Treatment with a PD-1 or PD-L1 inhibitor, including but not limited to nivolumab, pembrolizumab, atezolizumab, and/or durvalumab, within 2 months prior to eligibility confirmation by a physician-investigator.

  15. Patients with significant lung disease as follows:

    1. Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.
    2. Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
    3. Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05057715


Contacts
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Contact: Abramson Cancer Center Clinical Trials Services 855-216-0098 PennCancerTrials@emergingmed.com
Contact: Janos L. Tanyi, MD, PhD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Abramson Cancer Center Clinical Trials Service    855-216-0098    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
University of Pennsylvania
Theriva Biologics SL
Investigators
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Principal Investigator: Janos L. Tanyi, MD, PhD University of Pennsylvania
More Information
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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT05057715    
Other Study ID Numbers: UPCC# 03821, IND #27590
First Posted: September 27, 2021    Key Record Dates
Last Update Posted: February 22, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Ovarian Diseases
 Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type