A Study of Armed, Activated T-Cells in Patients With Advanced Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT04137536
• Recruitment Status: Active, not recruiting
• First Posted: October 24, 2019
• Last Update Posted: October 10, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: University of Virginia
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: October 21, 2019
• First Posted Date: October 24, 2019
• Last Update Posted Date: October 10, 2022
• Actual Study Start Date: October 17, 2019
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 22, 2019)

Evaluate toxicity [ Time Frame: 1 year ]

The NCI CTEP CTCAE v4.0 will be used.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Armed, Activated T-Cells in Patients With Advanced Pancreatic Cancer
• Official Title: Phase Ib Treatment of Advanced Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Bispecific Antibody Armed Activated T-Cells (BATs)
• Brief Summary: The purpose of this study is to find the safest dose and identify any bad side effects of EGFR-BATs (bispecific antibody-armed activated T cells) for people with advanced pancreatic cancer who have already received first-line standard chemotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Pancreatic Cancer
• Advanced Pancreatic Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms

Intervention

Drug: anti-EGFR-bispecific antibody armed activated T-cells

Phase I:

• First 3 participants, twice weekly infusions of 10^10 EGFR BATs infusions
• If there is toxicity in 0 or 1 of 3 participants, 3 additional participants will be added to the dose level of up to 10^10.
• If >/= 2 of 6 participants experience DLTs, then the dose will be reduced to 7.5 x 10^9 per infusion
• If only 0 or 1 participants has toxicity in the first 6, then the study will proceed to enroll in the expansion cohort

Expansion cohort:

- 8 infusions of 7.5 x 10^9 or 10^10 EGFR BATs in 22 evaluable participants (including the 6 participants treated at the maximum tolerated dose in Phase I)

Other Name: EGFR BATs

Study Arms

Experimental: Pancreatic Adenocarcinoma

Participants have metastatic pancreatic cancer who have received at least first line chemotherapy and have disease progression during or within 6 months of treatment.

Intervention: Drug: anti-EGFR-bispecific antibody armed activated T-cells

• Publications *: Park JA, Santich BH, Xu H, Lum LG, Cheung NV. Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release. J Immunother Cancer. 2021 May;9(5):e002222. doi: 10.1136/jitc-2020-002222.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 7, 2021): 7
• Original Estimated Enrollment (submitted: October 22, 2019): 25
• Estimated Study Completion Date: April 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histological or cytological proof of pancreatic adenocarcinoma. Must have metastatic pancreatic cancer who have received at least first line chemotherapy. Disease stability or progression during or within 6 months after treatment with 5-Fluorouracil (5-FU)- or gemcitabine-based chemotherapy. KPS>/= 70% or SWOG performance Status 0 or 1
• Evaluable disease by iRECIST criteria
• Absolute Neutrophil Count (ANC) >/= 1,000/mm^3
• Lymphocyte count >/= 400/mm^3
• Platelet Count >/= 75,000/mm^3
• Hemoglobin >/= 8 g/dL
• Serum Creatinine < 2.0 mg/dl, Creatinine Clearance >/=50 ml/mm (can be calculated or measured)
• Total Bilirubin </= 2 mg/dl (biliary stent is allowed)
• SGPT and SGOT <5.0 times normal
• LVEF >/= 55% at rest (<UGA or Echo)
• Age >/= 18 years at the time of consent (Written informed consent and HIPAA authorization for release of personal health information)
• Females of childbearing potential, and males, must be willing to use an effective method of contraception
• Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy

Exclusion Criteria:

• Any chemotherapy related toxicities from prior treatment, > grade 2 per CTCAE v4.0
• Known hypersensitivity to cetuximab or other EGFR antibody
• Treatment with any investigational agent within 14 days prior to being registered for protocol therapy
• Symptomatic brain metastasis
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Steroid premedication for imaging scans is allowed. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
• Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Known HIV infection
• Active bleeding or a pathological condition that is associated with a high risk of bleeding (therapeutic anticoagulation is allowed)
• Has an active infection requiring systemic therapy
• A serious uncontrolled medical disorder that in the opinion of the Investigator may be jeopardized by the treatment with protocol therapy.
• Females must not be breastfeeding
• Patient may be excluded if, in the opinion of the PI and investigator team, the patient is not capable of being compliant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04137536
• Other Study ID Numbers: 18-463
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: University of Virginia

Investigators

• Principal Investigator: Kenneth Yu, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: October 2022