Personalized TCR-T: Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T)

NCT05349890 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 2021000572
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/Ib study of adoptively transferred T-cell receptor gene-engineered T cells (TCR-T) targeting tumor-specific antigens, with in vivo CD40 activation and PD-1 blockade, for patients with incurable cancers. The study design is a safety lead-in TCR-T with CD40/PD-1 (3+3), followed by Simon's Two-Stage expansion design, 80% power and 5% one-sided alpha: stage-one futility assessment at n = 10; stage-two assessment at n = 22, (accrual up to 24 to allow for potential study drop-out).

Conditions

Malignant Epithelial Neoplasms

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Incidence of adverse events

  2 years

• Severity of adverse events

  Severity of adverse events using CTCAE version 5.0

  2 years

Secondary Outcomes (4)

• Objective response rate

  2 years

• Duration of response

  2 years

• Clinical benefit rate

  2 years

• Overall survival

  2 years

Study Arms (1)

CDX-1140 + TCR-T + Pembro

EXPERIMENTAL

Patients will receive CDX-1440, TCR-T, and pembrolizumab.

Biological: TCR-transduced T cells; Drug: CDX-1140; Drug: Pembrolizumab

Interventions

TCR-transduced T cells BIOLOGICAL

TSA-reactive TCR-engineered T cells

CDX-1140 + TCR-T + Pembro

CDX-1140 DRUG

Recombinant fully human IgG2κ monoclonal antibody

CDX-1140 + TCR-T + Pembro

Pembrolizumab DRUG

Humanized immunoglobulin G4 (IgG4) monoclonal antibody

CDX-1140 + TCR-T + Pembro

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years and older with metastatic or locoregionally advanced epithelial cancers, that are considered incurable.
• Confirmation by Tran Laboratory of neoantigen-reactive TCR(s) suitable for TCR-gene therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
• Laboratory values:
• WBC ≥ 2000/uL
• Neutrophils ≥ 1000/uL
• Hgb \> 8.0 g/dl (patients may be transfused to reach this level)
• Platelets \> 100,000 cells/mm3
• Creatinine ≤ 2.0 mg/dL
• AST \& ALT ≤ 2.5 × ULN
• Alkaline phosphatase ≤ 2.5 × ULN
• Total bilirubin ≤ 2 × ULN (except patients with Gilbert's syndrome, who must have a total bilirubin ≤ 3.0 mg/dL). If total bilirubin is \>1.5, conjugated bilirubin must be ≤ ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then conjugated bilirubin must be \< 40% of total bilirubin.
• Patients positive for hepatitis B core antibody (anti-HBc, total), are eligible only if HBV DNA is non- detectable by qPCR.
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if HCV RNA is non-detectable by qPCR.
• Patients known positive for HIV 1/2 antibodies, are eligible if ARV treatment compliant with documented stable absolute CD4 count \> 300 cells/mm3 for at least 6 months and undetectable viral load.

You may not qualify if:

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receipt of any investigational anticancer therapy during the last 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment. Receipt of any prior anti-CD40 therapy.
• Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment, within 21 days (6 weeks for nitrosoureas) or at least 5 half-lives (whichever is longer) prior to the first dose of study treatment. Concurrent use of 4. hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• \. Local treatment of isolated lesions for palliative intent is acceptable (e.g., local surgery or radiotherapy), excluding target lesions, Palliative radiation therapy cannot be administered less than 1 week prior to the first dose of study treatment.
• \. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Participants must have recovered (to a grade 1 or lower) from all radiation-related toxicities, not require corticosteroids for this purpose and not have had radiation pneumonitis.
• \. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• \. History of organ transplant, including allogeneic stem cell transplantation. 9. History of (non-infectious) pneumonitis/interstitial lung disease or current pneumonitis/interstitial lung disease, including grade 1 pneumonitis (asymptomatic; clinical or diagnostic observation only; intervention not indicated).
• \. Uncontrolled intercurrent illness as deemed by the investigator, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• \. History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥1 year before the first dose of investigational product and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease (per investigator discretion).
• Adequately treated carcinoma in situ without evidence of disease (per investigator discretion) 12. History of leptomeningeal carcinomatosis 13. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients whose brain metastases have been treated may participate provided they show radiographic stability (imaging at least four weeks apart showing no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent and anti-seizure medications for at least 14 days prior to the start of treatment. Patients on a stable dose of seizure medicines for epilepsy unrelated to cancer are eligible for the trial.
• \. History of active primary immunodeficiency. 15. Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
• \. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent).:
• Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.

Sponsors & Collaborators

• Providence Health & Services: lead
• Celldex Therapeutics: collaborator
• Providence Cancer Center, Earle A. Chiles Research Institute: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Carcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Rom Leidner, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

• Eric Tran, PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: April 27, 2022
• Study Start: April 3, 2023
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): April 15, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)