NCT07594067

Brief Summary

This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1188-ABC cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or non-small cell lung cancer (NSCLC) will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.

Trial Health

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Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
195mo left

Started Jul 2026

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 11, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 18, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

July 1, 2026

Expected
16 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2042

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2042

Last Updated

May 18, 2026

Status Verified

May 1, 2026

Enrollment Period

16 years

First QC Date

May 11, 2026

Last Update Submit

May 11, 2026

Conditions

Colorectal CancerNon-Small Cell Lung CancerCholangiocarcinomaPancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

  • Number of Subjects with treatment related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) V6.0

    Type, frequency, severity, and attribution of adverse events

    Up to 15 years following TCR1188-ABC cell administration

  • Occurrence of dose-limiting toxicities (DLTs)

    Type, frequency, severity, and attribution of dose limiting adverse events as defined by the protocol

    Up to 28 days following TCR1188-ABC cell administration

  • Identification of the maximum tolerated dose (MTD)

    The highest dose at which 0 or 1 DLT occurs in 6 DLT-evaluable subjects will be declared the MTD.

    28 days post-TCR1188-ABC cell infusion

Secondary Outcomes (6)

  • Occurrence of product release failures

    3 months

  • Proportion of TCR1188-ABC cells that fail to meet the protocol-defined dose

    3 months

  • Overall Response Rate (ORR)

    Up to 12 months following TCR1188-ABC cells administration

  • Duration of Response (DOR)

    Up to 15 years following TCR1188-ABC cell administration

  • Progression-Free Survival (PFS)

    Up to 15 years following TCR1188-ABC cell administration

  • +1 more secondary outcomes

Study Arms (4)

Dose level -1

EXPERIMENTAL

1.11 x 10\^8 TCR1188-ABC cells

Biological: TCR1188-ABC cellsDrug: Fludarabine + Cyclophosphamide combinationDrug: Tocilizumab

Dose level 1

EXPERIMENTAL

3.33 x 10\^8 TCR1188-ABC cells

Biological: TCR1188-ABC cellsDrug: Fludarabine + Cyclophosphamide combinationDrug: Tocilizumab

Dose level 2

EXPERIMENTAL

1 x 10\^9 TCR1188-ABC cells

Biological: TCR1188-ABC cellsDrug: Fludarabine + Cyclophosphamide combinationDrug: Tocilizumab

Dose level 3

EXPERIMENTAL

3 x 10\^9 TCR1188-ABC cells

Biological: TCR1188-ABC cellsDrug: Fludarabine + Cyclophosphamide combinationDrug: Tocilizumab

Interventions

TCR1188-ABC cellsBIOLOGICAL

TCR1188 modified, base-edited autologous CD4+ and CD8+ T cells expressing TCR1188 and a scFv fragment specific to ILT4 (LILRB2) as a Single infusion on Day 0

Dose level -1Dose level 1Dose level 2Dose level 3
Fludarabine + Cyclophosphamide combinationDRUG

Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5)

Dose level -1Dose level 1Dose level 2Dose level 3
TocilizumabDRUG

Single administration of 8mg/kg on Day 2 (+3d)

Dose level -1Dose level 1Dose level 2Dose level 3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients ≥ 18 years of age
  • Patients with one of the following diagnoses:
  • Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma
  • Histologically confirmed metastatic colorectal cancer
  • Histologically confirmed metastatic non-small cell lung cancer
  • HLA-A\*11:01 positive as confirmed by a CLIA certified laboratory.
  • KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.
  • Received prior treatment for their primary malignancy as follows:
  • Pancreatic Cancer/Cholangiocarcinoma Patients: At least one prior line of standard of care therapy for advanced stage disease. For pancreatic cancer patients, this must include a gemcitabine or fluorouracil (5 FU)-based regimen.
  • Colorectal Cancer Patients: At least three prior lines of standard of care therapy for advanced stage disease. Prior treatment must include all of the following unless the patient was ineligible for a specific therapy type: i). a fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimen, ii). an anti-vascular endothelial growth factor (VEGF) agent, and iii). regorafenib, trifluridine-tipiracil, or fruquintinib. Patients with microsatellite instability-high (MSI-H) disease must also have received, or be ineligible for, prior treatment with an immune checkpoint inhibitor.
  • Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.
  • Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.
  • Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:
  • Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
  • ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
  • +9 more criteria

You may not qualify if:

  • \. Active hepatitis B or hepatitis C infection 2. Patients with a severe acquired or inherited immunodeficiency, including HIV positive patients with a CD4 count ≤ 350 cells/μL. In order to qualify, HIV positive patients must also be on an established antiretroviral therapy regimen with a viral load of \<400 copies/mL.
  • \. Any other active, uncontrolled infection. 4. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  • \. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
  • \. Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
  • \. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.
  • \. Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications.
  • \. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
  • \. Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and/or mycocardial infarction within 6 months of physician-investigator confirmation of eligibility.
  • \. Prior history of myocarditis. 12. Patients with pneumonitis/interstitial lung disease requiring steroid treatment.
  • \. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

CholangiocarcinomaColorectal NeoplasmsCarcinoma, Non-Small-Cell Lung

Interventions

fludarabinetocilizumab

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract Diseases

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245PMCancerResearch@pennmedicine.upenn.edu

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

May 11, 2026

First Posted

May 18, 2026

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

July 1, 2042

Study Completion (Estimated)

July 1, 2042

Last Updated

May 18, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will not share

Locations

US(1)