TCR1188-ABC Cells in KRAS-mutated Cancers

Phase I, Open-Label Study of Autologous Mutant KRAS and ILT4-Redirected T-cell Receptor Cells (TCR1188-ABC)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Pancreatic Adenocarcinoma; Non-Small Cell Lung Cancer; Cholangiocarcinoma
• Intervention / Treatment: Biological: TCR1188-ABC cells; Drug: Fludarabine + Cyclophosphamide combination; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Abramson Cancer Center Clinical Trials Service; Phone Number: 215-349-8245; Email: PMCancerResearch@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Contact: Abramson Cancer Center Clinical Trials Service; Phone Number: 215-349-8245; Email: PMCancerResearch@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients ≥ 18 years of age

2. Patients with one of the following diagnoses:

   1. Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma
   2. Histologically confirmed metastatic colorectal cancer
   3. Histologically confirmed metastatic non-small cell lung cancer
3. HLA-A*11:01 positive as confirmed by a CLIA certified laboratory.
4. KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.

5. Received prior treatment for their primary malignancy as follows:

   1. 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.
   2. 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.
   3. Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.
6. Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.

7. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:

   1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
   2. ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
   3. Total bilirubin ≤ 1.5 mg/dL x ULN, unless the subject has Gilbert's syndrome (if so, direct bilirubin must be ≤ 2.0 mg/dL x ULN)
   4. Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO/MUGA
   5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air

8. Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:

   1. Hemoglobin ≥ 8 g/dL
   2. Absolute neutrophil count ≥ 1000/μL
   3. Platelet count ≥ 100,000/μL
9. ECOG Performance Status that is either 0 or 1.
10. Signed, written informed consent

Exclusion Criteria:

• 1. 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.

  3. Any other active, uncontrolled infection. 4. Class III/IV cardiovascular disability according to the New York Heart Association Classification.

  5. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.

  6. 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].

  7. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

  8. 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.

  9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

  10. Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and/or mycocardial infarction within 6 months of physician-investigator confirmation of eligibility.

  11. Prior history of myocarditis. 12. Patients with pneumonitis/interstitial lung disease requiring steroid treatment.

  13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level -1; 1.11 x 10^8 TCR1188-ABC cells	Biological: TCR1188-ABC cells; 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; Drug: Fludarabine + Cyclophosphamide combination; Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5); Drug: Tocilizumab; Single administration of 8mg/kg on Day 2 (+3d)
Experimental: Dose level 1; 3.33 x 10^8 TCR1188-ABC cells	Biological: TCR1188-ABC cells; 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; Drug: Fludarabine + Cyclophosphamide combination; Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5); Drug: Tocilizumab; Single administration of 8mg/kg on Day 2 (+3d)
Experimental: Dose level 2; 1 x 10^9 TCR1188-ABC cells	Biological: TCR1188-ABC cells; 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; Drug: Fludarabine + Cyclophosphamide combination; Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5); Drug: Tocilizumab; Single administration of 8mg/kg on Day 2 (+3d)
Experimental: Dose level 3; 3 x 10^9 TCR1188-ABC cells	Biological: TCR1188-ABC cells; 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; Drug: Fludarabine + Cyclophosphamide combination; Fludarabine: 30 mg/m2/day x 4 days (Day -7 to -4) Cyclophosphamide: 600mg/m2/day x 3 days (Day -7 to -5); Drug: Tocilizumab; Single administration of 8mg/kg on Day 2 (+3d)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of product release failures	Calculated based on the proportion of subjects with TCR1188-ABC cell products that fail to meet the product release criteria, out of the number of eligible subjects in whom manufacturing was attempted, will be calculated.	3 months
Proportion of TCR1188-ABC cells that fail to meet the protocol-defined dose	Proportion of subjects with TCR1188-ABC cell products that fail to meet the assigned dose, out of the number of eligible subjects in whom manufacturing was attempted.	3 months
Overall Response Rate (ORR)	Proportion of subjects with CR or PR as the best overall response as assessed by RECIST 1.1 from the first response assessment post-infusion until the end of the primary follow-up.	Up to 12 months following TCR1188-ABC cells administration
Duration of Response (DOR)	Duration of time from the date the response criteria of CR or PR is first met, to the date of confirmed disease progression, or the date of the last adequate disease assessment performed before the occurrence of another censoring event.	Up to 15 years following TCR1188-ABC cell administration
Progression-Free Survival (PFS)	Duration of time from the TCR1188-ABC cell infusion to the date of confirmed disease progression or death due to any cause, or the date of the last adequate disease assessment performed before the occurrence of another censoring event.	Up to 15 years following TCR1188-ABC cell administration
Overall Survival (OS)	Time from the first TCR1188-ABC cell infusion to death due to any cause; or censored at the date of last contact.	Up to 15 years after last TCR1188-ABC cells administration

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2042
• Study Completion (Estimated): July 1, 2042

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; tocilizumab; fludarabine
• Other Study ID Numbers: 27225; 1UG3CA283652-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No