CholangiocarcinomaPhase 1NCT07594067
TCR1188-ABC Cells in KRAS-mutated Cancers
A Phase 1 study testing TCR1188-ABC cells, Fludarabine + Cyclophosphamide combination and Tocilizumab in people with Cholangiocarcinoma and Colorectal Cancer, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma, Colorectal Cancer, Non-Small Cell Lung Cancer
- What is being tested?
- TCR1188-ABC cells, Fludarabine + Cyclophosphamide combination and Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2026to Nov 2042
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
- 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)
- Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO/MUGA
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
- 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:
- Hemoglobin ≥ 8 g/dL
- Absolute neutrophil count ≥ 1000/μL
- Platelet count ≥ 100,000/μL
- ECOG Performance Status that is either 0 or 1.
- Signed, written informed consent
Who cannot join
- Active hepatitis B or hepatitis C infection
- 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.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5).
- 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].
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- Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.
- 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, please see Section 5.6.
- 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 myocardial infarction within 6 months of physician-investigator confirmation of eligibility.
- Prior history of myocarditis.
- Patients with pneumonitis/interstitial lung disease requiring steroid treatment.
- Patients with active/untreated brain metastases. [Note: History of treated metastases may still be eligible.]
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Abramson Cancer Center Clinical Trials Service contact
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Abramson Cancer Center Clinical Trials Service, 215-349-8245, PMCancerResearch@pennmedicine.upenn.edu
About this study
Official title: 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.
- Conditions
- Cholangiocarcinoma, Colorectal Cancer, Non-Small Cell Lung Cancer, Pancreatic Adenocarcinoma
- Being tested
- TCR1188-ABC cells, Fludarabine + Cyclophosphamide combination, Tocilizumab
- Medical subject headings
- Cholangiocarcinoma, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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)
TocilizumabDrug
Single administration of 8mg/kg on Day 2 (+3d)
| Study group | Role | What they receive |
|---|---|---|
| Dose level -1 | Experimental | 1.11 x 10^8 TCR1188-ABC cells Receives: Biological: TCR1188-ABC cells; Drug: Fludarabine + Cyclophosphamide combination; Drug: Tocilizumab |
| Dose level 1 | Experimental | 3.33 x 10^8 TCR1188-ABC cells Receives: Biological: TCR1188-ABC cells; Drug: Fludarabine + Cyclophosphamide combination; Drug: Tocilizumab |
| Dose level 2 | Experimental | 1 x 10^9 TCR1188-ABC cells Receives: Biological: TCR1188-ABC cells; Drug: Fludarabine + Cyclophosphamide combination; Drug: Tocilizumab |
| Dose level 3 | Experimental | 3 x 10^9 TCR1188-ABC cells Receives: Biological: TCR1188-ABC cells; Drug: Fludarabine + Cyclophosphamide combination; Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 28 days post-TCR1188-ABC cell infusion
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 15 years after last TCR1188-ABC cells administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2026
- Study startDec 2026 (estimated)
- Primary completionNov 2042 (estimated)
- Study completionNov 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07594067
- Sponsor's protocol ID
- 27225
- Other IDs
- 1UG3CA283652-01
- Status last verified
- Oct 2026
- First submitted
- 11 May 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No