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)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This early study tests TCR1188-ABC cells in adults with certain cancers that have spread and have a KRAS G12V gene change. It will test different doses, check safety, see whether the cells can be made, and look for early signs that they work.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older and sign a form agreeing to join the study.
- Have cancer that has spread: pancreatic adenocarcinoma, bile duct cancer, colorectal cancer, or non-small cell lung cancer. A tissue test must confirm the cancer.
- Have lab tests showing the KRAS G12V gene change and HLA-A*11:01, an immune system marker.
- For pancreatic, bile duct, or lung cancer: have had at least one standard treatment for advanced cancer. Pancreatic cancer treatment must have included gemcitabine or fluorouracil (5-FU).
- For colorectal cancer: have had at least three standard treatments for advanced cancer, including required drug types unless you could not receive them. Cancer with the MSI-H marker also requires prior immune checkpoint treatment, unless you could not receive it.
- Have cancer visible on a scan within 8 weeks before eligibility is confirmed.
- Meet kidney, liver, heart, lung, and blood count requirements within 4 weeks before eligibility is confirmed. You must not need dialysis or blood transfusions to meet these requirements.
- Be fully active or able to walk and do light work, even if hard physical activity is limited.
Who can't join
- Have active hepatitis B or C, another uncontrolled infection, or a severely weakened immune system. People with HIV must have a CD4 immune cell count above 350, be on HIV treatment, and have a viral load below 400.
- Have severe heart-related limits on activity, unstable chest pain, a serious uncontrolled heartbeat problem, a heart attack in the past 6 months, or any past heart muscle inflammation.
- Have another severe, active health problem that the study doctor believes makes joining unsafe, or lung inflammation that needs steroid treatment.
- Have had another active cancer that grows into nearby tissue within the past 2 years. Some non-invasive cancers treated to cure them may be allowed.
- Be pregnant or breastfeeding. People who can have children must agree to use acceptable birth control.
- Need ongoing steroids that affect the whole body or drugs that weaken the immune system. Low-dose replacement steroids, steroid creams, and inhaled steroids may be allowed.
- Have an active disease in which the immune system attacks the body that needs immune-suppressing treatment equal to at least 10 mg of prednisone daily. These diseases affecting the brain or nerves, such as multiple sclerosis, also exclude you.
- Have active or untreated cancer in the brain, or an allergy to human serum albumin, DMSO, Dextran 40, or tocilizumab. Previously treated brain cancer spread may be allowed.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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 (see Appendix 5). 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, as described in protocol Section 4.3. 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, please see Section 5.6. 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 myocardial 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. Patients with active/untreated brain metastases. \[Note: History of treated metastases may still be eligible.\] 14. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.
Study sites (1)
PA
- University of Pennsylvania · Philadelphia, PA 19104Abramson Cancer Center Clinical Trials Service · Study contact · 215-349-8245 · PMCancerResearch@pennmedicine.upenn.eduMore trials in Philadelphia