Colorectal CancerPhase 1NCT06358430
Dose Escalation and Expansion Study of TROP2 CAR Engineered IL-15- Transduced Cord Blood-derived NK Cells in Combination With Cetuximab in Patient With Colorectal Cancer (CRC) With Minimal Residual Disease (MRD)
A Phase 1 study testing Fludarabine Phosphate, Cyclophosphamide and Cetuximab in people with Colorectal Cancer and Minimal Residual Disease, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Minimal Residual Disease
- What is being tested?
- Fludarabine Phosphate, Cyclophosphamide and Cetuximab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2024to 18 Jan 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Participants must be 18 years or older.
- Participants must be willing and able to provide informed consent.
- Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
- In both the dose escalation and dose expansion cohorts, participants must have documented colorectal cancer (CRC) with MRD following complete disease resection followed by standard-of-care adjuvant treatment. MRD is defined as NO evidence of radiological disease (including patients with undefinable lesion with max diameter <1 cm or with a short axis < 1cm for lymph nodes) and presence of circulating ctDNA in the bloodstream.
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
- Life expectancy > 3 months.
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- A female patient is eligible to participate if at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR
- A WOCBP who agrees to follow the contraceptive guidelines in Appendix 4 during the study treatment period and for 6 months post TROP2-CAR-NK cell infusion.
- Female participants who become pregnant or suspect pregnancy must immediately notify their doctor. Females' participants who become pregnant will be taken off study.
- Male participants must agree to follow the contraceptive guidelines in Appendix 4 during the study treatment period and for 6 months post TROP2-CAR-NK cell infusion. Male participants who father a child or suspect that they have fathered a child must immediately notify their doctor.
- WOCBP must have a negative urine pregnancy test within 72 hours prior to the start of lymphodepleting chemotherapy. If a WOCBP has a urine pregnancy test that cannot be confirmed as negative, a serum (beta-human chorionic gonadotropin [â-hCG]) pregnancy test will be required.
- Participants must have adequate organ function as defined below (Table 1) within 10 days prior to the start of lymphodepleting chemotherapy:
- Table 1. Adequate Organ Function Laboratory Values Systemic Function Test Laboratory Value Hematologic ANC = ≥1500/ƒÊL Platelets = ≥100,000/ƒÊL Hemoglobin = ≥9.0 g/dLa Renal CrCl by Cockcroft-Gault formula = ≥45 mL/min for patients with creatinine >1.5 x ULNb Hepatic Total bilirubin = ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels >1.5 x ULN AST and ALT = ≤2.5 x ULN (≤5 x ULN for patients with history of resected liver metastases) Coagulation PT/INR aPT = ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range
- Left ventricular ejection fraction >50%. Of note, those patients with risk factors and/or with LVEF <55% additional testing may need to be performed as per institutional guidelines and/or PI guidance.
- Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen >92% in room air.
- Willing to undergo mandatory blood collections and biopsies as required by the study.
- Willing to stay within a 2-hour drive (approximately 100-mile radius) of the study site during the first 4 weeks after the TROP2-NK cell infusion.
Who cannot join
- Participants with known active disease by RECIST v1.1.
- Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post TROP2-CAR-NK cell infusion.
- Has received systemic anticancer therapy within 2 weeks or 3 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy. For patients treated with monoclonal antibodies, at least 3 weeks must have elapsed prior to the start of lymphodepleting chemotherapy. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.
- Participants must have recovered from all AEs due to previous therapies to . Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI). If a participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the start of lymphodepleting chemotherapy.
- Has received prior radiotherapy within 2 weeks of the start of lymphodepleting chemotherapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis or colitis.
- Has received a live vaccine within 6 weeks prior to TROP2-CAR-NK infusion and for at least 24 months post infusion. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette. Guerin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMistR) are live attenuated vaccines and are not allowed.
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- Prior genetically modified T or NK cell therapy.
- Has diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent).
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to patients who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
- History of interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
- Active infection requiring systemic therapy.
- Known human immunodeficiency virus (HIV) infection.
- Known active or chronic hepatitis B or hepatitis C virus infection.
- Known history of active tuberculosis (Mycobacterium Tuberculosis).
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participants to participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Has had an allogenic tissue/solid organ transplant.
- Clinically significant cardiovascular disease within 12 months prior to the start of lymphodepleting chemotherapy, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebrovascular event, or cardiac arrhythmia associated with hemodynamic instability. NOTE: medically controlled arrhythmia would be permitted if meet criteria per Appendix X.
- Prolongation of corrected QT interval using Fridericia's formula to >480 milliseconds, unless cleared after cardiology evaluation.
- Participant with bleeding or thrombotic disorders or at risk for severe hemorrhage. Participants with known deep vein thrombosis/pulmonary embolism who are on appropriate anti-coagulation treatment are eligible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL-15- Transduced Cord Blood-derived NK Cells in Combination With Cetuximab in Patient With Colorectal Cancer (CRC) With Minimal Residual Disease (MRD)
To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.
Read the detailed description
Primary Objective:
- To determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of TROP2-CAR-NK cells combined with cetuximab in patients with MRD CRC.
- To evaluate circulating tumor DNA (ctDNA) clearance (undetectable) at 3 months
Secondary Objectives:
- Determine progression-free survival.
- To quantify the persistence of infused allogeneic donor TROP2-CAR-NK cells in the peripheral blood of the recipient.
- To evaluate blood- and tissue-based biomarkers at baseline associated with response and resistance to TROP2-CAR-NK cell infusion in combination with cetuximab.
Exploratory Objectives:
- To profile and assess dynamic immune changes in the tumor microenvironment.
- Quantify the average circulating ctDNA change from TROP2-CAR-NK infusion to progression or initiation of a new cancer therapy and association with PFS.
- To evaluate patient-reported quality of life (QoL).
- Conditions
- Colorectal Cancer, Minimal Residual Disease
- Being tested
- Fludarabine Phosphate, Cyclophosphamide, Cetuximab, TROP2-CAR-NK Cells, Rimiducid (AP1903)
- Medical subject headings
- Colorectal Neoplasms, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Fludarabine, Fludara®
Given by IV
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
Given by IV
CetuximabDrug
Also called C225, Erbitux™, IMC-C225, MOAB C225
Given by IV
TROP2-CAR-NK CellsDrug
Given by IV
Rimiducid (AP1903)Drug
Given by IV
Lymphodepleting ChemotherapyProcedure or surgery
Given by Chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation + Dose Expansion | Experimental | Up to 5 dose levels of TROP2-CAR-NK cells will be tested in the Dose Escalation phase. Up to 12 participants maximum will be enrolled at any dose level, in groups of 3 participants at a time. The first group of participants will receive the lowest dose level.
Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the recommended dose of TROP2-CAR-NK cells is found. When that dose level is confirmed, the final group of 12 participants will be enrolled at that dose level. Receives: Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: Cetuximab; Drug: TROP2-CAR-NK Cells; Drug: Rimiducid (AP1903); Procedure: Lymphodepleting Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start2 Dec 2024
- Primary completion18 Jan 2029 (estimated)
- Study completion18 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bellicum Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Maria Pia Morelli, MD, PhD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06358430
- Sponsor's protocol ID
- 2023-1017
- Other IDs
- NCI-2024-03107
- Status last verified
- Jul 2026
- First submitted
- 5 Apr 2024
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL-15- Transduced Cord Blood-derived NK Cells in Combination With Cetuximab in Patient With Colorectal Cancer (CRC) With Minimal Residual Disease (MRD)
- ClinicalTrials.gov ID
- NCT06358430
- Acronym / sponsor ID
- 2023-1017
- Conditions
- Colorectal Cancer, Minimal Residual Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bellicum Pharmaceuticals
- Study start
- 2 Dec 2024 (actual)
- Primary completion
- 18 Jan 2029 (estimated)
- Study completion
- 18 Jan 2029 (estimated)
- First posted
- 10 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.
Detailed description
Primary Objective:
- To determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of TROP2-CAR-NK cells combined with cetuximab in patients with MRD CRC.
- To evaluate circulating tumor DNA (ctDNA) clearance (undetectable) at 3 months
Secondary Objectives:
- Determine progression-free survival.
- To quantify the persistence of infused allogeneic donor TROP2-CAR-NK cells in the peripheral blood of the recipient.
- To evaluate blood- and tissue-based biomarkers at baseline associated with response and resistance to TROP2-CAR-NK cell infusion in combination with cetuximab.
Exploratory Objectives:
- To profile and assess dynamic immune changes in the tumor microenvironment.
- Quantify the average circulating ctDNA change from TROP2-CAR-NK infusion to progression or initiation of a new cancer therapy and association with PFS.
- To evaluate patient-reported quality of life (QoL).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation + Dose Expansion | Experimental | Drug: Fludarabine Phosphate, Drug: Cyclophosphamide, Drug: Cetuximab, Drug: TROP2-CAR-NK Cells, Drug: Rimiducid (AP1903), Procedure: Lymphodepleting ChemotherapyUp to 5 dose levels of TROP2-CAR-NK cells will be tested in the Dose Escalation phase. Up to 12 participants maximum will be enrolled at any dose level, in groups of 3 participants at a time. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the recommended dose of TROP2-CAR-NK cells is found. When that dose level is confirmed, the final group of 12 participants will be enrolled at that dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Participants must be 18 years or older.
- Participants must be willing and able to provide informed consent.
- Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
- In both the dose escalation and dose expansion cohorts, participants must have documented colorectal cancer (CRC) with MRD following complete disease resection followed by standard-of-care adjuvant treatment. MRD is defined as NO evidence of radiological disease (including patients with undefinable lesion with max diameter <1 cm or with a short axis < 1cm for lymph nodes) and presence of circulating ctDNA in the bloodstream.
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
Key exclusion criteria (21 listed)
- Participants with known active disease by RECIST v1.1.
- Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post TROP2-CAR-NK cell infusion.
- Has received systemic anticancer therapy within 2 weeks or 3 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy. For patients treated with monoclonal antibodies, at least 3 weeks must have elapsed prior to the start of lymphodepleting chemotherapy. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.
- Participants must have recovered from all AEs due to previous therapies to . Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI). If a participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the start of lymphodepleting chemotherapy.
- Has received prior radiotherapy within 2 weeks of the start of lymphodepleting chemotherapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis or colitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine PhosphateAlso: Fludarabine, Fludara®Given by IV | Drug | Dose Escalation + Dose Expansion |
| CyclophosphamideAlso: Cytoxan®, Neosar®Given by IV | Drug | Dose Escalation + Dose Expansion |
| CetuximabAlso: C225, Erbitux™, IMC-C225, MOAB C225Given by IV | Drug | Dose Escalation + Dose Expansion |
| TROP2-CAR-NK CellsGiven by IV | Drug | Dose Escalation + Dose Expansion |
| Rimiducid (AP1903)Given by IV | Drug | Dose Escalation + Dose Expansion |
| Lymphodepleting ChemotherapyGiven by Chemotherapy | Procedure or surgery | Dose Escalation + Dose Expansion |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Pia Morelli, MD, PhD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine Phosphate, Cyclophosphamide and Cetuximab in people with Colorectal Cancer and Minimal Residual Disease, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.