RECRUITING

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)

Conditions

Colorectal Cancer Minimal Residual Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.

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)

Quick Facts

Study Start:2024-12-02

Study Completion:2029-01-18

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06358430

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants must be 18 years or older. 2. Participants must be willing and able to provide informed consent. 3. 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. 4. 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. 5. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3). 6. Life expectancy \> 3 months. 7. 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. 8. Female participants who become pregnant or suspect pregnancy must immediately notify their doctor. Females' participants who become pregnant will be taken off study. 9. 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. 10. 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. 11. Participants must have adequate organ function as defined below (Table 1) within 10 days prior to the start of lymphodepleting chemotherapy: 12. 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. 13. Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen \>92% in room air. 14. Willing to undergo mandatory blood collections and biopsies as required by the study. 15. 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.	1. Participants with known active disease by RECIST v1.1. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. Prior genetically modified T or NK cell therapy. 8. Has diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent). 9. 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. 10. 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. 11. History of interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD. 12. Active infection requiring systemic therapy. 13. Known human immunodeficiency virus (HIV) infection. 14. Known active or chronic hepatitis B or hepatitis C virus infection. 15. Known history of active tuberculosis (Mycobacterium Tuberculosis). 16. 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. 17. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study. 18. Has had an allogenic tissue/solid organ transplant. 19. 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. 20. Prolongation of corrected QT interval using Fridericia's formula to \>480 milliseconds, unless cleared after cardiology evaluation. 21. 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.

Inclusion Criteria

Exclusion Criteria

1. Participants must be 18 years or older.
2. Participants must be willing and able to provide informed consent.
3. 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.
4. 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.
5. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
6. Life expectancy \> 3 months.
7. 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.
8. Female participants who become pregnant or suspect pregnancy must immediately notify their doctor. Females' participants who become pregnant will be taken off study.
9. 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.
10. 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.
11. Participants must have adequate organ function as defined below (Table 1) within 10 days prior to the start of lymphodepleting chemotherapy:
12. 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.
13. Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen \>92% in room air.
14. Willing to undergo mandatory blood collections and biopsies as required by the study.
15. 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.

1. Participants with known active disease by RECIST v1.1.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Prior genetically modified T or NK cell therapy.
8. Has diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent).
9. 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.
10. 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.
11. History of interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
12. Active infection requiring systemic therapy.
13. Known human immunodeficiency virus (HIV) infection.
14. Known active or chronic hepatitis B or hepatitis C virus infection.
15. Known history of active tuberculosis (Mycobacterium Tuberculosis).
16. 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.
17. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
18. Has had an allogenic tissue/solid organ transplant.
19. 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.
20. Prolongation of corrected QT interval using Fridericia's formula to \>480 milliseconds, unless cleared after cardiology evaluation.
21. 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.

Contacts and Locations

Study Contact

Maria Pia Morelli, MD, PhD

CONTACT

(713) 745-1297

mpmorelli@mdanderson.org

Principal Investigator

Maria Pia Morelli, MD, PhD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Maria Pia Morelli, MD, PhD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-02

Study Completion Date2029-01-18

Study Record Updates

Study Start Date2024-12-02

Study Completion Date2029-01-18

Terms related to this study

Additional Relevant MeSH Terms

Colorectal Cancer
Minimal Residual Disease