Trial Title:
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)
NCT ID:
NCT06358430
Condition:
Colorectal Cancer
Minimal Residual Disease
Conditions: Official terms:
Colorectal Neoplasms
Neoplasm, Residual
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Cetuximab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fludarabine Phosphate
Description:
Given by IV
Arm group label:
Dose Escalation + Dose Expansion
Other name:
Fludarabine
Other name:
Fludara®
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given by IV
Arm group label:
Dose Escalation + Dose Expansion
Other name:
Cytoxan®
Other name:
Neosar®
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
Given by IV
Arm group label:
Dose Escalation + Dose Expansion
Other name:
C225
Other name:
Erbitux™
Other name:
IMC-C225
Other name:
MOAB C225
Intervention type:
Drug
Intervention name:
TROP2-CAR-NK Cells
Description:
Given by IV
Arm group label:
Dose Escalation + Dose Expansion
Intervention type:
Drug
Intervention name:
Rimiducid (AP1903)
Description:
Given by IV
Arm group label:
Dose Escalation + Dose Expansion
Intervention type:
Procedure
Intervention name:
Lymphodepleting Chemotherapy
Description:
Given by Chemotherapy
Arm group label:
Dose Escalation + Dose Expansion
Summary:
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:
1. 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.
2. To evaluate circulating tumor DNA (ctDNA) clearance (undetectable) at 3 months
Secondary Objectives:
1. Determine progression-free survival.
2. To quantify the persistence of infused allogeneic donor TROP2-CAR-NK cells in the
peripheral blood of the recipient.
3. 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:
1. To profile and assess dynamic immune changes in the tumor microenvironment.
2. Quantify the average circulating ctDNA change from TROP2-CAR-NK infusion to
progression or initiation of a new cancer therapy and association with PFS.
3. To evaluate patient-reported quality of life (QoL).
Criteria for eligibility:
Criteria:
Inclusion 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:
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
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.
Exclusion Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Maria Pia Morelli, MD, PhD
Phone:
713-745-1297
Investigator:
Last name:
Maria Pia Morelli, MD, PhD
Email:
Principal Investigator
Start date:
October 31, 2024
Completion date:
January 18, 2029
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Bellicum Pharmaceuticals, Inc.
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06358430
http://www.mdanderson.org
