TROP2-CAR-NK / UT MD Anderson Cancer Center - LARVOL DELTA

Phase 1 dose escalation and expansion study of TROP2 CAR-engineered IL-15-transduced cord blood-derived NK cells in combination with cetuximab in patients with colorectal cancer (CRC) with minimal residual disease (MRD). (ASCO-GI 2026) - P1 | "Funded by ASCO CDA Clinical Trial Registration Number: NCT06358430 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • Minimal residual disease • P1 data • Residual disease • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL15

"Genome-wide CRISPR screens in primary human NK cells identify novel regulators enhancing CAR-NK Cell antitumor efficacy" (DGHO 2025) - "Furthermore, transcriptional profiling of patient-derived NK cells from 17 diverse cancer types reinforced the clinical relevance of these findings, revealing elevated expression of identified regulators in tumor-infiltrating NK cells compared to healthy donor controls.Notable pathways highlighted include components of the Cul5-RING ubiquitin ligase, Mediator and SAGA complexes, chromatin remodeling factors, and NFκB regulators—pinpointing transcriptional and post-translational modifications as essential for NK cell fitness and resilience under sustained tumor pressure.Specifically, disruption of MED12, ARIH2, and CCNC dramatically improved antitumor activity in both non-transduced and CAR-engineered NK cells equipped with IL-15-armored CARs targeting CD70 and TROP2. Mechanistically, ARIH2- and CCNC-deficient TROP2-CAR-NK cells exhibited increased metabolic fitness and expansion of cytotoxic subsets, as revealed by mass cytometry.Multiplex-edited ARIH2/CCNC-deficient..."

Clinical • IO biomarker • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • CD70 • IL15

Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jul 2028 ➔ Jan 2028 | Trial primary completion date: Jul 2026 ➔ Oct 2027

Platinum resistant • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA1 • BRCA2 • TACSTD2

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) - P1 | N=42 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Minimal residual disease • Colorectal Cancer • Oncology • Solid Tumor

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) - P1 | N=42 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Jan 2027 ➔ Jan 2029

Combination therapy • Minimal residual disease • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ovarian cancer, mesonephric-like adenocarcinoma, and pancreatic cancer. (ASCO 2024) - P1/2 | "Subjects enrolled will be admitted to the hospital, receive lymphodepleting chemotherapy (fludarabine 30 mg/m 2 and cyclophosphamide 300mg/m 2 ) on days -5 to -3, and will receive a single dose of cryopreserved and thawed intraperitoneal TROP2-CAR/IL15-transduced CB-NK cells on day 0. Severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5. The first patient on this trial was treated in January 2024."

IO biomarker • P1/2 data • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • IL15 • TACSTD2

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) - P1 | N=42 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

Combination therapy • Minimal residual disease • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients With Advanced Solid Tumors (TROPIKANA) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Apr 2028 ➔ Apr 2038

Metastases • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • BRAF • EGFR • HER-2 • NTRK • PD-L1 • ROS1 • TACSTD2

Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA1 • BRCA2 • TACSTD2

Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients With Advanced Solid Tumors (TROPIKANA) (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2024 ➔ Oct 2023

Enrollment open • Metastases • Trial initiation date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • BRAF • EGFR • HER-2 • NTRK • PD-L1 • ROS1 • TACSTD2

Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients With Advanced Solid Tumors (TROPIKANA) (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

Metastases • New P1 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ALK • BRAF • EGFR • HER-2 • NTRK • PD-L1 • ROS1 • TACSTD2

Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=51 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1/2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA1 • BRCA2 • TACSTD2