Phase 1/2 Study TROP2 CAREngineered Cord Blood-Derived NK Cells + Belzutifan In Pancreatic Cancer

NCT07377526 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-1462NCI-2026-00667
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II study evaluating the intraperitoneal delivery of TROP2 CAR/IL-15 TGFBR2 KO NK cells in combination with oral belzutifan (120 mg daily) for patients with recurrent, locally advanced, unresectable and metastatic pancreatic cancer. The primary objectives are to assess safety and determine the recommended Phase II dose (RP2D).

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  Through study completion; an average of 1 year

Study Arms (1)

Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK cells + Oral Belzutifan

EXPERIMENTAL

Treatment will be administered on an inpatient basis for lymphodepleting therapy, cell infusion and first doses of belzultifan, and on an outpatient basis after patients are dismissed from the hospital and continue self-administering belzultifan at home.

Drug: TGFBR2 KO CAR27/IL-15 NK cells

Interventions

TGFBR2 KO CAR27/IL-15 NK cells DRUG

Given by mouth

Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK cells + Oral Belzutifan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 18 years or older.
• Subjects must be willing and able to provide informed consent.
• Subjects with a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma or ampullary-type carcinoma
• Subjects who have progressive disease after receiving initial treatment with either FOLFIRINOX, or a gemcitabine-based therapy
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• A female participant is eligible to participate if at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
• A WOCBP who agrees to follow the contraceptive guidelines in Appendix 1 during the treatment period and for at least 3 months after the last dose of study treatment.
• Subjects must have measurable disease present as defined by modified RECIST v1.1
• Subjects must be at least 5 half-lives from the last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy.
• Subjects must be willing to undergo intraperitoneal port placement and scheduled peritoneal fluid and peripheral blood draws.
• Agree to sign the consent to the long-term follow-up protocol PA17-0843 to fulfill the institutional responsibilities to various regulatory agencies
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

You may not qualify if:

• Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 3 months after the last dose of trial treatment.
• If a WOCBP has a positive urine pregnancy test within 72 hours prior to the start of treatment that cannot be confirmed as negative, a serum pregnancy test will be required (see Appendix 1).
• 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 PI. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of the start of the study intervention.
• Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to any non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Is currently receiving another investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• 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 participants 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.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• 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 that required steroids or has current pneumonitis/interstitial lung disease.
• Active infection requiring systemic therapy.
• Known history of uncontrolled Human Immunodeficiency Virus (HIV) infection. Patients with HIV infection and an undetectable viral load may participate.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Maria Morelli, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Morelli, MD,PHD

CONTACT

(713) 745-1297; mpmorelli@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: January 30, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (1)