CAR-NK Cells + Belzutifan for Pancreatic Cancer

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combining CAR-engineered NK cells (a type of immunotherapy) with a medication called belzutifan for pancreatic cancer. The researchers aim to determine the safety of this combination and identify the best dose for future studies. This trial targets individuals with pancreatic cancer unresponsive to previous treatments like FOLFIRINOX or gemcitabine, who are willing to undergo certain procedures and tests. Participants will receive part of the treatment in the hospital and continue taking belzutifan at home. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be at least 5 half-lives from your last cytotoxic chemotherapy before starting the trial, and you cannot be on certain treatments like live vaccines or investigational agents close to the trial start.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TROP2 CAR-engineered NK cells could help treat cancers like pancreatic and ovarian. Early studies found these cells effective and safe, as they can kill cancer cells without causing major problems.

Belzutifan, another part of the trial, has been used in patients with Von Hippel-Lindau (VHL) disease and demonstrated a good safety record over long-term use. Some patients needed dose adjustments, but the treatment remained manageable. Its approval for other conditions further indicates its safety.

In summary, both treatments in this trial have demonstrated safety in previous studies. The TROP2 CAR-NK cells and belzutifan have been well-tolerated, with manageable side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of CAR-NK cells and Belzutifan for pancreatic cancer because it introduces a novel approach to treatment. Unlike traditional therapies like chemotherapy or targeted drugs, this treatment uses engineered immune cells, specifically TROP2 CAR/IL-15 TGFBR2 KO NK cells, to target and destroy cancer cells more effectively. Additionally, Belzutifan is an oral medication that can be self-administered at home, potentially making it more convenient for patients compared to standard intravenous treatments. This combination has the potential to enhance the body's natural immune response against cancer while offering a more patient-friendly treatment regimen.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that TROP2 CAR-engineered NK cells, which participants in this trial will receive, could effectively fight cancers like pancreatic cancer. These cells are specially designed to find and destroy cancer cells by recognizing a protein called TROP2 on their surface. Early studies suggest they can help shrink tumors in pancreatic and ovarian cancers.

Participants in this trial will also receive Belzutifan, which has shown promising results in treating pancreatic growths related to von Hippel–Lindau disease. Specifically, 84% of patients experienced tumor shrinkage or disappearance.

Together, these treatments in this trial offer hope for managing hard-to-treat pancreatic cancers.46789

Who Is on the Research Team?

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Maria Morelli, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pancreatic cancer that's advanced and can't be removed by surgery. They should have tried certain chemotherapies without success, be in good physical shape (ECOG 0 or 1), and not planning to get pregnant. Participants must agree to use contraception, have a port placed in their belly for treatment delivery, and consent to long-term follow-up.

Inclusion Criteria

I am 18 years old or older.
My cancer got worse after treatment with FOLFIRINOX or gemcitabine.
My cancer can be measured by scans.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TROP2 CAR/IL-15 TGFBR2 KO NK cells intraperitoneally and intravenously in combination with oral belzutifan

12 weeks
Inpatient for initial treatment, outpatient follow-up

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

12 weeks
Regular follow-up visits

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

  • TROP2 CAREngineered Cord Blood-Derived NK Cells

Trial Overview

The study tests TROP2 CAR/IL-15 TGFBR2 KO NK cells given into the abdomen combined with an oral drug called belzutifan for recurrent or spreading pancreatic cancer. It aims to find a safe dose and see how well patients tolerate this new therapy.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK cells + Oral BelzutifanExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Citations

Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion ...

Belzutifan was shown to have durable antitumor activity and a manageable safety profile in VHL disease–associated pNETs and non-pNET lesions such as serous ...

Real-world outcomes and toxicity with belzutifan in the ...

Conclusions: Our real-world outcomes demonstrate that belzutifan is effective in treatment of VHL disease and generally being well-tolerated.

Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion ...

Median follow-up was 37.8 months (range, 36.1–46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs.

Belzutifan Maintains High, Durable Responses in VHL ...

Belzutifan maintained a 70% ORR in VHL-associated RCC, with a 76.2% estimated 48-month DOR, highlighting its long-term efficacy. · The trial ...

European medicines agency review of belzutifan (Welireg) for ...

For VHL-RCC the overall response rate (ORR) was 67.2%, with a median duration of response not reached.

Real-world outcomes and safety in patients with VHL ...

Our real-world outcomes analysis of patients with VHL-associated tumors who are treated with Belzutifan shows an improved objective response.

Long-term Safety and Efficacy of Belzutifan in Von Hippel ...

Treatment interruption happened in 80% of the patients. The dose reduction was needed in 15 (60%) patients, with a median time of 6.8 months, ...

P17.34.B BELZUTIFAN IN CLINICAL PRACTICE: OUTCOMES ...

Among patients with RCC (n=26), overall response rate (ORR) was 19% and median time to best response (MTBR) was 7.4 months. Five patients had ...

Belzutifan for von Hippel–Lindau Disease: Pancreatic Lesion ...

Belzutifan was shown to have durable antitumor activity and a manageable safety profile in VHL disease–associated pNETs and non-pNET lesions such as serous ...