Zolbetuximab + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 6 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Strong CYP3A, UGT1A1 inhibitors

Disqualifiers: HIV, Hepatitis B, Autoimmune, others

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

Compensation: Varies

Number of Visits: 21

Duration: Up to 16 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with pancreatic cancer that has spread. It combines a drug called zolbetuximab with chemotherapy, specifically a regimen known as mFOLFIRINOX. Zolbetuximab aids the immune system in attacking cancer cells by attaching to a specific protein on the tumor. The trial aims to determine the safety of this combination and assess participants' ability to handle any side effects. People with metastatic pancreatic cancer who haven't received chemotherapy before are suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using strong inhibitors or inducers of CYP3A or UGT1A1 with irinotecan, you may need to adjust your medication. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that zolbetuximab combined with chemotherapy is likely to be safe for humans?

A previous study found that combining zolbetuximab with chemotherapy was safe for people with pancreatic cancer. Researchers focused on patients whose cancer had spread to other parts of the body, checking for serious side effects and determining the highest tolerable dose. The results showed that patients tolerated the treatment well, with manageable side effects.

Zolbetuximab targets a protein called Claudin 18.2, often found in these cancers, helping the immune system attack the cancer cells. This approach has shown promise in other studies, offering hope for its use in treating pancreatic cancer as well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pancreatic cancer?

Unlike the standard chemotherapy treatments for pancreatic cancer, such as gemcitabine or nab-paclitaxel, the investigational drug Zolbetuximab offers a unique approach by targeting a specific protein called claudin 18.2, which is often present on pancreatic cancer cells. This specificity could potentially make Zolbetuximab more effective at attacking cancer cells while sparing healthy ones, reducing side effects compared to traditional chemotherapy. Researchers are particularly excited about combining Zolbetuximab with mFOLFIRINOX, a regimen already known for its efficacy, which could enhance treatment outcomes and provide a more powerful option against this challenging cancer.

What evidence suggests that zolbetuximab with chemotherapy could be an effective treatment for pancreatic cancer?

Studies have shown that zolbetuximab targets a protein called Claudin 18.2, often found in pancreatic cancer cells. This protein enables zolbetuximab to activate the immune system to attack the tumor. Research indicates that combining zolbetuximab with chemotherapy may improve outcomes for patients with pancreatic cancer. In this trial, participants will receive zolbetuximab with mFOLFIRINOX. One study found that a treatment combination called S-IROX, which includes zolbetuximab, controlled the disease in 73.7% of patients, compared to 62.2% with traditional chemotherapy. This suggests that zolbetuximab could enhance the effectiveness of standard treatments for pancreatic cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults over 18 with metastatic pancreatic cancer who haven't had chemotherapy can join this study. They must have a specific protein on their tumor cells and not be pregnant or breastfeeding. Participants need measurable cancer lesions, cannot have progressed after certain chemotherapies, and women must agree to contraception for six months post-treatment.

Inclusion Criteria

My cancer is a type of pancreatic cancer confirmed by lab tests.

Participant must meet all laboratory criteria

Participant agrees not to participate in another interventional study while receiving study intervention

Exclusion Criteria

Participant has positive test for HIV, active hepatitis B, or hepatitis C infection

I have received certain treatments within specific timeframes.

Participant has history of investigational study intervention administration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zolbetuximab in combination with chemotherapy (mFOLFIRINOX) every 14 days in a 28-day cycle

Up to 16 months

Infusions every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including health checks and blood tests

Several visits post-treatment

Visits 7 days after treatment ends and several more based on health status

What Are the Treatments Tested in This Trial?

Interventions

• mFOLFIRINOX
• Zolbetuximab

Trial Overview The trial is testing zolbetuximab combined with mFOLFIRINOX chemotherapy in patients with pancreatic cancer. Zolbetuximab targets a protein on the tumor to activate the immune system against it. The treatment is given through an infusion every two weeks in a cycle of 28 days.

How Is the Trial Designed?

Group I: zolbetuximab and mFOLFIRINOX Experimental Treatment 2 Interventions

Participants will receive 1 of 2 dose levels of zolbetuximab in combination with mFOLFIRINOX.

mFOLFIRINOX is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as mFOLFIRINOX for:

• Pancreatic ductal adenocarcinoma (PDAC)

Approved in United States as mFOLFIRINOX for:

• Advanced pancreatic cancer

Approved in Canada as mFOLFIRINOX for:

• Resectable pancreatic ductal adenocarcinoma

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Published Research Related to This Trial

Adjuvant FOLFOX-A is a feasible treatment option for patients with resected pancreatic ductal adenocarcinoma, with a median overall survival of 53.5 months based on a phase II trial involving 25 patients.

While FOLFOX-A showed promising survival outcomes, it also resulted in notable side effects, including fatigue (58%) and neutropenia (26%), indicating a need for careful monitoring of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant FOLFOX+Nab-Paclitaxel (FOLFOX-A) for Pancreatic Cancer: A Brown University Oncology Research Group Phase II Study (BrUOG295). Raufi, AG., Breakstone, R., Leonard, K., et al.[2021]

In a study of 76 patients with metastatic pancreatic cancer, mFOLFIRINOX treatment resulted in significantly better objective response rates (20.0% vs 0%) and progression-free survival (3.7 months vs 2.1 months) compared to the oral fluoropyrimidine S-1.

While mFOLFIRINOX showed promising treatment outcomes, it also led to more frequent severe side effects, such as grade 3-4 neutropenia and peripheral sensory neuropathy, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with S-1 as second-line chemotherapy in metastatic pancreatic cancer. Ikezawa, K., Kiyota, R., Takada, R., et al.[2022]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

In a phase I trial involving 50 patients with advanced pancreatic cancer, the combination of nivolumab, nab-paclitaxel, and gemcitabine showed a manageable safety profile, with 48 patients experiencing grade 3/4 treatment-emergent adverse events, but only one dose-limiting toxicity reported.

The treatment resulted in a median overall survival of 9.9 months and an overall response rate of 18%, indicating limited efficacy, which led to the conclusion that further investigation of this combination is not supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Wainberg, ZA., Hochster, HS., Kim, EJ., et al.[2022]

In a study of 59 patients with advanced pancreatic cancer, those who experienced moderate to severe peripheral neuropathy (PN) from first-line modified FOLFIRINOX (mFFX) showed similar overall survival (OS) and time-to-treatment failure (TTF) compared to those with mild or no PN when treated with second-line Gemcitabine plus nab-paclitaxel (GnP).

The presence of mFFX-induced PN did not significantly affect the efficacy or safety of GnP, suggesting that GnP remains a viable treatment option for patients regardless of their PN status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of First-Line FOLFIRINOX-Induced Peripheral Neuropathy on the Efficacy of Second-Line GnP in Patients with Unresectable Advanced Pancreatic Cancer. Sadaka, S., Iwashita, T., Fujii, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345990/

Advances in the Management of Pancreatic Cancer Retrospective data have echoed these findings, suggesting improved R0 resection rates and survival outcomes with neoadjuvant chemoradiation.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03816163

NCT03816163 | A Study of Zolbetuximab (IMAB362) in ... Zolbetuximab is being studied as a treatment for people with pancreatic cancer. Most people with pancreatic cancer have a protein called Claudin 18.2 ...

3. cureus.com cureus.com/articles/375577-novel-therapies-in-advanced-pancreatic-cancer-a-peak-beyond-the-realms-of-gene-targeting

Novel Therapies in Advanced Pancreatic Cancer: A Peak ... The study aims to evaluate the safety and effectiveness of GN alone or in combination with zolbetuximab in approximately 369 patients diagnosed ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0304383524007572

Emerging targets in gastric and pancreatic cancer Claudin 18.2 is a selective target in gastric and pancreatic cancer therapy. Zolbetuximab shows promise by improving survival in gastric cancer.

5. withpower.com withpower.com/trial/phase-1-claudin-182-cldn182-positive-metastatic-pancreatic-adenocarcinoma-4-2024-8401f

Zolbetuximab + Chemotherapy for Pancreatic Cancer In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988091/

Immune-Based Strategies for Pancreatic Cancer in the ... Primary outcomes evaluated will be safety, dose-limiting toxicity, maximum tolerated dose, and recommended dose for the phase I component ...

7. mskcc.org mskcc.org/cancer-care/clinical-trials/24-382

A Phase 1 Study of Zolbetuximab Plus Chemotherapy in ... ... zolbetuximab with chemotherapy is safe in people with pancreatic cancer. The people in this study have pancreatic cancer that has metastasized (spread). In ...