Zolbetuximab + Chemotherapy for Pancreatic Cancer

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

12 Participants Needed

Trial Summary

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 the combination of Zolbetuximab and chemotherapy safe for humans?

The modified FOLFIRINOX (mFOLFIRINOX) chemotherapy regimen, which is part of the treatment being studied, has been associated with increased toxicity, including peripheral neuropathy (nerve damage causing tingling or numbness). This suggests that while it can be effective, it may also have significant side effects. ^{1 2 3 4 5}

What is the purpose of this trial?

Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. In this study, zolbetuximab will be given together with chemotherapy to people with pancreatic cancer. Zolbetuximab attaches to a protein called CLDN18.2 found at high levels on the surface of the cancer tumor. This switches on the immune system to attack the tumor. Adults 18 years or older with metastatic pancreatic cancer who have not previously had chemotherapy can take part in the study. There are 2 main aims of this study: * To check the safety of zolbetuximab, when given with chemotherapy in people with metastatic pancreatic cancer * To check if people could cope with (tolerate) any medical problems during the study This is an open-label study. This means people in the study and the study doctors will know that people will receive zolbetuximab with chemotherapy. Different small groups will receive lower to higher doses of zolbetuximab with chemotherapy. Zolbetuximab and chemotherapy will be given through a vein. This is called an infusion. People will receive zolbetuximab on the first day they receive chemotherapy. This will happen every 14 days in a 28-day cycle. People will receive zolbetuximab and chemotherapy in the study clinic and at home. Also, doctors will check for any medical problems. People will also have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. People will visit the study clinic about 7 days after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. After this, people will have several more visits to the study clinic for health checks. The number of visits and checks done at each visit will depend on the health of each person and whether they complete their treatment or not.

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

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

Participant must meet all laboratory criteria

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

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

Exclusion Criteria

I have severe fluid buildup in my chest or abdomen.

Participant has history of investigational study intervention administration

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

References

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Adjuvant FOLFOX+Nab-Paclitaxel (FOLFOX-A) for Pancreatic Cancer: A Brown University Oncology Research Group Phase II Study (BrUOG295). [2021]

3. Australia 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. [2022]

5. Switzerland 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. [2022]