Zolbetuximab + Chemotherapy for Pancreatic Cancer

Not currently recruiting at 201 trial locations

Overseen By Astellas Pharma Global Development

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Other cancers, Heart disease, Infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with metastatic pancreatic cancer, specifically those whose tumors express the protein Claudin 18.2 (CLDN18.2). It tests a drug called zolbetuximab, which aims to help the immune system target and attack cancer cells, alongside standard chemotherapy. Participants will receive either zolbetuximab with chemotherapy or chemotherapy alone to determine which is more effective and safe. This trial suits adults whose cancer has spread and who have not yet received chemotherapy. Individuals with this specific protein marker in their tumors and who have not undergone chemotherapy may be a good fit. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you need to take medicines that suppress your immune system or if you have recently taken certain treatments like radiotherapy or investigational drugs. It's best to discuss your specific medications with the study doctor.

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

Research shows that zolbetuximab, combined with the chemotherapy drugs nab-paclitaxel and gemcitabine, is under study for its safety and effectiveness in treating pancreatic cancer. Studies have found that most patients generally tolerate this combination treatment well. However, like all cancer treatments, some side effects have been reported, including tiredness, nausea, and lower blood cell counts, which are common with chemotherapy.

The current study aims to determine the best dose of zolbetuximab to use with these chemotherapy drugs. As this is an early-stage study, the safety is still being fully assessed. The study is ongoing, and researchers are closely monitoring patient responses and any side effects. Prospective participants should discuss the potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for pancreatic cancer?

Researchers are excited about zolbetuximab for pancreatic cancer because it targets a specific protein, claudin 18.2, which is found on cancer cells. This mechanism is different from standard chemotherapy options like gemcitabine and nab-paclitaxel, which work by stopping cell division. By adding zolbetuximab to the mix, there's potential to more precisely attack cancer cells without harming normal cells, potentially leading to better outcomes with fewer side effects. This unique targeting approach could offer new hope for patients with pancreatic cancer, a condition known for limited treatment options.

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

Research shows that zolbetuximab might help treat pancreatic cancer by targeting a protein called Claudin 18.2, often found in these tumors. In animal studies, zolbetuximab slowed tumor growth, even when standard treatments like gemcitabine were no longer effective. In this trial, one group of participants will receive zolbetuximab combined with nab-paclitaxel and gemcitabine. Zolbetuximab is also approved for treating stomach cancer when this protein is present, highlighting its potential in targeting tumors. However, recent studies in pancreatic cancer have not achieved all their goals, so its effectiveness remains under investigation. Another group in this trial will receive nab-paclitaxel and gemcitabine without zolbetuximab. Combining zolbetuximab with chemotherapy aims to boost the body's immune response against cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic adenocarcinoma that tests positive for CLDN18.2 and haven't had chemotherapy before. They should have a life expectancy of at least 12 weeks, be able to follow contraceptive guidelines, and not be pregnant or breastfeeding. People who've had certain recent treatments or surgeries, active infections, other cancers needing treatment, severe allergies to study drugs' components, or specific heart conditions can't join.

Inclusion Criteria

Subject agrees not to participate in other interventional studies while receiving study drug in present study.

I have a tumor that can be measured and it's either outside the area treated with radiation or has grown after radiation.

Subject has predicted life expectancy ≥ 12 weeks.

Exclusion Criteria

I have severe fluid buildup in my chest or abdomen.

You can participate in the study if your hepatitis C blood test shows that you had the infection in the past, but the virus is not currently in your body.

I do not have active hepatitis B according to my test results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in Phase

Participants receive one of two different doses of zolbetuximab with chemotherapy to establish the recommended dose for the next phase.

4 weeks

Multiple visits for infusions and monitoring

Randomization Phase

Participants are randomized to receive either zolbetuximab with chemotherapy or chemotherapy alone. Treatment cycles are 4 weeks long.

Up to 65 months

Regular visits for infusions, health checks, and scans

Follow-up

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

Up to 65 months

Clinic visits post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Nab-paclitaxel
• Zolbetuximab

Trial Overview The trial is testing the effectiveness and safety of a drug called zolbetuximab combined with Nab-Paclitaxel and Gemcitabine as the first line of treatment. It aims to confirm the best dose for phase 2 trials, measure how long patients live while on this treatment, monitor side effects, check how their bodies process the drugs (pharmacokinetics), and assess any changes in their quality of life.

How Is the Trial Designed?

Group I: zolbetuximab +nab-paclitaxel + gemcitabine Experimental Treatment 3 Interventions

Participants will be treated with zolbetuximab in combination with nab-paclitaxel and gemcitabine for the phase 1 portion of the study to establish the recommended dose of zolbetuximab for the phase 2 portion. In the phase 2 portion, the participants will be treated with zolbetuximab at dose determined by the phase 1 portion of the study in combination with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.

Group II: nab-paclitaxel + gemcitabine Active Control 2 Interventions

Participants will be treated with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

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

In a study of 27 elderly Japanese patients (aged ≥ 75) with non-curatively resectable pancreatic cancer, the combination of nanoparticle albumin-bound paclitaxel (nab-PTX) and gemcitabine (GEM) showed a high disease control rate of 92.6%, indicating strong efficacy in managing the disease.

Despite its effectiveness, the treatment was associated with significant adverse effects, including a 51.9% incidence of grade 3 or higher hemotoxicity and a 22% rate of grade ≥ 3 peripheral nerve disorders, highlighting the need for careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. Hasegawa, R., Okuwaki, K., Kida, M., et al.[2022]

Nab-paclitaxel, when combined with gemcitabine, significantly improves overall survival in adults with metastatic pancreatic cancer, reducing the risk of death by 28% compared to gemcitabine alone, based on a multinational phase III study.

The treatment has a manageable safety profile, with most adverse events being grade 3 or lower, and common side effects like neutropenia and peripheral neuropathy are generally reversible with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albumin-bound paclitaxel: a review of its use for the first-line combination treatment of metastatic pancreatic cancer. Hoy, SM.[2021]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

In a retrospective study of 29 patients with advanced pancreatic carcinoma and elevated bilirubin levels, treatment with nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) was found to be safe, showing no unexpected toxicities.

The median overall survival for patients treated with nab-P/G was 11.7 months, with no significant differences in survival based on bilirubin levels, indicating that nab-P/G is a feasible treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. Pelzer, U., Wislocka, L., Jühling, A., et al.[2022]

The recent phase III MPACT trial demonstrated that nab-paclitaxel, when added to gemcitabine, significantly improved survival rates in patients with metastatic pancreatic cancer, indicating its efficacy in a previously challenging area.

The success of nab-paclitaxel highlights the importance of innovative drug delivery technologies, such as albumin nanoparticle formulations, in enhancing the effectiveness of anticancer therapies while minimizing toxicities associated with traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The winning formulation: the development of paclitaxel in pancreatic cancer. Ma, WW., Hidalgo, M.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a large Phase III clinical trial, the combination of nab-paclitaxel and gemcitabine significantly improved treatment outcomes for advanced pancreatic adenocarcinoma, increasing the response rate from 7% to 23%.

Patients receiving the combination therapy also experienced longer progression-free survival (5.5 months compared to 3.7 months) and overall survival (8.5 months compared to 6.7 months) compared to those treated with gemcitabine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer. Al-Hajeili, M., Azmi, AS., Choi, M.[2021]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a small study of 6 women with heavily pretreated HER2-negative metastatic breast cancer, the combination of nab-paclitaxel (nab-P) and bevacizumab (B), with or without gemcitabine (G), showed promising safety and preliminary efficacy, with only one patient experiencing significant toxicity.

Out of the 6 patients, 2 achieved partial responses and 4 had stable disease, indicating that this combination therapy may be effective, warranting further investigation in a formal phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. Lobo, C., Lopes, G., Silva, O., et al.[2022]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6287799/

Characterization of zolbetuximab in pancreatic cancer ... In mouse xenograft tumors derived from human PC cell lines, including gemcitabine-refractory ones, zolbetuximab slowed tumor growth, benefited ...

3. oncologypipeline.com oncologypipeline.com/apexonco/few-pancreatic-gleams-hope-vyloy

Few pancreatic Gleams of hope for Vyloy | ApexOnco Vyloy is FDA approved as part of a chemo combo for first-line gastric cancer, but only in patients with 75% or higher Claudin18.2 expression.

4. bioworld.com bioworld.com/articles/725067-astellas-zolbetuximab-misses-pancreatic-cancer-phase-ii-endpoint

Astellas' zolbetuximab misses pancreatic cancer phase II ... Astellas said the trial's outcome in pancreatic cancer is expected to have a minor impact on its financial results for the fiscal year ending ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03816163/a-study-to-assess-the-efficacy-and-safety-of-imab362-in-combination-with-nab-paclitaxel-and-gemcitabine-nab-p-gem-as-first-line-treatment-in-subjects-with-claudin-182-cldn182-positive-metastatic-pancreatic-adenocarcinoma

A Study of Zolbetuximab (IMAB362) in Adults With ... Zolbetuximab is thought to work by attaching to CLDN 18.2 in their tumor. This switches on the body's immune system to attack the tumor.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03114-4/fulltext

1532TiP Zolbetuximab with gemcitabine + nab-paclitaxel ( ... GN is a standard-of-care first-line treatment option for patients (pts) with mPC. Poor prognosis and a low 5-year survival rate (<5%) in mPC highlight the ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20467337

Clinical Trials The purpose of this study is to confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM, determine overall survival.

8. patientworthy.com patientworthy.com/2025/10/28/phase-2-gleam-trial-of-zolbetuximab-in-pancreatic-cancer-falls-short-of-primary-endpoint/

Phase 2 GLEAM Trial of Zolbetuximab in Pancreatic ... The randomized, open-label study compared zolbetuximab plus gemcitabine/nab-paclitaxel against the standard gemcitabine/nab-paclitaxel regimen.