What side effects are associated with this type of intervention?

Common side effects of treatments for stomach cancer that involve immune system activation, such as ASP2138, include fatigue, nausea, diarrhea, and skin reactions like rash and pruritus. More serious immune-related adverse events can occur, such as pneumonitis, colitis, hepatitis, endocrinopathies (e.g., thyroid dysfunction), and myocarditis. These side effects result from the immune system attacking normal tissues in addition to the tumor.

What prior FDA approvals exist?

One FDA-approved treatment for stomach cancer that involves immune system activation is pembrolizumab, which is used for PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma. Pembrolizumab is a monoclonal antibody that targets the PD-1 receptor on T-cells, thereby enhancing the immune system's ability to attack tumor cells. While not identical to ASP2138, which targets CLDN18.2 and CD3, pembrolizumab similarly leverages the immune system to combat cancer.

What other types of research exist?

Promising novel alternatives to ASP2138 for stomach cancer patients include: 1) Pembrolizumab (Keytruda) - a PD-1 inhibitor that enhances the immune system's ability to fight cancer cells. 2) Nivolumab (Opdivo) - another PD-1 inhibitor with similar immune-activating properties. 3) Trastuzumab deruxtecan (Enhertu) - an antibody-drug conjugate targeting HER2-positive gastric cancer. 4) Ramucirumab (Cyramza) - a VEGFR2 antagonist that inhibits angiogenesis in tumors. These treatments have shown efficacy in clinical trials and are considered promising options for advanced stomach cancer.

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ASP2138 for Digestive System Cancers

Q: What is the mechanism of action of this treatment?

Common treatments for stomach cancer include targeted therapies, immunotherapies, and traditional chemotherapy. Targeted therapies, such as trastuzumab, focus on specific proteins like HER2 to inhibit tumor growth. Immunotherapies, like immune checkpoint inhibitors (e.g., pembrolizumab), work by blocking proteins that prevent the immune system from attacking cancer cells. ASP2138, a novel treatment under study, binds to CLDN18.2 on tumor cells and CD3 on T-cells, activating the immune system to target and destroy the tumor. These treatments are crucial as they offer more personalized and potentially effective options for patients, especially those with advanced or treatment-resistant stomach cancer.

Phase 1

Recruiting

Research Sponsored by Astellas Pharma Global Development, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central immunohistochemistry (IHC) testing.

Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Must not have

Participant weighs < 40 kg.

Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 21 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called ASP2138 for adults with advanced stomach, gastroesophageal junction, or pancreatic cancer. ASP2138 helps the immune system target and attack cancer cells. The study aims to find a safe and effective dose and monitor any side effects. Participants will receive the drug through an IV or injection and will be closely monitored throughout the study.

Who is the study for?

Adults with advanced stomach, gastroesophageal junction, or pancreatic cancer that can't be removed by surgery or has spread are eligible. They must not be pregnant or breastfeeding and agree to contraception. Their tumors should express CLDN18.2 protein and they should have a life expectancy of at least 12 weeks.

What is being tested?

The trial is testing ASP2138, which targets both the tumor cell and an immune cell protein to direct the immune system against the tumor. It's given as an infusion in two phases: first to find a safe dose by escalating amounts in small groups, then using those doses to see how different cancers respond.

What are the potential side effects?

Potential side effects aren't detailed but may include reactions related to infusions through veins, impacts on organ functions due to immune responses, and general discomfort from treatment such as fatigue or digestive issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor tested positive for CLDN18.2.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am not pregnant, confirmed by a blood test and doctor's evaluation.

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I have been diagnosed with pancreatic cancer.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I weigh less than 40 kg.

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I have severe blockage in my stomach causing vomiting.

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I haven't had serious heart issues like a heart attack or unstable angina in the last 6 months.

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I need treatment for another type of cancer.

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I have a history of lung disease involving the tissue and space around the air sacs.

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I have an active hepatitis B or C infection.

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I do not have significant gastric bleeding or untreated ulcers.

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I had radiotherapy for advanced stomach or pancreatic cancer and still have side effects.

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I had major surgery less than 28 days ago and haven't fully recovered.

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I have brain metastases that are causing symptoms or are unstable.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 21 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 21 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 21 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Dose Escalation)

Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status

Number of participants with Adverse Events (AEs)

+5 more

Secondary study objectives

Change from baseline in claudin (CLDN) 18.2 tumor expression level

Change from baseline in programmed death-ligand 1 (PD-L1) tumor expression level

Change from baseline in serum carbohydrate antigen 19-9 (CA19-9) (pancreatic only) (Phase 1b dose expansion)

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Monotherapy Dose Expansion (Phase 1b) Pancreatic cancerExperimental Treatment1 Intervention

Participants will receive ASP2138 at the candidate RP2D regimens determined in Monotherapy Dose Escalation arm.

Group II: Monotherapy Dose Expansion (Phase 1b) Gastric/GEJ cancerExperimental Treatment1 Intervention

Participants will receive ASP2138 at the candidate RP2D regimens determined in Monotherapy Dose Escalation arm.

Group III: Monotherapy Dose Escalation (Phase 1)Experimental Treatment1 Intervention

A dose escalation design will be used to determine the Maximum Tolerated Dose (MTD) and/ or the Recommended Phase 2 Dose (RP2D) regimens to be further evaluated in the Monotherapy Dose Expansion arms. Monotherapy Dose escalation part consists of six parts (Part A, B, C, D, E, and F), and approximately 86 patients would be enrolled in total. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in each part. The study will open with the Part A dosing schedule, while subsequent cohorts will be opened sequentially or in parallel based upon sponsor review of emerging data.

Group IV: Combination Therapy Dose Escalation (Phase 1) Part I - First line Pancreatic CancerExperimental Treatment5 Interventions

A dose escalation design will be used to determine the MTD and/ or the RP2D regimens to be further evaluated in the Combination Dose Expansion arms. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in combination with mFOLFIRINOX as first line therapy.

Group V: Combination Therapy Dose Escalation (Phase 1) Part H - Second-line Gastric/GEJ CancerExperimental Treatment3 Interventions

Group VI: Combination Therapy Dose Escalation (Phase 1) Part G - First-line Gastric/GEJ CancerExperimental Treatment5 Interventions

A dose escalation design will be used to determine the MTD and/ or the RP2D regimens to be further evaluated in the Combination Dose Expansion arms. In combination dose escalation part G approximately 24 patients would be enrolled in total. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in combination with pembrolizumab and mFOLFOX6 as first line therapy.

Group VII: ASP2138 + mFOLFIRINOX Combination Therapy Dose Expansion (Phase 1b) Pancreatic CancerExperimental Treatment5 Interventions

Participants will receive candidate RP2D regimens of ASP2138 in combination with mFOLFIRINOX as first line therapy in pancreatic cancer determined in Combination Therapy Dose Escalation arm in combination with mFOLFIRINOX as first line therapy in pancreatic cancer.

Group VIII: ASP2138 + Ramucirumab & Paclitaxel Combination Therapy Dose Expansion (Phase 1b) Gastric/GEJ CancerExperimental Treatment3 Interventions

Participants will receive candidate RP2D regimens of ASP2138 in combination with ramucirumab and paclitaxel as second line therapy determined in Combination Therapy Dose Escalation arm.

Group IX: ASP2138 + Pembrolizumab & mFOLFOX6 Combination Therapy Dose Expansion (Phase 1b) Gastric/GEJ CancerExperimental Treatment5 Interventions

Participants will receive candidate RP2D regimens of ASP2138 in combination with pembrolizumab \& mFOLFOX6 as first line therapy determined in Combination Therapy Dose Escalation arm.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3130

Oxaliplatin

2011

Completed Phase 4

~2890

Fluorouracil

2014

Completed Phase 3

~11700

Leucovorin

2005

Completed Phase 4

~6010

Irinotecan

2017

Completed Phase 3

~2590

Ramucirumab

2017

Completed Phase 3

~5050

Paclitaxel

2011

Completed Phase 4

~5450

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for stomach cancer include targeted therapies, immunotherapies, and traditional chemotherapy. Targeted therapies, such as trastuzumab, focus on specific proteins like HER2 to inhibit tumor growth. Immunotherapies, like immune checkpoint inhibitors (e.g., pembrolizumab), work by blocking proteins that prevent the immune system from attacking cancer cells. ASP2138, a novel treatment under study, binds to CLDN18.2 on tumor cells and CD3 on T-cells, activating the immune system to target and destroy the tumor. These treatments are crucial as they offer more personalized and potentially effective options for patients, especially those with advanced or treatment-resistant stomach cancer.

MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma.Upregulation of bone morphogenetic protein 1 is associated with poor prognosis of late-stage gastric Cancer patients.CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach.