A Study of ASP546C in Adults With Gastroesophageal Cancer, Pancreatic Cancer or Other Solid Tumors

A Phase 1b/2 Open-label Study to Assess the Safety and Efficacy of ASP546C in Participants With CLDN18.2-expressing Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma, Pancreatic Adenocarcinoma or Other Solid Tumor Types

This study will help find the most suitable dose of ASP546C in people with gastric cancer, gastroesophageal junction (GEJ) cancer, pancreatic cancer, and other specific solid tumors. GEJ is where the food pipe (esophagus) joins the stomach.

This study is in 2 parts. In both parts of the study, ASP546C will be given once in 3-week cycles. It will be given slowly through a tube into a vein. This is called an infusion.

In Part 1, people with gastric cancer or GEJ cancer can take part. They will receive an infusion of either a higher dose or a lower dose of ASP546C.

In Part 2, people with pancreatic cancer or who have one of the other solid tumors can take part. Part 2 doesn't include people with gastric cancer or GEJ cancer. All people in this part of the study will receive an infusion of the higher dose of ASP546C.

People will visit the clinic on certain days to receive ASP546C and have health checks. The number of visits and checks done during the study will depend on the health of each person and whether they are still receiving infusions of ASP546C.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma; Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
• Intervention / Treatment: Drug: ASP546C

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development, Inc; Phone Number: 800-888-7704; Email: Astellas.registration@astellas.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • START Los Angeles
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • New York
    • Lake Success, New York, United States, 10042
      • Recruiting
      • START New York
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Oncology - Austin
    • Houston, Texas, United States, 77054
      • Recruiting
      • Next Oncology - Houston
    • Irving, Texas, United States, 75039
      • Recruiting
      • NEXT Oncology - Dallas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START San Antonio
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has a histologically confirmed diagnosis of gastroesophageal (gastric/GEJ/esophageal) adenocarcinoma, pancreatic adenocarcinoma, or pan-tumor (cholangiocarcinoma, colorectal adenocarcinoma, NSCLC [adenocarcinoma], SCLC, ovarian mucinous carcinoma or invasive breast cancer [ER/PR+HER2-; ER/PR-HER2+; ER/PR+HER2+ (triple positive); ER/PR-HER2- (triple negative)].
• Participant has radiologically confirmed uLA/m gastroesophageal (gastric/GEJ/esophageal) adenocarcinoma, pancreatic adenocarcinoma or pan-tumor within 28 days prior to the first dose of study intervention.
• Cohorts 1 to 3 only: Participant has measurable disease according to RECIST v1.1 within 28 days prior to the first dose of study intervention. For participants with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
• Cohort 4 only: Participant has radiologically evaluable disease (measurable and/or non-measurable) according to RECIST v1.1, within 28 days prior to the first dose of study intervention. For participants with only 1 evaluable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
• Participant's tumor expresses CLDN18.2.
• Participant has received at least 1 line of therapy for uLA/m disease.
• Participant has an ECOG performance status of 0 or 1.
• Participant has a predicted life expectancy >= 12 weeks.

• Female participant is not pregnant and at least 1 of the following conditions apply:

  • Not a women of childbearing potential (WOCBP)
  • WOCBP who has a negative urine or serum pregnancy test at screening (Specific to Japan: with a medical interview), and agrees to follow the contraceptive guidance from the time of informed consent through at least 5 half-lives (45 days) plus 6 months after final investigational study intervention administration.
• Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 5 half-lives (45 days) plus 6 months after final investigational study intervention administration.
• Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period and for 5 half-lives (45 days) plus 6 months after final investigational study intervention administration.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 5 half-lives (45 days) plus 3 months after final investigational study intervention administration.
• Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 5 half-lives (45 days) plus 3 months after final investigational study intervention administration.
• Male participant must not donate sperm during the treatment period and for 5 half-lives (45 days) plus 3 months after final investigational study intervention administration.
• Participant must meet all of the criteria based on the locally analyzed laboratory tests collected within 14 days prior to the first dose of study intervention. In case of multiple local laboratory tests within this period, the most recent data should be used.
• Participant is willing to provide or has sufficient tumor tissue for central biomarker assessment.
• Participant agrees not to participate in another interventional study while receiving study intervention in the present study.

Exclusion Criteria:

• Cohorts 1, 2 and 3 only: Participant's disease is of the non-adenocarcinoma histology or mixed histology containing adenocarcinoma.

• Cohorts 1, 2 and 3 only: Participant has received > 2 prior lines of therapy for uLA/m disease.

  • Participants in Cohort 4 (pan-tumor) may enroll regardless of the number of prior lines of therapy, if they are not eligible for, decline, or do not have any available standard of care treatment options.
• Participant has complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
• Participant has significant gastric bleeding or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to the first dose of study intervention and/or an untreated peptic ulcer disease that would preclude the participant from participation.
• Participant has significant bleeding disorders or has had vasculitis within 3 months prior to the first dose of study intervention.
• Participant has a history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of study intervention.
• Participant has symptomatic, untreated brain metastases or meningeal carcinomatosis (carcinomatous meningitis) from the primary malignancy. A participant with stable central nervous system metastases for > 3 months without need of steroids for >= 2 weeks prior to the first dose of study intervention is eligible.
• Participant has a past or current mental illness that is difficult to control.
• Participant has unresolved pneumonitis or a history of non-infectious pneumonitis such as immune-related pneumonitis or radiation-induced pneumonitis for which the participant is taking glucocorticoids or needed glucocorticoids within 6 months prior to the first dose of study intervention.

• Participant has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or hepatitis C infection. Screening for these infections should be conducted if indicated per local requirements.

  • If participant is negative for HBsAg, but hepatitis B core antibody (HBcAb) and/or hepatitis B surface antibody (HBsAb) positive, a hepatitis B DNA test will be performed; if the test is positive, the participant will be excluded.
  • Participant with positive hepatitis C virus (HCV) serology, but negative HCV RNA test results, is eligible.
  • Participant treated for HCV with undetectable viral load results is eligible.
• Participant has an active infection requiring systemic therapy that has not completely resolved within 7 days prior to the first dose of study intervention.
• Participant has a malignancy for which treatment is required, has a history of another malignancy within the past 5 years, except malignancies for which participant received curative therapy without recurrence for the last 5 years (e.g., adequately resected non-melanoma skin cancer, localized prostate cancer), or had treatment for carcinoma in situ.
• Participant has clinically significant third spacing (large amount of pleural fluid or ascites) that requires frequent percutaneous draining or requires placement of a drainage catheter for adequate control.
• Participant has any AE from prior antitumor treatments that has not yet recovered to grade 0 or 1 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v6.0 (except alopecia).
• Participant has an active autoimmune disease or other medical condition that has required high dose systemic steroids at the time of screening.
• Participant has known peripheral neuropathy > grade 1 (except when the sole neurological abnormality is absence of deep tendon reflexes).
• Participant has sinusoidal obstruction syndrome, formerly known as veno-occlusive disease; if present, should be stable or improving.

• Participant has significant cardiovascular disease, including any of the following:

  • Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to the first dose of study intervention.
  • History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes), cardiac arrhythmias requiring anti-arrhythmic medications (a participant with rate controlled atrial fibrillation for > 1 month prior to the first dose of study intervention is eligible) or obligate use of cardiac pacemaker.
  • QTc interval > 470 msec
  • Documented history or family history of congenital long QT syndrome.
• Participant has ongoing or previous interstitial lung disease, active diverticulitis or solid organ or stem cell transplant.
• Participant has a serious non-healing wound or bone fracture within 28 days prior to study intervention.
• Participant has had a major surgical procedure within 28 days prior to the first dose of study intervention and has not completely recovered from the surgical procedure <= 14 days prior to the first dose of study intervention.
• Participant has received chemotherapy, immunotherapy or investigational therapy <= 14 days prior to the first dose of study intervention and has not recovered from any related toxicity. Palliative radiotherapy is allowed and must be completed > 14 days prior to the first dose of study intervention.
• Participant has received prior CLDN18.2 ADC. Prior treatment with CLDN18.2 monoclonal antibody or bi-specific T-cell engager is allowed.
• Participant has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Participant has a known or suspected hypersensitivity to ASP546C or any components of the formulation used.
• Participant has a clinically significant disease or comorbidity that in the opinion of the investigator may adversely affect the safe delivery of treatment within this study or make the participant unsuitable for study participation.
• Cohorts 1 and 2 (gastroesophageal adenocarcinoma) only: Participant has known HER2 positive status defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +. ISH positive is defined as HER2/ chromosome enumeration probe 17 (CEP17) ratio ≥ 2.0 or an average HER2 copy number ≥ 6.0 signals/cell.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Cohort 1 ASP546C Lower Dose; Participants with unresectable locally advanced or metastatic (uLA/m) gastroesophageal adenocarcinoma will receive a lower dose of ASP546C intravenously, once every 3 weeks (Q3W).	Drug: ASP546C; Intravenous administration; Other Names: XNW27011
Experimental: Part 1 - Cohort 2 ASP546C Higher Dose; Participants with uLA/m gastroesophageal adenocarcinoma will receive a higher dose of ASP546C intravenously, once Q3W.	Drug: ASP546C; Intravenous administration; Other Names: XNW27011
Experimental: Part 2 - Cohort 3 ASP546C Higher Dose; Participants with uLA/m pancreatic adenocarcinoma will receive a higher dose of ASP546C intravenously, once Q3W.	Drug: ASP546C; Intravenous administration; Other Names: XNW27011
Experimental: Part 2 - Cohort 4 ASP546C Higher Dose; Participants with pan-tumor (cholangiocarcinoma, colorectal adenocarcinoma, NSCLC, SCLC, ovarian mucinous carcinoma or invasive breast cancer) will receive a higher dose of ASP546C intravenously, once Q3W.	Drug: ASP546C; Intravenous administration; Other Names: XNW27011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective Response Rate (ORR) per Investigator-assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR is defined as the proportion of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) as per investigator assessment per RECIST v1.1.	Up to 36 Months
Part 1: Pharmacokinetics (PK) of ASP546C Antibody-drug Conjugate (ADC): Serum Concentrations of Antibody-drug Conjugate	ADC concentrations will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1: PK of ASP546C ADC: Maximum Concentration (Cmax)	Cmax will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1: PK of ASP546C ADC: Area Under the Serum Concentration-time Curve from Time Zero to 21Days (AUC0-21d)	AUC0-21d will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1: Number of participants with Adverse events (AEs)	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.	Up to 39 Months
Part 1: Number of Participants with Vital Sign Abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to 39 Months
Part 1: Number of Participants with Laboratory Value Abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to 39 Months
Part 1: Number of Participants at Each Grade of Eastern Cooperative Oncology Group (ECOG) Performance Status Scores	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 39 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: ORR per Investigator-assessed per RECIST v1.1	ORR is defined as the proportion of participants who have a BOR of CR or PR as per investigator assessment per RECIST v1.1.	Up to 36 Months
Part 1 and Part 2: Disease Control Rate (DCR) per Investigator-assessed per RECIST v1.1	DCR defined as the proportion of participants with a BOR of CR, PR or stable disease (SD) as per investigator assessment per RECIST v1.1.	Up to 36 Months
Part 1 and Part 2: Duration of Response (DOR) per Investigator-assessed per RECIST v1.1	DOR is defined as the time from the date of the first response (CR/PR) until the date of radiologic disease progression as per investigator assessment per RECIST v1.1 or date of death from any cause, whichever is earlier.	Up to 36 Months
Part 1 and Part 2: Progression Free Survival (PFS) per Investigator-assessed per RECIST v1.1	PFS is defined as the time from the date of first dose until the date of radiologic disease progression as per investigator assessment per RECIST v1.1 or death from any cause, whichever is earlier.	Up to 39 Months
Part 1 and Part 2: Overall Survival (OS)	OS is defined as the time from the date of first dose until the documented date of death from any cause	Up to 39 Months
Part 2: Number of Participants with AEs	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.	Up to 39 Months
Part 2: Number of Participants with Vital Sign Abnormalities and/or AEs	Number of participants with potentially clinically significant vital sign values.	Up to 39 Months
Part 2: Number of Participants with Laboratory Value Abnormalities and/or AEs	Number of participants with potentially clinically significant laboratory values.	Up to 39 Months
Part 2: Number of Participants at Each Grade of ECOG Performance Status Scores	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 39 Months
Part 1 and Part 2: Change from baseline in Expression Levels of Claudin 18.2 (CLDN18.2)	Comparison of CLDN18.2 expression at baseline versus on-treatment tumor biopsies will be performed.	Baseline and up to Day 58
Part 1 and Part 2: PK of ASP546C ADC: Concentration at the End of Infusion (CEOI)	CEOI will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: CEOI	CEOI will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: CEOI	CEOI will be recorded from the PK serum samples collected.	Up to 39 Months
Part 2: PK of ASP546C ADC: AUC0-21d	AUC0-21d will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: AUC0-21d	AUC0-21d will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: AUC0-21d	AUC0-21d will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C ADC: Trough Concentration (Ctrough)	Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: Ctrough	Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: Ctrough	Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C ADC: Time of Maximum Concentration (tmax)	tmax will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: tmax	tmax will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: tmax	tmax will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C ADC: Terminal Elimination Half-life (t1/2)	t1/2 will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: t1/2	t1/2 will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: t1/2	t1/2 will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C ADC: Clearance (CL)	CL will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: CL	CL will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: CL	CL will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C ADC: Volume of Distribution at Steady State (Vss)	Vss will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Unconjugated Payload: Vss	Vss will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: PK of ASP546C Total Antibody: Vss	Vss will be recorded from the PK serum samples collected.	Up to 39 Months
Part 1 and Part 2: Number of Participants with all Anti-drug Antibodies (Total Antibody and ADC) Against ASP546C	Number of participants with anti-drug antibodies will be reported.	Up to 22 Months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Study Physician, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cholangiocarcinoma; Pancreatic Adenocarcinoma; Small cell lung cancer (SCLC); Colorectal adenocarcinoma; Invasive breast cancer; Claudin 18.2; Non-small cell lung cancer (NSCLC) (adenocarcinoma); Ovarian mucinous carcinoma; ASP546C; Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Adenocarcinoma; Small Cell Lung Carcinoma
• Other Study ID Numbers: 546C-CL-0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No