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

Study Identifier:
546C-CL-0201
CT.gov Identifier:
NCT07488676
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
  • Bowel (Colorectal)
  • Non-Small Cell Lung Cancer
  • Ovarian
  • Pancreas
  • Small Cell Lung
  • Gastric
  • Solid Tumor
  • Esophageal
  • Neuroendocrine
  • Bile Duct
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: EXPERIMENTAL: Part 1 - Cohort 1 ASP546C Lower Dose
    • Read More
  • Drug: 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: Drug: ASP546C
  • Drug: Intravenous administration
  • Drug: Other Names: XNW27011
  • Drug: EXPERIMENTAL: Part 1 - Cohort 2 ASP546C Higher Dose
  • Drug: Participants with uLA/m gastroesophageal adenocarcinoma will receive a higher dose of ASP546C intravenously, once Q3W.
  • Drug: EXPERIMENTAL: Part 2 - Cohort 3 ASP546C Higher Dose
  • Drug: Participants with uLA/m pancreatic adenocarcinoma will receive a higher dose of ASP546C intravenously, once Q3W.
  • Drug: EXPERIMENTAL: Part 2 - Cohort 4 ASP546C Higher Dose
  • Drug: 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.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Drew Rasco
    Status
    Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Small Cell Lung
    Gastric
    Solid Tumor
    Esophageal
    Neuroendocrine
    Bile Duct
    Location
    START Los Angeles
    Los Angeles, CA, United States, 90025
    Investigator
    Lasika Seneviratne
    Status
    Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Small Cell Lung
    Gastric
    Solid Tumor
    Esophageal
    Neuroendocrine
    Bile Duct
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Manish Sharma
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Small Cell Lung
    Gastric
    Solid Tumor
    Esophageal
    Neuroendocrine
    Bile Duct
    Location
    START New York (Long Island)
    Lake Success, NY, United States, 11042
    Investigator
    Geraldine O'Sullivan Coyne
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Small Cell Lung
    Gastric
    Solid Tumor
    Esophageal
    Neuroendocrine
    Bile Duct
    Location
    START Mountain Region
    West Valley City, UT, United States, 84119
    Investigator
    Jose Pacheco
    Status
    Will Be Recruiting
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Ovarian
    Pancreas
    Small Cell Lung
    Gastric
    Solid Tumor
    Esophageal
    Neuroendocrine
    Bile Duct