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.
* Cohorts 1 and 2 (gastroesophageal adenocarcinoma) only: Participant has a HER2 negative tumor.
* 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 per local requirements.
* If participant is negative for HBsAg, but hepatitis B core antibody (HBcAb) 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 \> 450 msec (male participant); QTc interval \> 470 msec (female participant).
* 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.
