Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma Pancreatic Adenocarcinoma
Conditions
Interventions
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 wit
Sponsors
Daniel Lionarons
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant has a histologically confirmed diagnosis of gastroesophageal (gastric/ gastroesophageal junction [GEJ] /esophageal) adenocarcinoma, pancreatic adenocarcinoma, or pan-tumor (cholangiocarcinoma, colorectal adenocarcinoma, non-small cell lung cancer [NSCLC] [adenocarcinoma], small cell lung cancer [SCLC], ovarian mucinous carcinoma or invasive breast cancer [estrogen receptor [ER]/ progesterone receptor [PR]+ human epidermal growth factor receptor 2[HER2]-; ER/PR-HER2+; ER/PR+HER2+ [triple positive]; ER/PR-HER2- [triple negative]). 2. Participant has radiologically confirmed unresectable locally advanced or metastatic (uLA/m) gastroesophageal (gastric/GEJ/esophageal) adenocarcinoma, pancreatic adenocarcinoma or pan-tumor within 28 days prior to the first dose of study intervention. 3. Cohorts 1 to 3 only: Participant has measurable disease according to Response Evaluation Criteria in Solid Tumours (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. 4. 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. 5. Participant's tumor expresses claudin (CLDN)18.2. 6. Participant has received at least 1 line of therapy for uLA/m disease. 7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Participant has a predicted life expectancy >/= 12 weeks. 9. Female participant: - Is not pregnant and at least 1 of the following conditions apply: a. Not a women of childbearing potential (WOCBP) b. WOCBP who has a negative urine or serum pregnancy test at screening (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. - 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. - 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. 10. 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. - 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. - Must not donate sperm during the treatment period and for 5 half-lives (45 days) plus 3 months after final investigational study intervention administration. 11. Participant must meet all of the criteria based
Exclusion criteria
Exclusion criteria: 1. Cohorts 1, 2 and 3 only: Participant's disease is of the non-adenocarcinoma histology or mixed histology containing adenocarcinoma. 2. 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. 3. Participant has complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting. 4. 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. 5. Participant has significant bleeding disorders or has had vasculitis within 3 months prior to the first dose of study intervention. 6. Participant has a history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of study intervention. 7. 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. 8. Participant has a past or current mental illness that is difficult to control. 9. 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. 10. 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) and/or hepatitis B surface antibody (HBsAb) positive, a hepatitis B deoxyribonucleic acid (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 ribo nucleic acid (RNA) test results, is eligible. - Participant treated for HCV with undetectable viral load results is eligible. 11. Participant has an active infection requiring systemic therapy that has not completely resolved within 7 days prior to the first dose of study intervention. 12. 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. 13. 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. 14. Participant has any adverse event (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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Objective response rate (ORR), defined as the proportion of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) (investigator-assessed per RECIST v1.1) - Pharmacokinetics (PK), as determined by serum concentrations of antidrug antibody Conjugate (ADC) and PK parameters - AEs, vital signs, ECOG performance status and safety laboratory assessments (NCI CTCAE v6.0) | — |
Secondary
| Measure | Time frame |
|---|---|
| - ORR, defined as the proportion of participants who have a BOR of CR or PR (investigator-assessed per RECIST v1.1). - Disease control rate (DCR), defined as the proportion of participants with a BOR of CR, PR or stable disease (SD) (investigator-assessed per RECIST v1.1) - Duration of response (DOR), defined as the time from the date of the first response (CR/PR) until the date of radiologic disease progression (investigator-assessed per RECIST v1.1) or date of death from any cause, whichever is earlier - Progression-free survival (PFS), defined as the time from the date of first dose until the date of radiologic disease progression (investigator-assessed per RECIST v1.1) or death from any cause, whichever is earlier - Overall survival (OS), defined as the time from the date of first dose until the documented date of death from any cause - AEs, vital signs, ECOG performance status and safety laboratory assessments (NCI CTCAE v6.0) - CLDN18.2 changes by immunohistochemistry (IHC) in baseline and on-treatment tumor samples - PK parameters of ADC, unconjugated payload and total antibody: o Concentration at the end of infusion (CEOI) o Area under the concentration-time curve from 0 to 21 days (AUC 0-21d) o Trough concentration (Ctrough) o Time to maximum concentration (tmax) o Terminal elimination half-life (t1/2) o Clearance (CL) o Volume of Distribution at Steady State (Vss) - Incidence of ADAs against ASP546C (total antibody and ADC) | — |
Countries
Japan, United States
Contacts
Public ContactWang Medical Information Center
Astellas Pharma Inc.
Outcome results
None listed