Locally advanced or metastatic malignant solid tumors
Conditions
Interventions
In this study, ASP2998 will be given to humans for the first time. ASP2998 will either be given by itself, or given together with one or more of standard cancer treatments pembrolizumab, carboplatin a
Sponsors
Gupta Anumeha
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. For the ASP2998 monotherapy dose escalation (excluding urothelial and non-small cell lung cancer [NSCLC] tumor-specific backfill participants), the following criteria apply: - Participant has a confirmed diagnosis of locally advanced unresectable or metastatic solid tumors. - Participant has progressed on, is ineligible for, or has refused all available standard therapies (no limit to the number of prior treatment regimens). - Prior exposure to TROP2, stimulator of interferon genes (STING) agonist or topoisomerase I (TopI) directed therapy is allowed. - Participant must have one of the following malignancies: o Urothelial carcinoma o NSCLC o Gastric/ gastroesophageal junction (GEJ) cancer o Breast cancer (human epidermal growth factor receptor 2 [HER2]-negative; local testing for HER2 status is acceptable). - For all tumor types, any component of neuroendocrine histology is ineligible. 2. For the ASP2998 monotherapy dose expansion (including the tumor-specific backfill participants from the monotherapy dose escalation), the following criteria apply: a. NSCLC second line (2L)+ Monotherapy Dose Expansion Cohort(s) - Participant has locally advanced unresectable or metastatic NSCLC with known programmed cell death ligand-1 (PD-L1) status, without actionable oncogenic alteration (AGA), according to local testing. - Participant must have histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic NSCLC that has progressed on or after receiving platinum-based chemotherapy and/or checkpoint inhibitors according to local/regional standard of care. - Participant is also eligible if there is disease progression within 12 months of receiving neoadjuvant or adjuvant therapy for resectable disease. o Participant must be eligible to receive treatment in 2L+ setting. - Participant must have had no more than 3 prior lines of therapy. - No prior exposure to TROP2, STING agonist or TopI directed therapy is allowed. b. Urothelial Carcinoma 2L+ Monotherapy Dose Expansion Cohort(s) - Participant must have histologically or cytologically confirmed diagnosis of urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter or urethra) in locally advanced unresectable or metastatic setting that has progressed on a combination of enfortumab vedotin and pembrolizumab according to local/regional standard of care. Participant with urothelial carcinoma (transitional cell) with 12 months after completing adjuvant or neoadjuvant therapy for
Exclusion criteria
Exclusion criteria: 1. Participant weighs /= 8% or HbA1c of 7% to /= 2 years - Any other cancer from which the participant has been disease-free for >/= 5 years 8. Participant has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of study intervention. Inhaled or topical steroids and adrenal replacement doses </= 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 9. Participant has jaundice or known current active liver disease from any cause, including hepatitis A (HAV) immunoglobulin M (IgM) positive, but testing for hepatitis A viral load in screening is not required), hepatitis B (hepatitis B surface antigen [HBsAg] positive, or hepatitis B virus [HBV] DNA positive if HBsAg is negative and anti-HBs and/or anti- hepatitis B [HBc] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV RNA). NOTE: screening for these infections should be conducted per local requirements. 10. Participant has a known history of human immunodeficiency virus (HIV) infection with acquired immunodeficiency syndrome (AIDS)-related complications. HIV testing will be conducted per local requirements. 11. Participant has
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse event (TEAEs) - Clinical laboratory tests - Vital signs - ECGs - Physical examinations - ECOG performance status | — |
Secondary
| Measure | Time frame |
|---|---|
| - Objective response rate (ORR), duration of response (DOR) and disease control rate (DCR) per RECIST v1.1 - Progression-free survival (PFS) per RECIST v1.1 - Overall survival (OS) - Selected pharmacokinetic(s) (PK) parameters of ASP2998 total antibody (TAb) in plasma: area under the concentration-time curve from the time of dosing to 21 days after dosing (AUC21d), maximum concentration (Cmax), trough concentration (Ctrough) and time to maximum concentration (tmax), as applicable - Incidence rate, expression levels and change of TROP2 expression in tumor - Changes in cluster of differentiation (CD8) T-cell lymphocytes in paired biopsies | — |
Countries
Japan, United States
Contacts
Public ContactInformation Center Medical
Astellas Pharma Inc.
Outcome results
None listed