Patients had histologically locally confirmed measurable HR+/HER2 MBC and 2-4 prior systemic chemotherapy regimens for metastatic disease. (Neo)adjuvant therapy for early-stage disease qualified as one of the required prior chemotherapy regimens if the development of unresectable, locally advanced, or metastatic disease occurred within 12 months of therapy (early relapse). Patients must have previously received at least one taxane, at least one anticancer hormonal treatment, and at least one CDK4/6i.

Patients had metastatic triple-negative breast cancer (mTNBC) that had progressed following 2 prior standard chemotherapy regimens (no upper limit) for unresectable, locally advanced, or metastatic disease, and included a taxane (any setting). Per protocol, patients were also eligible after only one prior regimen in the metastatic setting if their disease recurred within 12 months of completing (neo)adjuvant therapy.

Patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens (no upper limit) for unresectable, locally advanced or metastatic disease; previous therapy had to include a taxane (for any indication). Patients had to have triple-negative breast cancer according to standard American Society of Clinical OncologyCollege of American Pathologists criteria.

Patients 18 years of age with mSCLC who had relapsed or were refractory to at least one prior standard line of therapy for metastatic disease, and with measurable tumors by CT, were enrolled. They were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and other eligibility as described in the phase I trial (25). Previous therapy had to be completed at least 2 weeks before enrollment.

Patients were >18 years of age with metastatic cancer [cervical, clear-cell renal, CRC, epithelial ovarian, endometrial, esophageal, gastric, hepatocellular, CRPC, pancreatic ductal adenocarcinoma, squamous cell head and neck, thyroid, urothelial (UC) cancer; glioblastoma multiforme; mTNBC or non-mTNBC; and SCLC or NSCLC] who had relapsed after or were refractory to at least one prior standard therapeutic regimen.

Patients 18 years with mNSCLC who had measurable disease and progressed after at least one line of therapy for stage IV disease were enrolled. Requirements included Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow and hepatic and renal function, and other eligibility criteria as described in the phase I trial. Prior systemic therapy had to be completed at least 4 weeks before enrollment.

Patients 18 years of age who had mTNBC refractory to or relapsed after at least one standard line of therapy since diagnosis and measurable disease by computed tomography scan (or magnetic resonance imaging). patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and prior toxicities at study entry of grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Patients with brain metastasis were excluded, unless treated and without progression, and were not receiving high-dose corticosteroids for at least 4 weeks.

Eligibility requires confirmed advanced/metastatic solid tumors, ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function, excluding recent cancer therapy, unresolved toxicities (>Grade 1), major surgery, active infections, uncontrolled comorbidities (CNS, cardiovascular, hepatic, GI), HIV/hepatitis B/C, drug hypersensitivity, or pregnancy risk. Exclusions also cover conditions jeopardizing protocol compliance.

The study evaluates treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded by CTCAE v5.0, occurring from first dose until 30 days post-treatment. Key efficacy measures include Objective Response Rate (ORR) by Independent Central Review (ICR) using RECIST 1.1 criteria, with CR/PR definitions for tumor assessment, analyzed in the TNBC Target Population during phase 2 over 49 months.

Eligibility requires confirmed advanced/metastatic solid tumors, ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function, excluding recent cancer therapy, unresolved toxicities (>Grade 1), major surgery, active infections, uncontrolled comorbidities (CNS, cardiovascular, hepatic, GI), HIV/hepatitis B/C, drug hypersensitivity, or pregnancy risk. Exclusions also cover conditions jeopardizing protocol compliance.

The study evaluates treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded by CTCAE v5.0, occurring from first dose until 30 days post-treatment. Key efficacy measures include Objective Response Rate (ORR) by Independent Central Review (ICR) using RECIST 1.1 criteria, with CR/PR definitions for tumor assessment, analyzed in the TNBC Target Population during phase 2 over 49 months.

The primary endpoint was progression-free survival (PFS) assessed by IRC and investigators per RECIST 1.1, measuring time from randomization to PD or death over 24 months. Key secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DoR), all evaluated over 24 months using RECIST 1.1 criteria. Quality of life was assessed via NCC-BC-A scale, while safety covered AEs, SAEs (CTCAE 5.0), pharmacokinetic parameters (clearance, volume of distribution), and ADA incidence.

Eligible patients were adults (≥18 years) with HR+/HER2- breast cancer failing ≥1 line of chemotherapy, measurable lesions per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions included recent anti-cancer therapies (within 4 weeks), unresolved toxicities (>Grade 1), major surgery within 4 weeks, prior topoisomerase I/TROP2 inhibitors, untreated CNS metastases, active infections, uncontrolled comorbidities (cardiovascular, GI, HIV, hepatitis B/C), or hypersensitivity to irinotecan/excipients.

Key inclusion criteria include adults ≥18 years with histologically confirmed TNBC (metastatic or relapsed), no prior systemic therapy for advanced disease, PD-L1-negative or PD-L1-positive post-relapse, measurable lesions, ECOG 0-1, and adequate organ function. Exclusion criteria cover recent investigational drugs, prior topoisomerase I/TROP2 therapy, severe comorbidities (CNS metastases, cardiovascular disease, uncontrolled infections, gastrointestinal disorders), drug hypersensitivity, and pregnancy/lactation.

The primary endpoints include Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) and Overall Survival (OS). PFS is defined as the time from randomization to disease progression per RECIST 1.1 or death, while OS measures time from randomization to any-cause death, with follow-up periods of approximately 28 and 41 months, respectively.

Secondary endpoints encompass investigator-assessed PFS, Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DoR), and Time to Response (TTR) evaluated by both BICR and investigator. Additional assessments include Quality of Life via NCC-BC-A scale, safety analysis for AEs/SAEs, pharmacokinetic parameters (clearance, volume of distribution), and immunogenicity measurement (anti-drug antibodies), with evaluations spanning approximately 28 months.

Eligible patients require histopathologically confirmed salivary gland carcinoma with specific biomarker testing, good ECOG status (0-1), measurable lesions per RECIST 1.1, and adequate organ function. Exclusions include treatment allergies, recent major surgery/vaccination, active infections, major cardiovascular diseases, uncontrolled comorbidities, or pregnancy/breastfeeding.

Key eligibility: Adults with taxane-pretreated TNBC (ER/PR<1%, HER2-negative) eligible for ICC chemotherapy (ECOG 0-1, measurable lesions per RECIST 1.1). Exclusions: active CNS metastases, prior TROP-2/topoisomerase I inhibitors, HIV/HBV/HCV positivity, recent anti-tumor treatments (4 weeks), major surgery (4 weeks), or pregnancy. Requires adequate organ function and tumor tissue availability.

Key eligibility: Adults (18-75) with advanced solid tumors (TNBC/UC/NSCLC/SCLC/etc.) refractory to standard therapy (ECOG 0-1, measurable disease per RECIST 1.1). Exclusions: prior Trop-2 therapy, irinotecan hypersensitivity, uncontrolled comorbidities (cardiac/respiratory/diabetes), active infections (HBV/HCV/HIV), recent anti-tumor treatments (4 weeks), major surgery (4 weeks), or pregnancy. Requires adequate organ function and tumor tissue availability.

FDA018-ADC will be administered via IV infusion on Day 1, 15 and 22 of a 35-Day cycle (Cycle 1) and on Day 1, 15 and 22 of a 35-Day cycle (Cycle 1) and on Day 1 and 8 of a 21-day cycle (Cycle 2 ~ Cycle 5) in dose escalation phase, and on Day 1 and 8 of a 21-day cycle (Cycle 1 ~ Cycle 6) in dose expansion phase, and Day 1 and 8 of a 21-day cycle in follow-up period until disease progression, unacceptable toxicity or death.

The median PFS for all 86 patients was 3.60 months (95% CI,2.00 months to 4.00 months), with 16.8% (14 of 86) remaining progression free for at least 6 months, including three patients who maintained this status for at least 1 year. The median OS was 6.90 months (95% CI, 5.70 months to 7.80 months), with 24.41% (21 of 86) surviving for at least 1 year, including three patients who survived at least 2 years (one for 3 years).

Eligible participants must have metastatic colorectal adenocarcinoma (prior irinotecan-treated, ECOG 0-1, CEA >5 ng/mL, measurable disease) with adequate organ function. Exclusions include pregnancy, active CNS metastases, bulky disease (>10 cm), HIV/HBV/HCV positivity, significant cardiac/respiratory disease, or concurrent conditions impairing study compliance. Prior malignancies require ≥3-year disease-free interval (exceptions: non-melanoma skin/cervical cancers).

Eligible patients must have metastatic colorectal adenocarcinoma (prior treatment failure, ECOG 0-1, CEA >5 ng/mL, measurable disease) and adequate organ function. Exclusions include pregnancy, active CNS metastases (unless stable post-treatment), CEA >1000 ng/mL (pre-MTD), grade 3 anorexia/vomiting, uncontrolled autoimmune disease (except stable conditions), HIV/HBV/HCV positivity, recent cardiac/respiratory events, or other conditions impairing study compliance. Prior malignancies require ≥3-year disease-free interval (exceptions: non-melanoma skin/cervical cancers).

Eligible patients include adults ≥18 with histologically confirmed metastatic colorectal adenocarcinoma, prior irinotecan treatment, ECOG 0-1, adequate organ function, and measurable disease. Exclusions cover pregnancy, uncontrolled comorbidities, active infections, recent malignancies, and conditions interfering with study compliance per investigator judgment.