The purpose of this study is to assess the safety and tolerability and preliminary antitumor activity of SKB264 with/without KL-A167 in patients with unresectable locally advanced, recurrent or metastatic TNBC and HR+/HER2- BC .The study is divided into three parts.Part 1(TNBC): exploratory phase of the efficacy and safety of the combination treatment. Part 2(TNBC): The subjects will be randomized to treatment group for SKB264 + KL-A167 or SKB264 . Part 3(HR+/HER2- BC): The subjects will be randomized to treatment group for SKB264 + KL-A167 or SKB264 .
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
175
SKB264 will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle
KL-A167 will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle
Hunan Cancer Hospital
Changsha, Hunan, China
Jiangsu Province Hospital
Nanjing, Jiangsu, China
Incidence and severity of adverse events (AEs)
Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: From baseline up to 30 days after last dose or to the beginning of the new anti-cancer therapy, up to 24 months
Objective Response Rate (ORR)
Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1.
Time frame: From baseline to first documented objective response, up to 24 months
Progression-free survival (PFS)
Progression-free survival (PFS) was defined as the time from baseline to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From baseline to the first documented disease progression or date of death (whichever occurs first), up to 24 months
Duration of response (DOR)
Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR was measured for responding subjects (PR or CR) only.
Time frame: From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 24 months
Disease control rate (DCR)
Disease control rate (DCR) was defined as the sum of complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate. As per RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Time frame: From baseline to date of first documented objective response (CR, PR, and SD), up to 24 months
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB264-ADC, SKB264-TAB and free KL610023
Time frame: Cycles 1-3, 5, 7, 9, and 11, every 6 cycles starting from Cycle 17 Day 1: pre-dose, post-dose (each cycle is 14 days), up to 24 months
Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB264-ADC, SKB264-TAB and free KL610023
Time frame: Cycles 1-3, 5, 7, 9, and 11, every 6 cycles starting from Cycle 17 Day 1: pre-dose, post-dose (each cycle is 14 days), up to 24 months
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of KL-A167
Time frame: Cycles 1-3, 5, 7, 9, and 11, every 6 cycles starting from Cycle 17 Day 1: pre-dose, post-dose (each cycle is 14 days), up to 24 months
Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of KL-A167
Time frame: Cycles 1-3, 5, 7, 9, and 11, every 6 cycles starting from Cycle 17 Day 1: pre-dose, post-dose (each cycle is 14 days), up to 24 months
Anti-drug Antibodies (ADA) for SKB264 and KL-A167
Time frame: Cycles 1-3, 5, 7, 9, and 11, every 6 cycles starting from Cycle 17 Day 1: within 1 h before infusion of SKB264 (each cycle is 14 days), up to 24 months
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