This is a first-in-human, 2-part study to investigate the safety, tolerability, pharmacokinetics and efficacy of KM257 by itself and combined with selected chemotherapy agents in patients with advanced HER2-positive or expressing cancers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
232
Part 1a dose escalation: There will be 3 increasing dose levels (3mg/kg,6mg/kg,12mg/kg). Patients will be intravenously administrated with one dose of KM257, QW for continuous cycles of 21 consecutive days for each cycle. The dosing interval may be adjusted during the study based on emerging data from this trial. Part 1b dose expansion: Part1b:For cohort 1 and cohort2, KM257 will be given at the RP2D identified in Part1a; For cohort 3 to 7:KM257 will be given combined with one of the following selected drug combination: Drug: Capecitabine Combination therapy with KM257 - Cohort 3 Drug: Paclitaxel or Docetaxel or Irinotecan Combination therapy with KM257 - Cohort 4 Drug: Gemcitabine+Cisplatin Combination therapy with KM257 - Cohort 5 Drug: Gemcitabine+Cisplatin or Carboplatin Combination therapy with KM257 - Cohort 6 Drug:Carboplatin+Paclitaxel Combination therapy with KM257 - Cohort 7
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Maximum tolerated dose (MTD) (Part 1a)
Determine maximum tolerated dose (MTD) of KM257.
Time frame: Up to 3 weeks
Recommended phase 2 dose (RP2D) (if has) (Part 1a)
Determine recommended phase 2 dose (RP2D) of KM257.
Time frame: Up to 3 weeks
Number of patients with adverse events.(Part 1a)
Number of patients who experienced an adverse event
Time frame: Up to 8 months.
Objective response rate (ORR) (Part 1b)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 2-3 years.
Area under the concentration versus time curve of KM257 in plasma (AUC) (Part 1a and Part1b).
To determine the AUC of KM257.
Time frame: Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.
Maximum serum concentration (Cmax) of KM257(Part 1a and Part 1b ).
To determine the maximum serum concentration (Cmax) of KM257.
Time frame: Up to 63days for Part 1a; Up to 63 days for Part1b.
Time of Maximum observed serum concentration (Tmax) of KM257 (Part1 and Part1b ) .
To determine the Tmax of KM257.
Time frame: Up to 63days for Part 1a; Up to 63days for Part1b.
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Serum Half-life (T-HALF) of KM257. (Part1a and Part1b)
To determine the t1/2 of KM257.
Time frame: Up to 63days.
Frequency and titer of anti-KM257 antibody. (Part1a and Part1b)
To determine the immunogenicity of KM257.
Time frame: up to 8months for Part1a and up to 2-3 years for Part1b.
Objective response rate (ORR) (Part 1a)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 8months.
Progression free survival (PFS) (Part 1a and Part 1b)
To determine the PFS by investigator.
Time frame: up to 2-3 years.
Disease control rate (DCR) (Part 1a and Part 1b)
To determine the DCR by investigator.
Time frame: up to 2-3 years.
Overall survival (OS) (Part1a and Part1b )
To determine the OS by investigator.
Time frame: up to 2-3 years.
Number of patients with adverse events (Phase 1b)
Incidence of AE as assessed by CTCAE 5.0
Time frame: up to 2-3 years.