Triple-negative Breast Cancer
Conditions
Brief summary
This is an open-label, phase Ib/II, multi-center study to evaluate efficacy and safety of KN046 alone or in combination with nab-paclitaxel in subjects with locally advanced unresectable or metastatic triple negative breast cancer (TNBC). The study is composed of dose escalation and expansion parts. Every subject will subject tumor tissue used for biomarker evaluation. Each subject will receive KN046 or in combination with nab-paclitaxel untill confirmed progressive disease, unacceptable toxicity or withdrawal of informed consent whichever occurs first.
Interventions
BIOLOGICALKN046
KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle
DRUGNab-paclitaxel
Nab-paclitaxel at dose level of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of 28-day cycle
Sponsors
Jiangsu Alphamab Biopharmaceuticals Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent; * Age of 18 or above; * Histology confirmed locally advanced unresectable or metastatic triple-negative breaset cancer; * (KN046 monotherapy) failed at least one prior anthracycline and taxane containing systemic treatment, (KN046 plus nab-paclitaxel) systemic treatment naive; * Measurable disease at baseline; * ECOG 0-1; * Adequate organ functions.
Exclusion criteria
* Untreated active CNS metastasis or leptomeningeal metastasis; * Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment; * Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management; * Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent; History of uncontrolled intercurrent illness; Known severe hypersensitivity reactions to antibody drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IRC assessed objective response | From Day 1 to PD, assessed up to 12 months after last patient last dose | Objective response is defined as complete response (CR) or partial response (PR), as determined by the independent review committee using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (\<) 10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD |
| IRC assessed duration of response | From Day 1 to PD, assessed up to 12 months after last patient last dose | Duration of response is defined as the time period from the date of initial independent review committee assessed CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to \<10mm for nodal TLs/ non-TLs. PR is defined as \>/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as \>/=20% relative increase and \>/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS rate at 6 and 12 months | From Day 1 to disease progression (PD) or death from any cause, assessed up to 12 months after last patient last dose | PFS is defined as the time from Day 1 to the first occurrence of PD, as determined by the independent review committee or investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (\>/=) 20 percent (%) relative increase and \>/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. PFS rate at 6 and 12 months is defined as percentage of subjects who are alive without progressive disease or death at 6 and 12 months |
| Frequency and severity of treatment emergent adverse events | From Day 1 to 90 days after last dose of KN046, through study completion, an average of 1 year | Treatment emergent adverse event is defined as those events with onset days occurring during the on-treatment period till 90 days after last dose of KN046 or if the worsening of an event is during the on-treatment period till 90 days after last dose of KN046 |
| Percentage of subjects with anti-drug antibodies | Day 1 (pre-dose) to 90 days after last dose of KN046, through study completion, an average of 1 year | ADA is defined as human anti-drug antibodies |
Countries
China
Outcome results
None listed