A Study of KN046 in Subjects With Locally Advanced or Metastatic Triple-negative Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ib/II Study to Evaluate Efficacy, Safety and Tolerability of KN046 Monotherapy or in Combination With Nab-paclitaxel in Subjects With Triple-negative Breast Cancer

Conditions
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Triple-negative Breast Cancer

Intervention / Treatment
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* Biological: KN046
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KN046<br>Subjects will receive KN046 at a dose of 3 mg/kg or 5 mg/kg via intravenous infusion on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity or completion of 2 years of treatment | Biological: KN046<br>* KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle<br>|
| Experimental: KN046 plus nab-paclitaxel<br>Subjects will receive KN046 at a dose of 3 mg/kg or 5 mg/kg via intravenous infusion on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity or completion of 2 years of treatment Subjects will receive nab-paclitaxel at a dose of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity | Biological: KN046<br>* KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle<br>Drug: Nab-paclitaxel<br>* Nab-paclitaxel at dose level of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IRC assessed objective response | 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 | From Day 1 to PD, assessed up to 12 months after last patient last dose | 
| IRC assessed duration of response | 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 | From Day 1 to PD, assessed up to 12 months after last patient last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS rate at 6 and 12 months | 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 | From Day 1 to disease progression (PD) or death from any cause, assessed up to 12 months after last patient last dose | 
| Frequency and severity of treatment emergent adverse events | 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 | From Day 1 to 90 days after last dose of KN046, through study completion, an average of 1 year | 
| Percentage of subjects with anti-drug antibodies | ADA is defined as human anti-drug antibodies | Day 1 (pre-dose) to 90 days after last dose of KN046, through study completion, an average of 1 year |