Triple-negative Breast CancerPhase 1/2NCT03872791

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

A Phase 1/2 study testing KN046 and Nab-paclitaxel in people with Triple-negative Breast Cancer, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 12 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Triple-negative Breast Cancer
What is being tested?: KN046 and Nab-paclitaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 52 participants
Where: 12 sitesChina
Study dates: 30 May 2019to 27 Oct 2022
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

China12 sites

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality
JiLin Cancer Hospital
Changchun, Jilin
Hunan Cancer Hospital
Changsha, Hunan
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang
LiaoCheng People's Hospital
Liaocheng, Shandong
Nantong Tumor Hospital
Nantong, Jiangsu
Liaoning Cancer Hospital
Shenyang, Liaoning
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian
Henan Cancer Hospital
Zhengzhou, Henan
Zibo Municipal Hospital
Zibo, Shandong

Other trials in China

About this study

Official title: 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

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.

Conditions: Triple-negative Breast Cancer
Being tested: KN046, Nab-paclitaxel
Medical subject headings: Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KN046Biological
KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle
Nab-paclitaxelDrug
Nab-paclitaxel at dose level of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of 28-day cycle

Study groups in NCT03872791
Study group	Role	What they receive
KN046	Experimental	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 Receives: Biological: KN046
KN046 plus nab-paclitaxel	Experimental	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 Receives: Biological: KN046; Drug: Nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: From Day 1 to PD, assessed up to 12 months after last patient last dose

Secondary outcomes (3)

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
Measured: 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
Measured: 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
Measured: Day 1 (pre-dose) to 90 days after last dose of KN046, through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 May 201927 Oct 2022

First posted13 Mar 2019
Study start30 May 2019
Primary completion16 Aug 2022
Study completion27 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Triple-negative Breast CancerStudies of the same condition, open and under way.
More trials run by Jiangsu Alphamab Biopharmaceuticals Co., LtdThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03872791
Sponsor's protocol ID: KN046-203
Status last verified: Jun 2023
First submitted: 7 Mar 2019
Last updated: 8 Jun 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: all IPD that underlie results in a publication

Publications

Li Q, Liu J, Zhang Q, Ouyang Q, Zhang Y, Liu Q, Sun T, Ye F, Zhang B, Xia S, Zhang B, Xu B. The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial. Nat Commun. 2024 Feb 3;15(1):1015. doi: 10.1038/s41467-024-45160-y.
PubMed 38310192

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03872791
Acronym / sponsor ID: KN046-203
Conditions: Triple-negative Breast Cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: Jiangsu Alphamab Biopharmaceuticals Co., LtdIndustry (pharma, biotech, devices)
Study start: 30 May 2019 (actual)
Primary completion: 16 Aug 2022 (actual)
Study completion: 27 Oct 2022 (actual)
First posted: 13 Mar 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
KN046	Experimental	Biological: KN046Subjects 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
KN046 plus nab-paclitaxel	Experimental	Biological: KN046, Drug: Nab-paclitaxelSubjects 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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;

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KN046KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle	Biological	KN046, KN046 plus nab-paclitaxel
Nab-paclitaxelNab-paclitaxel at dose level of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of 28-day cycle	Drug	KN046 plus nab-paclitaxel

Primary outcome

IRC assessed objective response
Time frame: 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
Time frame: 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

3 secondary outcomes

PFS rate at 6 and 12 months
Time frame: 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
Time frame: 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
Time frame: Day 1 (pre-dose) to 90 days after last dose of KN046, through study completion, an average of 1 year

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2023.
Derived from this study: PubMed 38310192Li Q, Liu J, Zhang Q, Ouyang Q, Zhang Y, Liu Q, Sun T, Ye F, Zhang B, Xia S, Zhang B, Xu B. The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial. Nat Commun. 2024 Feb 3;15(1):1015. doi: 10.1038/s41467-024-45160-y.
Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KN046 and Nab-paclitaxel in people with Triple-negative Breast Cancer, run by Jiangsu Alphamab Biopharmaceuticals Co., Ltd at 12 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

IRC assessed objective response (time frame: From Day 1 to PD, assessed up to 12 months after last patient last dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03872791, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2023.