HER2-positive Colorectal CancerPhase 2NCT05985707
KN026 Plus Chemotherapy ± KN-046 in HER2 Positive Colorectal Cancer and Biliary Carcinoma
A Phase 2 study testing KN026, KN046 and XELOX in people with HER2-positive Colorectal Cancer and HER2-positive Biliary Tract Cancer, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial summary
The goal of this Interventional clinical trial is to learn about the efficacy and safety of KN026 and chemotherapy ± KN046 in HER2-positive metastatic colorectal cancer and biliary tract cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Colorectal Cancer, HER2-positive Biliary Tract Cancer
- What is being tested?
- KN026, KN046 and XELOX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 15 Aug 2023to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants are able to comprehend the informed consent information and sign the informed consent form.
- Participants ≥ 18 years old, of any gender.
- Cohorts A and B: Histologically confirmed unresectable HER2-positive metastatic colorectal cancer, meeting the following criteria: a) Previously untreated with systemic anti-tumor therapy, or the time from (neo)adjuvant chemotherapy completion to disease recurrence > 6 months; b) Gene sequencing shows wild-type RAS and BRAF (participants' previous KRAS and BRAF test results are acceptable).
- Cohort C: Histologically confirmed unresectable HER2-positive biliary tract cancer, including intrahepatic or extrahepatic bile duct cancer or gallbladder cancer: a) Previously untreated with systemic anti-tumor therapy; b) If previously received (neo)adjuvant radiotherapy, the time from treatment completion to disease recurrence is > 6 months.
- HER-2 positive defined as a) HER2 IHC 3+; b) HER2 IHC 2+ with HER2 amplification (HER2/CEP17 > 2.0 by ISH method)； c) HER copy number > 6 by next-generation sequencing using tumor tissue or circulating tumor DNA.
- LVEF ≥ 50%
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- Within 7 days before the first administration, hepatic function should meet the following criteria:
- Total bilirubin ≤ 1.0 x ULN (≤ 1.5 x ULN for subjects with Gilbert's syndrome or liver metastases)
- Transaminases (ALT/AST) ≤ 1.5 x ULN (≤ 3 x ULN for subjects with liver metastases) (10) Within 7 days before the first administration, renal function should be as follows:
- Serum creatinine ≤ 1.5 x ULN
- Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula) (11) Within 7 days before the first administration, bone marrow function should meet the following criteria:
- Hemoglobin ≥ 90 g/L
- Absolute neutrophil count ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L (12) TSH within the normal range; if TSH is abnormal, free T3 and free T4 should be within the normal range.
- Expected survival of ≥ 3 months. (14) Participants need to receive capecitabine and oxaliplatin regimen chemotherapy based on clinical assessment.
- Female participants of childbearing potential or male participants with partners of childbearing potential must agree to use effective contraception from 7 days before the first dose until 24 weeks after the last dose. Female participants of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.
- Participants are capable and willing to comply with the study protocol, treatment plan, laboratory tests, and other study-related procedures.
Who cannot join
- Subjects with untreated active brain metastases or leptomeningeal metastases; if subjects have received treatment for brain metastases and the lesions are stable (stable brain imaging for at least 4 weeks before the first dose with no evidence of new or enlarging brain lesions and no new neurological symptoms or stable neurological symptoms at baseline), they are allowed to be enrolled.
- Ampullary carcinoma.
- Previous history of receiving any systemic anticancer therapy for metastatic tumors or participation in interventional clinical trials.
- Within 14 days before the first dose, the subject requires a continuous 7-day treatment of systemic corticosteroids (≥10 mg/day prednisone or equivalent of other corticosteroids) or immunosuppressive agents; exceptions are inhaled or locally applied corticosteroids or physiological replacement doses of corticosteroids for adrenal insufficiency. Short-term (≤7 days) corticosteroids are allowed for prevention (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
- Received live vaccines (including attenuated live vaccines) within 28 days before the first dose.
- Subjects with interstitial lung disease or requiring oral or intravenous administration of corticosteroids.
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- History or current presence of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's granulomatosis (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune hepatitis, systemic sclerosis (scleroderma), Hashimoto's thyroiditis (except under certain circumstances as outlined below), autoimmune vasculitis, and autoimmune neurological disorders (such as Guillain-Barre syndrome). The following conditions are exempted: type 1 diabetes, stable hypothyroidism on hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), and psoriasis or vitiligo not requiring systemic treatment.
- History of another malignant tumor within 5 years before the first dose, except for cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle-invasive bladder cancer, localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6, and prostate-specific antigen (PSA) ≤10 ng/mL at diagnosis, and patients who received curative treatment without PSA biochemical recurrence), and in situ cervical/breast cancer.
- Has uncontrolled comorbidities, including but not limited to the following conditions:
- Active HBV or HCV infection.
- Subjects with positive HBsAg and/or HCV antibodies during screening must undergo HBV DNA and/or HCV RNA testing. Subjects with HBV DNA ≤ 500 IU/mL (or ≤ 2000 copies/mL) and/or HCV RNA negative can be enrolled; during the trial, the investigator will decide on monitoring HBV DNA based on the subject's situation.
- Known HIV infection or history of AIDS.
- Active tuberculosis.
- Active infection or systemic use of antimicrobial drugs for more than 1 week within 28 days before the first dose of this study; unexplained fever within 2 weeks before dosing.
- Uncontrolled hypertension (resting blood pressure ≥ 160/100 mmHg), symptomatic heart failure (NYHA class II-IV), unstable angina or myocardial infarction within the past 6 months, or risk of QTc prolongation or arrhythmia (baseline QTc > 470 msec corrected by Fridericia method, difficult-to-correct hypokalemia, long QT syndrome, resting heart rate > 100 bpm with atrial fibrillation, or severe valvular heart disease).
- Active bleeding that cannot be controlled even with medical intervention.
- History of allogeneic bone marrow or organ transplantation.
- History of allergic reactions, hypersensitivity, or intolerance to antibody-based drugs; history of significant drug allergies (e.g., severe allergic reactions, immune-mediated hepatotoxicity, immune-mediated thrombocytopenia, or anemia).
- Pregnant and/or lactating females.
- Other conditions that, in the opinion of the investigator, may affect the safety or compliance of the study drug treatment, including but not limited to moderate to large pleural/peritoneal/pericardial effusion, difficult-to-correct pleural/peritoneal/pericardial effusion, intestinal obstruction or subacute intestinal obstruction, psychiatric disorders, etc.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Peking University cancer hospital & institution
Beijing, State*, 100142
Ting Xu, MD, 18201137836, xtlmhxt@163.com
Zhenghang Wang, MD, zhenghang_wang@bjmu.edu.cn
About this study
Official title: The Efficacy and Safety of KN026 Combination Chemotherapy ± KN046 in HER2-Positive Advanced Colorectal Cancer and Biliary Tract Cancer as First-Line Treatment： a Phase Ⅱ Study
The goal of this Interventional clinical trial is to learn about the efficacy and safety of KN026 and chemotherapy ± KN046 in HER2-positive metastatic colorectal cancer and biliary tract cancer. Participants will receive standard first-line chemotherapy (capecitabine + oxaliplatin) combined with KN026 (a HER2-targeted bispecific antibody) ± KN046 （a PD-L1/CTLA-4 targeted bispecific antibody）.
- Being tested
- KN026, KN046, XELOX
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN026Drug
KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes.
KN046Drug
KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86.
XELOXDrug
XELOX is the standard first-line chemotherapy in metastatic colorectal cancer and biliary duct cancer.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Arm A will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 treatment. Receives: Drug: KN026; Drug: XELOX |
| B | Experimental | Arm B will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment. Receives: Drug: KN026; Drug: KN046; Drug: XELOX |
| C | Experimental | Arm C will include HER2-positive treatment-naive metastatic biliary tract cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment. Receives: Drug: KN026; Drug: KN046; Drug: XELOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Objective response rate (defined as CR+PR) is reported based on investigator's evaluation.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Secondary outcomes (6)
Progression free survival
Progression-free survival (PFS) is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of radiographic progressive disease (PD) or death due to any cause.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Duration of response
Duration of response (DOR) is defined as the time from the date of the first response to the first objective documentation of radiographic progressive disease (PD) or death due to any cause.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Disease control rate
Disease control rate (defined as CR+PR+SD) is reported based on investigator's evaluation.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Time to response
Time to response (TOR) is defined as the time from the date of the first dose to the first objective documentation of radiographic objective response.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Overall survival
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
Measured: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Frequency of adverse events
A treatment-emergent adverse event (TEAE) is defined as any adverse event not present prior to the initiation of drug treatment or any adverse event already present that worsens in intensity or frequency following exposure to the drug treatment. TEAEs were graded using National Cancer Institute (NCI)-CTCAE version 4.03.
Measured: From the date of signing the informed consent form up to 30 (+7) days after last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start15 Aug 2023 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shen Lin, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05985707
- Sponsor's protocol ID
- HERCKER-01
- Status last verified
- Aug 2023
- First submitted
- 2 Aug 2023
- Last updated
- 21 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of KN026 Combination Chemotherapy ± KN046 in HER2-Positive Advanced Colorectal Cancer and Biliary Tract Cancer as First-Line Treatment： a Phase Ⅱ Study
- ClinicalTrials.gov ID
- NCT05985707
- Acronym / sponsor ID
- HERCKER-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 15 Aug 2023 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 14 Aug 2023 (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.
The goal of this Interventional clinical trial is to learn about the efficacy and safety of KN026 and chemotherapy ± KN046 in HER2-positive metastatic colorectal cancer and biliary tract cancer. Participants will receive standard first-line chemotherapy (capecitabine + oxaliplatin) combined with KN026 (a HER2-targeted bispecific antibody) ± KN046 （a PD-L1/CTLA-4 targeted bispecific antibody）.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: KN026, Drug: XELOXArm A will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 treatment. |
| B | Experimental | Drug: KN026, Drug: KN046, Drug: XELOXArm B will include HER2-positive treatment-naive metastatic colorectal cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment. |
| C | Experimental | Drug: KN026, Drug: KN046, Drug: XELOXArm C will include HER2-positive treatment-naive metastatic biliary tract cancer patients, and the patients in this cohort will receive XELOX and KN026 + KN046 treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Participants are able to comprehend the informed consent information and sign the informed consent form.
- Participants ≥ 18 years old, of any gender.
- Cohorts A and B: Histologically confirmed unresectable HER2-positive metastatic colorectal cancer, meeting the following criteria: a) Previously untreated with systemic anti-tumor therapy, or the time from (neo)adjuvant chemotherapy completion to disease recurrence > 6 months; b) Gene sequencing shows wild-type RAS and BRAF (participants' previous KRAS and BRAF test results are acceptable).
- Cohort C: Histologically confirmed unresectable HER2-positive biliary tract cancer, including intrahepatic or extrahepatic bile duct cancer or gallbladder cancer: a) Previously untreated with systemic anti-tumor therapy; b) If previously received (neo)adjuvant radiotherapy, the time from treatment completion to disease recurrence is > 6 months.
- HER-2 positive defined as a) HER2 IHC 3+; b) HER2 IHC 2+ with HER2 amplification (HER2/CEP17 > 2.0 by ISH method)； c) HER copy number > 6 by next-generation sequencing using tumor tissue or circulating tumor DNA.
Key exclusion criteria (20 listed)
- Subjects with untreated active brain metastases or leptomeningeal metastases; if subjects have received treatment for brain metastases and the lesions are stable (stable brain imaging for at least 4 weeks before the first dose with no evidence of new or enlarging brain lesions and no new neurological symptoms or stable neurological symptoms at baseline), they are allowed to be enrolled.
- Ampullary carcinoma.
- Previous history of receiving any systemic anticancer therapy for metastatic tumors or participation in interventional clinical trials.
- Within 14 days before the first dose, the subject requires a continuous 7-day treatment of systemic corticosteroids (≥10 mg/day prednisone or equivalent of other corticosteroids) or immunosuppressive agents; exceptions are inhaled or locally applied corticosteroids or physiological replacement doses of corticosteroids for adrenal insufficiency. Short-term (≤7 days) corticosteroids are allowed for prevention (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
- Received live vaccines (including attenuated live vaccines) within 28 days before the first dose.
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 |
|---|---|---|
| KN026KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. | Drug | A, B, C |
| KN046KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86. | Drug | B, C |
| XELOXXELOX is the standard first-line chemotherapy in metastatic colorectal cancer and biliary duct cancer. | Drug | A, B, C |
Primary outcome
Overall response rate
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Objective response rate (defined as CR+PR) is reported based on investigator's evaluation.
6 secondary outcomes
Progression free survival
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Duration of response
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Disease control rate
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Time to response
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Overall survival
Time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
Frequency of adverse events
Time frame: From the date of signing the informed consent form up to 30 (+7) days after last dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KN026, KN046 and XELOX in people with HER2-positive Colorectal Cancer and HER2-positive Biliary Tract Cancer, run by Peking University Cancer Hospital & Institute at 1 site 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 17 inclusion and 20 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: opening soon, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jian Li (13601310849, oncogene@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2023.