Trial Title:
KN026 Plus Chemotherapy ± KN-046 in HER2 Positive Colorectal Cancer and Biliary Carcinoma
NCT ID:
NCT05985707
Condition:
HER2-positive Colorectal Cancer
HER2-positive Biliary Tract Cancer
Conditions: Official terms:
Colorectal Neoplasms
Biliary Tract Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KN026
Description:
KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2
epitopes.
Arm group label:
A
Arm group label:
B
Arm group label:
C
Intervention type:
Drug
Intervention name:
KN046
Description:
KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1 and
CTLA-4 interaction with CD80/CD86.
Arm group label:
B
Arm group label:
C
Intervention type:
Drug
Intervention name:
XELOX
Description:
XELOX is the standard first-line chemotherapy in metastatic colorectal cancer and biliary
duct cancer.
Arm group label:
A
Arm group label:
B
Arm group label:
C
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. 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）.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants are able to comprehend the informed consent information and sign the
informed consent form.
2. Participants ≥ 18 years old, of any gender.
3. 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).
4. 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.
5. 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.
6. LVEF ≥ 50%
(9) 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.
(13) Expected survival of ≥ 3 months. (14) Participants need to receive capecitabine
and oxaliplatin regimen chemotherapy based on clinical assessment.
(15) 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.
(16) Participants are capable and willing to comply with the study protocol,
treatment plan, laboratory tests, and other study-related procedures.
Exclusion Criteria:
1. 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.
2. Ampullary carcinoma.
3. Previous history of receiving any systemic anticancer therapy for metastatic tumors
or participation in interventional clinical trials.
4. 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).
5. Received live vaccines (including attenuated live vaccines) within 28 days before
the first dose.
6. Subjects with interstitial lung disease or requiring oral or intravenous
administration of corticosteroids.
7. 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.
8. 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.
9. 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.
10. History of allogeneic bone marrow or organ transplantation.
11. 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).
12. Pregnant and/or lactating females.
13. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University cancer hospital & institution
Address:
City:
Beijing
Zip:
100142
Country:
China
Contact:
Last name:
Ting Xu, MD
Phone:
18201137836
Email:
xtlmhxt@163.com
Contact backup:
Last name:
Zhenghang Wang, MD
Email:
zhenghang_wang@bjmu.edu.cn
Investigator:
Last name:
Lin Shen
Email:
Principal Investigator
Investigator:
Last name:
Jian Li
Email:
Sub-Investigator
Start date:
August 15, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Peking University Cancer Hospital & Institute
Agency class:
Other
Source:
Peking University Cancer Hospital & Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05985707
