- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06099821
KN046 Plus Regorafenib or Apatinib in MSI-H Digestive System Cancers Resistant to PD-1/PD-L1 Blockade
October 25, 2023 updated by: Lin Shen, Peking University Cancer Hospital & Institute
A Phase II Clinical Study Evaluating The Efficacy and Safety of KN046 in Combination With Regorafenib or Apatinib for Microsatellite Instability-High Digestive System Cancers Resistant to PD-1/PD-L1 Blockade
The study is an interventional phase II clinical trial aiming to evaluate the efficacy and safety of KN046, a PD-L1 and CTLA-4 bispecific antibody, in combination with regorafenib or apatinib for microsatellite instability-high digestive system cancers resistant to PD-1/PD-L1 blockade.
KN046 plus regorafenib will be given for patients with colorectal cancers, and KN046 plus apatinib will be given for patients with gastric cancers (including esophageal-gastric junction cancers) and other kinds of digestive system cancers.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
39
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Zhenghang Wang
- Phone Number: 01088196561
- Email: zhenghang_wang@bjmu.edu.cn
Study Contact Backup
- Name: Ting Xu
- Phone Number: 18201137836
- Email: xtlmhxt@163.com
Study Locations
-
-
-
Beijing, China
- Recruiting
- Peking university cancer hospital
-
Contact:
- Zhenghang Wang, Dr
-
Contact:
- Ting Xu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Subjects are able to comprehend the informed consent form, voluntarily participate, and sign the informed consent form.
- Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
- Histologically confirmed digestive system cancers.
- According to RECIST 1.1 criteria, there should be at least one measurable or evaluable lesion at baseline. If the subject has only one measurable or evaluable lesion at baseline, the lesion must not have been exposed to radiotherapy previously, or there must be evidence of significant progression after radiotherapy treatment completion.
- ECOG performance status of 0 or 1.
- Expected survival ≥3 months.
- Archived tumor tissue samples or freshly obtained tumor tissue samples are available.
- Female subjects of childbearing potential or male subjects with partners of childbearing potential agree to use highly effective contraception from 7 days before the first dose until 120 days after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.
- Subjects have the ability and willingness to comply with the study protocol's visits, treatment plan, laboratory tests, and other study-related procedures.
- Within the first 7 days of initial dosing, subjects should have good organ function:
- HGB ≥ 80g/L, NEU ≥ 1.0*10^9/L, PLT ≥ 75*10^9/L, Cr≤1.5×ULN or CrCl≥50mL/min(Cockcroft-Gault method), TBiL ≤ 1.5×ULN, ALT and AST ≤3 ×ULN; for patients with liver metastasis ALT and AST ≤5 ×ULN, urine protein <2+;,if urine protein ≥ 2+, 24 hour urinary protein quantity <2g; INR, APTT, PT ≤ 1.5 ×ULN
- dMMR/MSI-H cancers resistant to PD1/PDL1 blockade. MSI status should be confirmed by PCR or NGS. If MSI status by PCR and NGS were not consistent, or no enough tissue were available for PCR or NGS testing, whether to enroll this patient should be determine by investigators.
Exclusion Criteria:
- Subjects with untreated active brain metastases or meningeal metastases; if the subject's brain metastases have been treated and the metastases are stable (brain imaging at least 4 weeks before the first dose shows stable lesions, and there is no evidence of new neurological symptoms or the neurological symptoms have returned to baseline), then enrollment is allowed.
- Subjects with a history of gastrointestinal perforation or fistula within 6 months before the first dose. If the perforation or fistula has been treated with resection or repair, and the disease is judged to be recovered or improved by the investigator, then enrollment is allowed.
- Subjects who have received any other interventional clinical trial or any other antitumor treatment within 28 days or 5 half-lives before the first dose (whichever is shorter). Palliative radiotherapy for bone metastases to relieve symptoms is permitted.
- Subjects who have undergone major surgery within 28 days before the first dose (e.g., major abdominal or thoracic surgery; excluding drainage, diagnostic puncture, or peripheral vascular access replacement).
- Subjects who require systemic corticosteroids (≥10 mg/day prednisone or equivalent) or immunosuppressive therapy for a continuous 7-day period within 14 days before the first dose. Inhaled or locally applied steroids and physiological replacement doses of steroids due to adrenal insufficiency are allowed. Short-term (≤7 days) corticosteroids for prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reaction caused by exposure to allergens) are allowed.
- Subjects who have received live vaccines (including attenuated live vaccines) within 28 days before the first dose.
- Subjects with interstitial lung disease or a history of non-infectious pneumonia requiring oral or intravenous corticosteroid treatment.
- Subjects with active autoimmune diseases requiring systemic treatment within 2 years before the start of the study or those considered at risk of recurrence or planned treatment for autoimmune diseases as judged by the investigator. Exclusions include a) skin diseases that do not require systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema); b) hypothyroidism caused by autoimmune thyroiditis, requiring stable doses of hormone replacement therapy; c) type 1 diabetes requiring stable doses of insulin replacement therapy; d) childhood asthma fully resolved with no need for intervention in adulthood; e) the investigator judges that the disease will not relapse without external triggering factors.
- Subjects with a history of other malignant tumors within 5 years, excluding cured skin squamous cell carcinoma, basal cell carcinoma, non-invasive bladder carcinoma, localized low-risk prostate cancer (defined as stage ≤T2a, Gleason score ≤6, and prostate-specific antigen (PSA) ≤10 ng/mL (if measured) in patients who have undergone curative treatment and have no biochemical recurrence of prostate-specific antigen (PSA)), in situ cervical/breast carcinoma, or Lynch syndrome.
- Subjects with uncontrolled comorbidities, including but not limited to: a) active HBV or HCV infection; b) subjects who are HBsAg positive and/or HCV antibody positive during screening must undergo HBV DNA and/or HCV RNA testing. Only subjects with HBV DNA ≤500 IU/mL (or ≤2000 copies/mL) and/or HCV RNA negative can be enrolled; HBV DNA monitoring will be at the discretion of the investigator based on the subject's condition during the trial; c) known HIV infection or AIDS history; d) active tuberculosis; e) active infection or systemic use of anti-infective drugs for more than 1 week within 28 days before the first dose; fever of unknown cause within 2 weeks before the first dose; f) uncontrolled hypertension (resting blood pressure ≥160/100 mmHg), symptomatic congestive heart failure (NYHA II-IV), unstable angina or myocardial infarction within 6 months, or the presence of QTc prolongation or the risk of arrhythmia (baseline QTc >470 msec <Fridericia method correction>, difficult-to-correct hypokalemia, long QT syndrome, atrial fibrillation with resting heart rate >100 bpm, or severe valvular heart disease); g) active bleeding that cannot be controlled after medical treatment.
- Toxicity from previous antitumor treatments has not recovered to Grade ≤2 (NCI-CTCAE v5.0) or baseline, except for alopecia, skin pigmentation (allowed at any level), and immune-related adverse reactions requiring physiological replacement (e.g., hypothyroidism, hypopituitarism, type 1 diabetes).
- History of allogeneic bone marrow or organ transplantation.
- Previous history of allergic reactions, hypersensitivity reactions, or intolerance to antibody drugs (e.g., severe allergic reactions, immune-mediated hepatotoxicity, immune-mediated thrombocytopenia, or anemia).
- Pregnant and/or lactating females.
- Other conditions that, in the investigator's opinion, may affect the safety or compliance of the study drug treatment, including but not limited to moderate to large pleural/ascites/pericardial effusion, uncorrectable pleural/ascites/pericardial effusion, intestinal obstruction or subacute intestinal obstruction, psychiatric disorders, etc.
- Previous treatment with any immune checkpoint inhibitors in combination with anti-VEGF tyrosine kinase inhibitor, including but not limited to Regorafenib, Apatinib, Sulfatinib and Anlctinib.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients resistant to PD1/PDL1 blockade
Patients with microsatellite instability-high digestive system cancers resistant to PD-1/PD-L1 blockade
|
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody that blocks both PD-L1 interaction with PD-1 and CTLA-4 interaction with CD80/CD86.
Regorafenib is a multi-target tyrosine kinase inhibitors and is one of the standard third-line therapy in mCRC
Apatinib is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer.
It has been also reported to have anti-tumor efficacy in other kinds of digestive system cancers.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
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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
|
Overall survival (OS) is defined as the time from the date of first dose to the date of death from any cause.
|
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
|
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) will be reported based on investigator's evaluation.
|
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
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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
|
Disease control rate (defined as CR+PR+SD) will be reported based on investigator's evaluation.
|
Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose
|
treatment-related adverse event
Time Frame: Informed consent to 30 days after last dose of treatment.
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A treatment-related adverse event (TRAE) 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.
TRAEs were graded using National Cancer Institute (NCI)-CTCAE version 5.0.
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Informed consent to 30 days after last dose of treatment.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: lin Shen, Peking University Cancer Hospital & Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 25, 2023
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Study Registration Dates
First Submitted
October 20, 2023
First Submitted That Met QC Criteria
October 20, 2023
First Posted (Actual)
October 25, 2023
Study Record Updates
Last Update Posted (Actual)
October 26, 2023
Last Update Submitted That Met QC Criteria
October 25, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CGOG-KRAC-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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