Colorectal CancerPhase 2NCT05985109
KN 046 Plus Regorafenib in MSS Metastatic Colorectal Cancer
A Phase 2 study testing KN046 and regorafenib in people with Colorectal Cancer, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial summary
The study is an interventional Phase II clinical trial aiming to optimize immunotherapy strategies for microsatellite-stable colorectal cancer. We will include three types of metastatic colorectal cancer patients: those without liver metastasis, or carrying BRAF V600E mutation, or unable to tolerate chemotherapy as… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- KN046 and regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 26 Oct 2023to 30 Sep 2026
- Phase
- Phase 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
- I01. Subjects are able to comprehend the informed consent form, voluntarily participate, and sign the informed consent form.
- I02. Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
- I03. Histologically confirmed colorectal adenocarcinoma, including signet ring cell carcinoma and mucinous adenocarcinoma.
- I04. 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.
- I05. ECOG performance status of 0 or 1. I06. Expected survival ≥3 months. I07. Archived tumor tissue samples or freshly obtained tumor tissue samples are available.
- I08. 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.
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- I09. Subjects have the ability and willingness to comply with the study protocol's visits, treatment plan, laboratory tests, and other study-related procedures.
- I10. Within the first 7 days of initial dosing, subjects should have good organ function:
- HGB ≥ 80g/L NEU ≥ 1.010^9/L PLT ≥ 7510^9/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
- I11. For each cohort, the previous treatment history must meet the following conditions:
- Cohort A: pMMR/MSS mCRC with no BRAF V600E mutation, who failed fluoropyrimidine, oxaliplatin, and irinotecan treatments, and without definitive active liver metastases at enrollment (judged by the investigator based on medical history and imaging).
- Cohort B: pMMR/MSS mCRC with BRAF V600E mutation, who failed fluoropyrimidine, oxaliplatin, and irinotecan treatments.
- Cohort C: MSS mCRC that has not intolerant or unsuitable for or refuse to receive standard first-line or second-line chemotherapy.
Who cannot join
- E01. 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.
- E02. 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.
- E03. 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.
- E04. 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).
- E05. 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.
- E06. Subjects who have received live vaccines (including attenuated live vaccines) within 28 days before the first dose.
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- E07. Subjects with interstitial lung disease or a history of non-infectious pneumonia requiring oral or intravenous corticosteroid treatment.
- E08. 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.
- E09. 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.
- E10. 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.
- E11. 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).
- E12. History of allogeneic bone marrow or organ transplantation. E13. 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).
- E14. Pregnant and/or lactating females. E15. 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.
- E16. Previous treatment with any immune checkpoint inhibitors or T-cell co-stimulatory drugs, including but not limited to PD-1/PD-L1, CTLA-4, LAG3, and other immune checkpoint inhibitors, therapeutic vaccines, etc.
- E17. Previous treatment with regorafenib.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Multi-cohort Clinical Study Evaluating The Efficacy and Safety of KN046 in Combination With Regorafenib for Metastatic Microsatellite-Stable Colorectal Cancer: a Phase II Multi-cohort Study
The study is an interventional Phase II clinical trial aiming to optimize immunotherapy strategies for microsatellite-stable colorectal cancer. We will include three types of metastatic colorectal cancer patients: those without liver metastasis, or carrying BRAF V600E mutation, or unable to tolerate chemotherapy as their initial or second-line treatment. The participants will receive a combination treatment of regorafenib and KN046 which is a PD-L1/CTLA-4 bispecific antibody. Treatment efficacy and safety profile would be evaluated in this study.
- Conditions
- Colorectal Cancer
- Being tested
- KN046, regorafenib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN046Drug
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.
regorafenibDrug
Regorafenib is a multi-target tyrosine kinase inhibitors and is one of the standard third-line therapy in mCRC
| Study group | Role | What they receive |
|---|---|---|
| Non-liver metastasis cohort | Experimental | Arm A will include microsatellite-stable metastatic colorectal cancer patients who have no active liver metastasis. Patients are required to have received prior 5-Fu， oxaliplatin, and irinotecan treatment before enrollment. Receives: Drug: KN046; Drug: regorafenib |
| BRAF V600E mutant cohort | Experimental | Arm B will include microsatellite-stable metastatic colorectal cancer patients who have BRAF V600E mutation. Patients are required to have received prior 5-Fu， oxaliplatin, and irinotecan treatment before enrollment. Receives: Drug: KN046; Drug: regorafenib |
| Front-line therapy cohort | Experimental | Arm C will include microsatellite-stable metastatic colorectal cancer patients who are unable or refuse to receive standard first-line or second-line treatment. Receives: Drug: KN046; Drug: regorafenib |
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) will be 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 (5)
Disease control rate
Disease control rate (defined as CR+PR+SD) will be 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
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
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
treatment-related adverse event
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.
Measured: Informed consent to 30 days after last dose of treatment
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 start26 Oct 2023
- Primary completion30 Sep 2026
- Study completion30 Sep 2026
Why it stopped: The study was stopped early due to lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lin Shen, Peking University Cancer Hospital & Institute
- Investigators
- Lin Shen, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05985109
- Sponsor's protocol ID
- CGOG-KREC-01
- Status last verified
- Oct 2026
- First submitted
- 2 Aug 2023
- Last updated
- 3 Nov 2026
- 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 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multi-cohort Clinical Study Evaluating The Efficacy and Safety of KN046 in Combination With Regorafenib for Metastatic Microsatellite-Stable Colorectal Cancer: a Phase II Multi-cohort Study
- ClinicalTrials.gov ID
- NCT05985109
- Acronym / sponsor ID
- CGOG-KREC-01
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped early due to lack of efficacy.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 26 Oct 2023 (actual)
- Primary completion
- 30 Sep 2026 (actual)
- Study completion
- 30 Sep 2026 (actual)
- 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 study is an interventional Phase II clinical trial aiming to optimize immunotherapy strategies for microsatellite-stable colorectal cancer. We will include three types of metastatic colorectal cancer patients: those without liver metastasis, or carrying BRAF V600E mutation, or unable to tolerate chemotherapy as their initial or second-line treatment. The participants will receive a combination treatment of regorafenib and KN046 which is a PD-L1/CTLA-4 bispecific antibody. Treatment efficacy and safety profile would be evaluated in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Non-liver metastasis cohort | Experimental | Drug: KN046, Drug: regorafenibArm A will include microsatellite-stable metastatic colorectal cancer patients who have no active liver metastasis. Patients are required to have received prior 5-Fu， oxaliplatin, and irinotecan treatment before enrollment. |
| BRAF V600E mutant cohort | Experimental | Drug: KN046, Drug: regorafenibArm B will include microsatellite-stable metastatic colorectal cancer patients who have BRAF V600E mutation. Patients are required to have received prior 5-Fu， oxaliplatin, and irinotecan treatment before enrollment. |
| Front-line therapy cohort | Experimental | Drug: KN046, Drug: regorafenibArm C will include microsatellite-stable metastatic colorectal cancer patients who are unable or refuse to receive standard first-line or second-line treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- I01. Subjects are able to comprehend the informed consent form, voluntarily participate, and sign the informed consent form.
- I02. Subjects are ≥18 years old on the day of signing the informed consent form, with no gender restrictions.
- I03. Histologically confirmed colorectal adenocarcinoma, including signet ring cell carcinoma and mucinous adenocarcinoma.
- I04. 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.
- I05. ECOG performance status of 0 or 1. I06. Expected survival ≥3 months. I07. Archived tumor tissue samples or freshly obtained tumor tissue samples are available.
Key exclusion criteria (15 listed)
- E01. 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.
- E02. 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.
- E03. 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.
- E04. 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).
- E05. 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.
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 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. | Drug | BRAF V600E mutant cohort, Front-line therapy cohort, Non-liver metastasis cohort |
| regorafenibRegorafenib is a multi-target tyrosine kinase inhibitors and is one of the standard third-line therapy in mCRC | Drug | BRAF V600E mutant cohort, Front-line therapy cohort, Non-liver metastasis cohort |
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) will be reported based on investigator's evaluation.
5 secondary outcomes
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
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
Overall survival
Time frame: 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
Results and safety
The study was stopped early (reason given: The study was stopped early due to lack of efficacy.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- 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. This study is not recruiting at the moment.
Lin Shen principal investigator
Peking University Cancer Hospital & Institute
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 KN046 and regorafenib in people with Colorectal 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 13 inclusion and 15 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: stopped early, as of the sponsor's last update on 3 Nov 2026. 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?
The study was stopped early (reason given: The study was stopped early due to lack of efficacy.). Results are not available in the source record.
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?
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 3 Nov 2026.