NCT05985109招募中2 期
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
Peking University Cancer Hospital & Institute1 个研究点 分布在 1 个国家目标入组 98 人开始时间: 2023年10月26日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Overall response rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 colorectal adenocarcinoma, including signet ring cell carcinoma and mucinous adenocarcinoma.
- •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
- •Expected survival ≥3 months. I
- •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
- •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.
排除标准
- •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. E
- •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. E
- •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 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.
- •Previous treatment with regorafenib.
研究组 & 干预措施
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.
干预措施: KN046 (Drug)
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.
干预措施: regorafenib (Drug)
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.
干预措施: KN046 (Drug)
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.
干预措施: regorafenib (Drug)
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.
干预措施: KN046 (Drug)
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.
干预措施: regorafenib (Drug)
结局指标
主要结局
Overall response rate
时间窗: 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.
次要结局
- Disease control rate(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Duration of response(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- treatment-related adverse event(Informed consent to 30 days after last dose of treatment)
- Progression free survival(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
- Overall survival(Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 24 months post-dose)
研究者
Shen Lin
Professor
Peking University Cancer Hospital & Institute
研究点 (1)
Loading locations...
相似试验
终止
2 期
Safety, Immune and Tumor Response to a Multi-component Immune Based Therapy (MKC1106-MT) for Patients With MelanomaStage III MelanomaStage IV MelanomaNCT01026051Mannkind Corporation5
已完成
2 期
Safety and Efficacy Therapy of Gemcitabine and Erbitux® to R0 or R1 Resected Pancreatic CancerAdenocarcinomaNCT00395252Carmen Schade-Brittinger76
已完成
2 期
Study Assessing Immunogenicity and Safety of IC43 In Intensive Care PatientsPneumonia, Ventilator-AssociatedNCT00876252Valneva Austria GmbH400
已完成
2 期
Multi Immunotherapy to Test Tolerance and XolairFood AllergyNCT02626611Kari Christine Nadeau70
已完成
2 期
Trial of a Chikungunya Vaccine, PXVX0317 CHIKV-VLP, in Healthy AdultsChikungunya Virus InfectionNCT03483961Bavarian Nordic445