A Study of JMT101 in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This study is a phase Ⅱ, randomized, controlled, open-label, multi-center study with safety run-in to evaluate the efficacy and safety of JMT101 combined with Irinotecan and SG001 in Patients with Metastatic Colorectal Cancer (mCRC).

Official Title
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A Randomized, Controlled, Open-label Phase Ⅱ Study of The Safety, Tolerability and Efficacy of JMT101 and Irinotecan Combined With SG001 in Patients With Metastatic Colorectal Cancer (mCRC)

Conditions
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Metastatic Colorectal Cancer (mCRC)

Intervention / Treatment
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* Drug: JMT101
* Drug: SG001
* Drug: Irinotecan
* Drug: Regorafenib (Stivarga)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ranged from 18 to 75 years old (inclusive), regardless of gender; Pathological diagnosis as metastatic colorectal adenocarcinoma, with RAS and BRAF wild-type and non-dMMR/MSI-H; Tumor tissue available for central laboratory testing; Metastatic colorectal cancer with disease progression after 2nd line treatment; previously received standard chemotherapy based on fluorouracil, oxaliplatin, irinotecan; patients are allowed to previously receive EGFR and/or VEGF inhibitors, but not allowed to previously receive regorafenib, fruquintinib, or TAS-102; Measurable disease according to RECIST1.1; Eastern Cooperative Oncology Group (ECOG) score 0-1 points; Life expectancy ≥3 months Adequate main organs and bone marrow function. Patients must give informed consent to this study before the experiment and voluntarily sign a written informed consent form. Exclusion Criteria: Previously used anti PD-1, anti PD-L1, anti CTLA-4, or cellular immunotherapy; Central nervous system metastasis or meningeal metastasis; Patients with high risk of bleeding due to tumor invasion of important arteries; Uncontrolled or requiring repeated drainage of pleural effusion, pericardial effusion, or abdominal effusion; Patients who require continuous use of morphine-based drugs to control pain; The adverse reactions of previous anti-tumor treatments (including radiotherapy) have not yet recovered to CTCAE 5.0 evaluation ≤ level 1; Diagnosed as a second primary malignant tumor within 5 years prior to the first administration of the study drug; Have received anti-tumor treatments such as chemotherapy, biological therapy, targeted therapy, etc. within 21 days before the first dose of the study drug; radiotherapy within 2 weeks before the first dose of the study drug; Chinese medicine or Chinese patent medicine with anti-tumor effect within 1 week before the first dose of the study drug; Have received a live viral vaccine or live-attenuated vaccine within 28 days before the first dose of study drug or plan to receive it during the study; Use of immunosuppressive medications within 14 days prior to the first dose of study drug; Those who use strong CYP3A4 inducers within 14 days before the first administration of the study drug, or those who use strong CYP3A4 inhibitors or strong UGT1A1 inhibitors within 1 week, or those who cannot suspend the use of the above drugs during the study; Have received radiation therapy or other localized palliative treatment within 14 days before the first dose of study drug; Have undergone major surgery (excluding needle biopsy) or suffered severe traumatic injury within 28 days before the first dose of study drug; Have a history of serious cardiovascular disease; Previous or current presence of interstitial pneumonia/lung disease; History of autoimmune diseases; A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation; Have infectious diseases requiring systemic anti-infective treatment; Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis; Known presence of hypersensitivity or intolerance to any component of EGFR monoclonal antibody, PD-1 monoclonal antibody, irinotecan hydrochloride injection, regorafenib and its excipients; Women during lactation or pregnancy; women with fertility tested positive for blood pregnancy within 7 days prior to enrollment in the trial; Any male and female patients with fertility who refuse to use effective contraceptive methods throughout the entire trial period and within six months after the last administration; Other conditions that, in the opinion of the investigator, may affect the safety or compliance of drug treatment in this study, including but not limited to: psychiatric disorders, any severe or uncontrollable diseases, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JMT101+SG001+ Irinotecan<br> | Drug: JMT101<br>* JMT101, 6 mg/kg, IV infusion once every two weeks (one treatment cycle is 4 weeks).<br>Drug: SG001<br>* 240 mg, IV infusion once every two weeks (one treatment cycle is 4 weeks).<br>Drug: Irinotecan<br>* 180mg/m^2, IV infusion once every two weeks (one treatment cycle is 4 weeks).<br>|
| Experimental: JMT101+Irinotecan<br> | Drug: JMT101<br>* JMT101, 6 mg/kg, IV infusion once every two weeks (one treatment cycle is 4 weeks).<br>Drug: Irinotecan<br>* 180mg/m^2, IV infusion once every two weeks (one treatment cycle is 4 weeks).<br>|
| Active Comparator: Regorafenib (Stivarga)<br> | Drug: Regorafenib (Stivarga)<br>* 160 mg, taken orally once daily for the first 21 days of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) |  | After1 cycle of treatment of the safety run-in phase patients (each cycle is 28 days) | 
| Overall response rate (ORR) |  | Up to approximately 2 years | 
| Incidence and severity of adverse events (AE) and serious adverse events (SAE) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. | Up to approximately 2 years | 
| Disease Control Rate (DCR) | Determined using RECIST v1.1 criteria. | Up to approximately 2 years | 
| Overall Survival (OS) | Duration from the date of initial treatment to the date of death due to any cause. | Up to approximately 2 years |