A Study of JMT101 in Patients With Metastatic Colorectal Cancer

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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer (mCRC)
• Intervention / Treatment: Drug: JMT101; Drug: SG001; Drug: Irinotecan; Drug: Regorafenib (Stivarga)

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ranged from 18 to 75 years old (inclusive), regardless of gender;
2. Pathological diagnosis as metastatic colorectal adenocarcinoma, with RAS and BRAF wild-type and non-dMMR/MSI-H;
3. Tumor tissue available for central laboratory testing;
4. 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;
5. Measurable disease according to RECIST1.1;
6. Eastern Cooperative Oncology Group (ECOG) score 0-1 points;
7. Life expectancy ≥3 months
8. Adequate main organs and bone marrow function.
9. Patients must give informed consent to this study before the experiment and voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Previously used anti PD-1, anti PD-L1, anti CTLA-4, or cellular immunotherapy;
2. Central nervous system metastasis or meningeal metastasis;
3. Patients with high risk of bleeding due to tumor invasion of important arteries;
4. Uncontrolled or requiring repeated drainage of pleural effusion, pericardial effusion, or abdominal effusion;
5. Patients who require continuous use of morphine-based drugs to control pain;
6. The adverse reactions of previous anti-tumor treatments (including radiotherapy) have not yet recovered to CTCAE 5.0 evaluation ≤ level 1;
7. Diagnosed as a second primary malignant tumor within 5 years prior to the first administration of the study drug;
8. 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;
9. 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;
10. Use of immunosuppressive medications within 14 days prior to the first dose of study drug;
11. 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;
12. Have received radiation therapy or other localized palliative treatment within 14 days before the first dose of study drug;
13. Have undergone major surgery (excluding needle biopsy) or suffered severe traumatic injury within 28 days before the first dose of study drug;
14. Have a history of serious cardiovascular disease;
15. Previous or current presence of interstitial pneumonia/lung disease;
16. History of autoimmune diseases;
17. A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation;
18. Have infectious diseases requiring systemic anti-infective treatment;
19. Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis;
20. Known presence of hypersensitivity or intolerance to any component of EGFR monoclonal antibody, PD-1 monoclonal antibody, irinotecan hydrochloride injection, regorafenib and its excipients;
21. Women during lactation or pregnancy; women with fertility tested positive for blood pregnancy within 7 days prior to enrollment in the trial;
22. 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;
23. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 13, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: JMT101-011

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