Metastatic Colorectal Cancer (mCRC)
Conditions
Brief summary
This study is consist of phase 1b (dose escalation + safety run-in) and phase 2 (randomized, controlled). Phase 1b is planned to evaluate the safety and tolerability of LPM6690176 capsule in combination with chemotherapy and Bevacizumab in patients with RAS mutant metastatic colorectal cancer (mCRC), to observe the dose-limiting toxicity (DLT), and to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D); Phase 2 is planned to preliminarily evaluate the efficacy of LPM6690176 capsule in combination with chemotherapy + Bev vs. chemotherapy + Bev in patients with previously untreated, RAS mutant mCRC.
Interventions
Sponsors
Luye Pharma Group Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Able to provide a signed informed consent; 2. Age ≥ 18 years and ≤ 75 years, both male and female; 3. Histologically confirmed metastatic colorectal cancer (CRC) with RAS mutation; 4. Prior therapies for colorectal cancer: (1 ) For phase 1b patients: who have failed or intolerable to prior first-line therapy; (2) For phase 2 patients: who have not received prior systemic therapy for metastatic colorectal cancer. 5\. At least one measurable lesion according to RECIST 1.1 criteria; 6. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; 7. Life expectancy≥ 6 months; 8. Adequate bone marrow and organ function; 9. Negative pregnancy test for women of childbearing potential. patients of childbearing potential should take effective contraceptive measures during study drug treatment and until 6 months after initiation of investigational product.
Exclusion criteria
1. Patients with known microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) who are suitable for immune checkpoint inhibitor therapy as assessed by the investigator; 2. Malignant tumors other than mCRC within 5 years before signing the informed consent; 3. Patients who did not recover from the AE of previous anti-tumor treatment to ≤ Grade 1; 4. Patients with body cavity effusion requiring local treatment or poorly controlled effusion; 5. Symptomatic brain metastasis, history of spinal cord compression or meningeal metastasis; 6. Underwent other therapeutic surgery other than diagnosis, biopsy, drainage, or expected to require major surgery during the study, or had unhealed wound, ulcer or fracture. 7. Current or previous uncontrolled concomitant non-gastrointestinal disease including, but not limited to myocardial infarction, unstable angina, coronary artery/peripheral artery bypass grafting, heart failure, cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, serious arrhythmia, current uncontrolled hypertension, previous history of hypertensive crisis or hypertensive brain disease, tumor invasion into major blood vessels, interstitial lung disease, interstitial pneumonia, pulmonary interstitial fibrosis, reversible posterior leukoencephalopathy syndrome (RPLS), etc.; 8. Current or past presence of the gastrointestinal abnormalities, including but not limited to active peptic ulcer, clinically significant gastrointestinal abnormalities prior to informed consent, active colitis, long-term anticoagulant therapy, antiplatelet therapy, etc.; 9. Current or past significant risk of bleeding; 10. Use of prohibited medication or therapy within the specified time; 11. History of drug abuse or alcoholism; 12. Known hypersensitivity to any component of any investigational product; 13. Pregnant and lactating women; 14. Other conditions that may increase the risk of the study or interfere with study results, in the judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b: Recommended Phase 2 Dose (RP2D) | From the first dose of study drug treatment through Cycle 1 (28 days) |
| Phase 2: Overall response rate (ORR) | Approximately 2 years |
| Phase Ib: Maximum tolerated dose (MTD) | From the first dose of study drug treatment through Cycle 1 (28 days) |
| Phase Ib: Dose-limiting toxicities (DLTs) | From the first dose of study drug treatment through Cycle 1 (28 days) |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve (AUC) | From Pre-dose of Cycle 1 Day 1 and up to Cycle 1 Day 9 (Approximately 10 days, each cycle is 28 days) |
| Duration of response (DOR) | Approximately 2 years |
| Disease control rate (DCR) | Approximately 2 years |
| Progression-free survival (PFS) | Approximately 2 years |
| Overall survival (OS) | Approximately 2 years |
| Maximum plasma concentration (Cmax) | From Pre-dose of Cycle 1 Day 1 and up to Cycle 1 Day 9 (Approximately 10 days, each cycle is 28 days) |
| Time to maximum plasma concentration (Tmax) | From Pre-dose of Cycle 1 Day 1 and up to Cycle 1 Day 9 (Approximately 10 days, each cycle is 28 days) |
| Phase 1b: Overall response rate (ORR) | Approximately 2 years |
| Elimination half-life (t1/2) | From Pre-dose of Cycle 1 Day 1 and up to Cycle 1 Day 9 (Approximately 10 days, each cycle is 28 days) |
| Trough observed plasma concentration (Ctrough) | From Pre-dose of Cycle 1 Day 1 and up to Cycle 1 Day 19 (Approximately 20 days, each cycle is 28 days) |
| Adverse Events (AEs) | Approximately 2 years |
Countries
China
Contacts
CONTACTLin Shen, Doctor
Outcome results
None listed