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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LPM6690176 24 mg/m2 | Experimental | LPM6690176 capsules administered 24 mg/m2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI+Bevacizumab |
|
| LPM6690176 36 mg/m2 | Experimental | LPM6690176 capsules administered 36 mg/m2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI+Bevacizumab |
|
| LPM6690176 42 mg/m2 | Experimental | LPM6690176 capsules administered 42 mg/m2 orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFIRI+Bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LPM6690176 | Drug | LPM6690176 orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib: Dose-limiting toxicities (DLTs) | From the first dose of study drug treatment through Cycle 1 (28 days) | |
| Phase Ib: Maximum tolerated dose (MTD) | From the first dose of study drug treatment through Cycle 1 (28 days) | |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Overall response rate (ORR) | Approximately 2 years | |
| Duration of response (DOR) | Approximately 2 years | |
| Disease control rate (DCR) |
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Inclusion Criteria:
(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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lin Shen, Doctor | Contact | 0086-10-88196561 | doctorshenlin@sina.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | China |
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| Bevacizumab | Biological | Bevacizumab intravenously |
|
| FOLFIRI (5-Fluorouracil, Folinic acid, Irinotecan) | Drug | FOLFIRI intravenously |
|
| 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) |
| 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) |
| 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 |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D005472 | Fluorouracil |
| D002955 | Leucovorin |
| D000077146 | Irinotecan |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
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