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| Name | Class |
|---|---|
| Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | INDUSTRY |
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This study is aimed to evaluate the efficacy and safety of the Garsorasib combination therapy in KRAS G12C mutant locally advanced and metastatic NSCLC
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort1: PD-L1≧1%, Garsorasib+Benmelstobart+Anlotinib | Experimental | Histologically confirmed KRAS G12C mutant and PD-L1≧1% local advanced or metastatic NSCLC, at least 1 measurable lesion (RECIST 1.1) ECOG 0-1, treatment naive patients, first step enroll 6-9 patients, 3+3 dose escalation study start with Garsorasib 400mg qd. Patients randomised to Cohort1 or Cohort2. Garsorasib RP2D QD D1-21, Benmelstobart 1200 mg IV D1, q21d, Anlotinib 8mg QD, D1-14,q21d. N1=20 participants. |
|
| Cohort2: PD-L1≧1%, Benmelstobart+Anlotinib | Experimental | Histologically confirmed KRAS G12C mutant and PD-L1≧1% local advanced or metastatic NSCLC, at least 1 measurable lesion (RECIST 1.1) ECOG 0-1, treatment naive patients. |
|
| Cohort3: PD-L1<1%, Garsorasib+Cetuximab Beta Injection | Experimental | Histologically confirmed KRAS G12C mutant and PD-L1<1% local advanced or metastatic NSCLC, at least 1 measurable lesion (RECIST 1.1) ECOG 0-1, treatment naive patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Garsorasib, Benmelstobart, Anlotinib | Drug | Cohort1: Garsorasib RP2D QD D1-21, Benmelstobart 1200 mg IV D1, q21d, Anlotinib 8mg QD, D1-14,q21d. N1=20 participants. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) | Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR). | up to 180 days |
| DoR | DoR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. | up to 180 days |
| Measure | Description | Time Frame |
|---|---|---|
| PFS | defined as the time from randomization until the first documented progressive disease (PD) or death from any cause. | up to 180 days |
| DCR | Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease(SD). |
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Inclusion Criteria:
1. A written informed consent form should be signed prior to any study-related procedures 2. Male or female, aged 18 or above. 3.Histologically confirmed IIIB-IV NSCLC. 4.Subjects have not received systemic treatment for locally advanced or metastatic non-small cell lung cancer. 5.The patients should be confirmed with KRAS G12C mutation and provide PD-L1 test result. 6.At least 1 measurable lesion (RECIST 1.1 criteria). 7.ECOG 0-1. 8. Good organ function includes:
Neutrophil count≥1.5×109/L,
Platelet count≥90×109/L,
Hemoglobin≥90g/L
Serum creatinine≤1.5×upper limit of normal (ULN), creatinine clearance≥50 mL/min (Cockcroft-Gault formula)
Total bilirubin≤1.5×ULN
AST and ALT≤2.5×ULN; for patients with liver metastasis, AST and ALT≤5×ULN, the investigator should determine whether they are enrolled
Normal coagulation function: INR and PT≤1.5×ULN ,APTT≤1.5×ULN
Urinary protein in routine urinalysis is less than 2+, or 24-hour urinary protein quantification is < 1 g.
9. Life expectancy is at least 3 months; 10.Negative pregnancy test at enrollment. Male or female subjects should commit to take adequate and effective contraceptive measures or abstain from sexual for the duration of study participation and within 3 months after the last dose of the study drug
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Li Zhang, Doctor | Contact | +8613902282893 | zhangli@sysucc.org.cn | |
| Wenfeng Fang, Doctor | Contact | +8615322302066, | +8602087343822 | fangwf@sysucc.org.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University | Guangzhou | Guangdong | 510000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36546659 | Result | Yaeger R, Weiss J, Pelster MS, Spira AI, Barve M, Ou SI, Leal TA, Bekaii-Saab TS, Paweletz CP, Heavey GA, Christensen JG, Velastegui K, Kheoh T, Der-Torossian H, Klempner SJ. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. doi: 10.1056/NEJMoa2212419. Epub 2022 Dec 21. | |
| 34776511 |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| C000625192 | anlotinib |
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| Benmelstobart, Anlotinib | Drug | Benmelstobart 1200 mg IV D1, q21d, Anlotinib 8mg QD, D1-14,q21d. N2=20 participants. |
|
| Garsorasib, Cetuximab Beta Injection | Drug | Garsorasib 600mg BID, D1, q14d, Cetuximab Beta Injection 500mg/㎡ IV, q14d. N3=20 participants |
|
| up to 180 days |
| TTR | TTR was defined as Time from Randomization to First Response According to RECIST 1.1 Criteria | up to 180 days. |
| OS | OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. | up to 360 days. |
| Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021 Nov 15;6(1):386. doi: 10.1038/s41392-021-00780-4. |
| 38471457 | Result | Molina-Arcas M, Downward J. Exploiting the therapeutic implications of KRAS inhibition on tumor immunity. Cancer Cell. 2024 Mar 11;42(3):338-357. doi: 10.1016/j.ccell.2024.02.012. |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |