NSCLC
Conditions
Interventions
Experimental group-A:Olomorasib in combination with pembrolizumab
Control group-A:Placebo with pembrolizumab
Experimental Group-B:Olomorasib in combination with durvalumab
Control group-B:Placebo with durvalumab
Sponsors
Jilin Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Part A:1. Are an acceptable age to provide informed consent according to local regulations and are at least 18 years of age. 2. Have histological or cytological confirmation of NSCLC. 3. Have evidence of KRAS G12C mutation in samples from tumor or blood, as determined by molecular testing performed in a CLIA, ISO/IEC, CAP, or similarly certified laboratory per local guidelines, including, but not limited to IVDR compliance, as applicable. 4. Have known PD-L1 expression (0% to 100%) of tumor cells as determined by an IHC assay performed in a CLIA, ISO/IEC, CAP, or similarly certified laboratory as per local guidelines, including, but not limited to IVDR compliance, as applicable. 5. Have an ECOG performance status of 0 or 1. 6. Have adequate organ and marrow function as defined in the table below. Note: Transfusions to increase a participant’s hemoglobin level or initiation of erythropoietin or G-CSF therapy to meet these criteria are not allowed in the 14 days before the first dose of study intervention. Test Result Hematology Absolute neutrophil count >=1.0 × 10^9/L (>=1.0 × 103/µL or >=1.0 GI/L) Must be met without G-CSF therapy within the last 14 days Platelet count >=75 × 10^9/L (>=75 × 103/µL or >=75 GI/L) Hemoglobin level >=8.0 g/dL or >= 5 mmol/L Must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 14 days Clinical chemistry ALT and AST 1.5 × ULN For patients with Gilbert’s syndrome, total bilirubin may be >1.5 × ULN, however direct bilirubin must be normal Renal Serum creatinine OR Measured creatinine clearance OR Calculated creatinine clearance or GFR or institutional standards =30 mL/min for participant with creatinine levels >1.5 × institutional ULN Note: Use Cockcroft-Gault CrCl formula to calculate creatinine clearance or institutional standards. Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; G-CSF = granulocyte-colony stimulating factor; GFR = glomerular filtration rate; TBL = total bilirubin level; ULN = upper limit of normal. 7. Have recovered from any previous surgical procedure before randomization. Contraceptive and barrier requirements; 8. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For the contraception requirements of this protocol, see Section 10.4. 9. Individuals assigned female at birth must have evidence of post-menopausal status, or individuals of child-bearing potential must have a negative pregnancy test (serum test is preferable) result at screening and have a negative serum or urine test result 72 hours before treatment with study intervention. See Section 10.4.1 for definitions of childbearing potential and menopausal status. 10. Are able to swallow oral medication. Informed consent; 11. Are capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 12. Have Stage II-IIIB (N2) NSCLC per AJCC 9th edition (Rami-Porta et al. 2024) including either: a. Clinical Stage II-IIIB (N2) treated with presurgical chemoimmunotherapy, with residual tumor present at time of surgery. Patients with a pathologic complete response are not el
Exclusion criteria
Exclusion criteria: 1.Prat A:20.Have 1 of these tumor types a.large cell neuro-endocrine cancer b.mixed small cell and non-small cell lung cancer c.2 synchronous primary invasive NSCLC in different ipsilateral or contralateral lobes. Note – Concurrent minimally invasive adenocarcinoma ( 1000 IU/mL •patients with positive HBsAg, or anti-HBc, or detectable HBV DNA, who are unable to undergo monitoring of HBsAg, HBV DNA, and liver tests (ALT, AST, ALP, TBL, GGT) at least every 3 months. 31.Have a current infection with HCV, defined as positive for HCV RNA. 32.Have a known history of active tuberculosis. 33.Have clinically significant active cardiovascular disease or history of myocardial infarction or unstable angina within 6 months prior to planned start of study. 34.Have a 12-lead ECG QT interval corrected for heart rate using Fridericia’s formula (QTcF) >470 msec. If QTcF >470 msec on 1 ECG is obtained during the screening, obtain 2 additional measurements and use the average of the 3 measurements to determine eligibility. Exception: Individuals with implanted pacemakers. 35.Have a serious preexisting medical condition that, in the judgment of the investigator, would preclude participation in this study, including but not limited to, substance use disorder, an unstable me
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| investigator assessed the patients' disease-free survival;PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| OS;HRQoL (Health-Related Quality of Life) Change from Baseline;Safety endpoints include TEAEs;Patient-reported tolerability;OS;HRQoL (Health-Related Quality of Life) Change from Baseline;Combination therapy period: every cycle. Monotherapy period: every cycle;Safety endpoints include TEAEs;Changes in NSCLC-related symptoms;Patient-reported tolerability; | — |
Countries
China
Contacts
Public Contactcheng ying
Jilin Cancer Hospital
Outcome results
None listed