Non-small cell lung cancer
Conditions
Interventions
Experimental Group - Part B:Olomorasib (an investigational KRAS G12C inhibitor) combined with durvalumab
Control Group - Part A:Combination therapy + monotherapy
Experimental Group - Part A:Olomorasib (an investigational KRAS G12C inhibitor) combined with pembrolizumab
Control Group - Part B:Placebo combined with durvalumab
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Part A and Part B: 1.According to local regulations, one has reached the acceptable age for providing informed consent and is at least 18 years old. Subject types and disease characteristics 2. Histological or cytological confirmed NSCLC. 3. Evidence of KRAS G12C mutations must be present in tumor or blood samples and determined by molecular testing in CLIA, ISO/IEC, CAP or other similar certified laboratories in accordance with local guidelines (including but not limited to IVDR compliance [if applicable]). 4. It must have known PD-L1 expression in tumor cells (0% to 100%), and be determined by IHC analysis in CLIA, ISO/IEC, CAP or other similar certified laboratories in accordance with local guidelines (including but not limited to IVDR compliance [if applicable]). 5. The ECOG physical status is either 0 or 1. 6. Have appropriate organ and bone marrow functions; 7. The patient must have fully recovered from any previous surgical operation before randomization. 8. The contraceptive methods used by the subjects should comply with the local regulations on contraceptive methods for clinical research subjects. 9. For subjects recorded as female at birth, there must be evidence of postmenopausal status, or for fertile subjects, the pregnancy test results at the time of screening must be negative (serum test preferred), and the serum or urine pregnancy test results within 72 hours prior to the start of the study treatment must be negative. 10. Be capable of swallowing oral medication. 11. Be able to provide the signed informed consent as described in Section 10.1.3, including compliance with the informed consent Form (ICF) and the requirements and restrictions listed in this study protocol. 12. According to AJCC 9th Edition, patients with stage II-IIIB (N2) NSCLC (Rami-Porta et al. 2024) Including: A. The patient has a clinical stage of II-IIIB (N2), has received preoperative chemoimmunotherapy, and there is residual swelling during the operation Tumor. Patients who have achieved pathological complete response are not eligible for inclusion. b. NSCLC with postoperative pathological stage II-IIIB (N2) that has received initial pre-resection treatment. 13. Having undergone radical resection, defined as lobectomy, sleeve lobectomy, bilateral lobectomy or pneumonectomy. Only whole resections (such as chest wall resections) or subanatomical resections (such as wedge resections or segmental resections) performed on the basis of any of the radical resections listed earlier are permitted. a. Complete resection must be performed, defined as the absence of invasive cancer in the parenchyma, bronchi and vascular margins under pathological microscopy. Carcinoma in situ can exist at the margins of the bronchi. b. It is recommended to perform a systematic and complete mediastinal lymph node dissection or a mediastinal lymph node dissection of the lung lobe. It is recommended to perform biopsy or resection on lymph nodes with normal appearance (if present). 14. Within 28 days prior to the first administration, no evidence of disease recurrence was found through enhanced chest/upper abdominal computed tomography (CT) scans, brain CT/ magnetic resonance imaging (MRI), and clinical examination records. Neither the clinical examination nor the baseline radiological assessment. 15. One must have received chemotherapy in the past. Previous treatment with immune checkpoint inhibitors is allowed, but it must be used in combination with chemotherapy during neoadjuv
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 nonsmall cell lung cancer c.2 synchronous primary invasive NSCLC in different ipsilateral or contralateral lobes. Note – Concurrent minimally invasive adenocarcinoma ( 1000 IU/mL; (3) 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. 12.Have a current infection with HCV, defined as positive for HCV RNA. 13.Have a known history of active tuberculosis. 14.Have clinically significant active cardiovascular disease or history of myocardial infarction or unstable angina within 6 months prior to planned start of study. 15.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. 16.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 mental health disorde
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: investigator assessed the patients' disease-free survival;Part B: BICR assessed progression free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: efficacy;Part A: HRQoL (Health-Related Quality of Life) Change from Baseline;Part A: Safety;Part A: Patient-reported tolerability;Part B: efficacy;Part B: Safety;Part B: Changes in patient-reported NSCLC-related symptoms;Part B: HRQoL (Health-Related Quality of Life) Change from Baseline;Part B: Patient-reported tolerability; | — |
Countries
China
Contacts
Public ContactZhong Wenzhao
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed