Prospective registration

A Phase 3, Multicenter, Double-Blind, Placebo-controlled Study Assessing the Efficacy and Safety of Olomorasib in Combination with Standard of Care Immunotherapy in Participants with Resected or Unresectable KRAS G12C-Mutant, Non-Small Cell Lung Cancer - SUNRAY-02

A Phase 3, Multicenter, Double-Blind, Placebo-controlled Study Assessing the Efficacy and Safety of Olomorasib in Combination with Standard of Care Immunotherapy in Participants with Resected or Unresectable KRAS G12C-Mutant, Non-Small Cell Lung Cancer - SUNRAY-02

Ye Shenru 

Zhong Wenzhao 

44th Floor, Zhujiang International Building, Yuehua Road, Yuexiu District, Guangzhou City, Guangdong Province

No. 106, Zhongshan 2nd Road, Guangzhou City, Guangdong Province

Aikunwei Pharmaceutical Technology (Shanghai) Co., LTD

Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)

Yes

Ethics Review Committee of Guangdong Provincial People's Hospital

Bai Sheng

No. 106, Zhongshan 2nd Road, Guangzhou City, Guangdong Province

Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)

No. 106, Zhongshan 2nd Road, Guangzhou City, Guangdong Province

Eli Lilly Suzhou Pharmaceutical Co., LTD

Non-small cell lung cancer

Interventional study

3

Parallel 

Part A: To compare the efficacy of olomorasib in combination with pembrolizumab versus placebo with pembrolizumab Part B: To compare the efficacy of olomorasib in combination with durvalumab versus placebo with durvalumab

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 neoadjuvant therapy. Patients undergoing preoperative treatment must receive immune checkpoint inhibitor therapy and platinum-based chemotherapy before randomization. Patients who initially underwent surgical treatment must receive platinum-based chemotherapy as adjuvant therapy before randomization. These patients must start adjuvant chemotherapy within 12 weeks after the date of surgery. These patients must also receive the first dose of this study at least 3 weeks but no more than 12 weeks after the last dose of adjuvant chemotherapy (the first day of the last cycle). Only Part B: Unresectable stage III NSCLC 16. NSCLC with clinical stage III, unresectable, and no disease progression after platinum-based concurrent chemoradiotherapy. 17. At least 50% of the planned platinum-based concurrent chemoradiotherapy must be received, and it must be completed within 1 to 42 days before randomization. 18. The last chemotherapy cycle must be completed before or simultaneously with the last radiotherapy. Before randomization, as part of chemoradiotherapy, the subjects must receive a total radiotherapy dose of at least 54 Gy.

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 (<5mm), in situ carcinoma, low grade carcinoid tumorlets are not an exclusion recurrent NSCLC; 2.Have a known EGFR mutation or ALK rearrangement; 3.Have a known malignancy that is progressing or required active treatment within the past 3 years before screening. Exceptions: These conditions are allowed, if already successfully treated ?nonmelanomatous skin cancer ?carcinoma in situ of the cervix ?ductal carcinoma in situ of the breast ?high grade prostatic intraepithelial neoplasia (Gleason score 6/ Grade Group 1) ?non-muscle-invasive bladder cancer, not associated with high risk for progression, or ?have received or are receiving adjuvant hormone therapy for breast or prostate cancer with no evidence of disease. 4.Have current or a history of non-infectious pneumonitis or interstitial lung disease that requires steroids. 5.Have an active uncontrolled infection requiring systemic therapy. 6.Had an allogenic tissue or solid organ transplant. 7.Have an active autoimmune disease that required systemic treatment in the past 2 years. Examples of systemic treatment includes the use of disease modifying agents, corticosteroids, or immunosuppressive drugs. Exception: Endocrine replacement therapy is allowed. Examples include thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency. 8.Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy (dose more than 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to first dose of study intervention Exception: corticosteroid premedication for contrast allergy is allowed. 9.Have active or prior documented inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. 10.Have a known history of HIV infection (HIV-1 or HIV-2 antibody positive). HIV testing is not required unless required by local health authorities. 11.Have a history of or current infection with HBV under one of the following conditions ?? patients with positive HBsAg or detectable HBV DNA who are not receiving HBV prophylaxis with a NA initiated at least 7 days prior to first dose of study intervention ?patients with HBV DNA > 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. 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 disorder, severe dyspnea at rest or requiring oxygen therapy. Screening for chronic conditions is not required. 17.Have an active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study intervention. 18.Have experienced any Grade ≥3 immune-related AE (irAE) or Grade ≥3 hypersensitivity while receiving any previous immunotherapy agent, or any unresolved irAE Grade >1. Exception: Endocrinopathies on replacement hormonal therapy. 19.Have any other unresolved Grade >2 toxicities, except for alopecia, from prior therapy. 20.Received a live vaccine or live attenuated vaccines within 30 days before the first dose of study; 21.Are currently enrolled in any other clinical study involving an investigational product within 4 weeks prior to the first dose of study intervention. In the case of monoclonal antibodies, 6 weeks prior to the first dose of study intervention. 22.Are currently enrolled in any type of medical research judged not to be scientifically or medically compatible with this study as determined by sponsor consult. 23.Are pregnant, breastfeeding, or plan on becoming pregnant or breastfeeding during the study or within 180 days after the last dose of study intervention. 24.For patients treated with upfront surgical resection, have received more than 4 cycles of adjuvant chemotherapy; 25.For patients treated with presurgical chemo-immunotherapy, have received any adjuvant therapy; 26.Part B: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 (<5mm), in situ carcinoma, low grade carcinoid tumorlets are not an exclusion d. recurrent NSCLC; 27.Have a known EGFR mutation or ALK rearrangement. 28.Have a known malignancy that is progressing or required active treatment within the past 3 years before screening. Exceptions: These conditions are allowed, if already successfully treated ? nonmelanomatous skin cancer ? carcinoma in situ of the cervix ? ductal carcinoma in situ of the breast ? high grade prostatic intraepithelial neoplasia (Gleason score 6/ Grade Group 1) ? non-muscle-invasive bladder cancer, not associated with high risk for progression, or ? have received or are receiving adjuvant hormone therapy for breast or prostate cancer with no evidence of disease. 29.Have current or a history of non-infectious pneumonitis or interstitial lung disease that requires steroids. 30.Have an active uncontrolled infection requiring systemic therapy. 31.Had an allogenic tissue or solid organ transplant. 32.Have an active autoimmune disease that required systemic treatment in the past 2 years. Examples of systemic treatment includes the use of disease modifying agents, corticosteroids, or immunosuppressive drugs. Exception: Endocrine replacement therapy is allowed. Examples include thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency. 33.Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy (dose more than 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to first dose of study intervention Exception: corticosteroid premedication for contrast allergy is allowed. 34.Have active or prior documented inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis. 35.Have a known history of HIV infection (HIV-1 or HIV-2 antibody positive). HIV testing is not required unless required by local health authorities. 36.Have a history of or current infection with HBV under one of the following conditions ? patients with positive HBsAg or detectable HBV DNA who are not receiving HBV prophylaxis with a NA initiated at least 7 days prior to first dose of study intervention ? patients with HBV DNA > 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. 37.Have a current infection with HCV, defined as positive for HCV RNA. 38.Have a known history of active tuberculosis; 39.Have clinically significant active cardiovascular disease or history of myocardial infarction or unstable angina within 6 months prior to planned start of study. 40.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. 41.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 disorder, severe dyspnea at rest or requiring oxygen therapy. Screening for chronic conditions is not required. 42.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 disorder, severe dyspnea at rest or requiring oxygen therapy. Screening for chronic conditions is not required. 43.Have experienced any Grade ≥3 immune-related AE (irAE) or Grade ≥3 hypersensitivity while receiving any previous immunotherapy agent, or any unresolved irAE Grade >1. Exception: Endocrinopathies on replacement hormonal therapy. 44.Have any other unresolved Grade >2 toxicities, except for alopecia, from prior therapy. 45.Received a live vaccine or live attenuated vaccines within 30 days before the first dose of study intervention. Exception: Seasonal influenza vaccines for injection, which are generally killed virus vaccines. Prior and concurrent clinical study experience; 46.Are currently enrolled in any other clinical study involving an investigational product within 4 weeks prior to the first dose of study intervention. In the case of monoclonal antibodies, 6 weeks prior to the first dose of study intervention. 47.Are currently enrolled in any type of medical research judged not to be scientifically or medically compatible with this study as determined by sponsor consult. Other exclusion criteria; 48.Are pregnant, breastfeeding, or plan on becoming pregnant or breastfeeding during the study or within 180 days after the last dose of study intervention. 49.Have received non-standard of care treatment regimens, such as induction chemotherapy plus immunotherapy followed by concurrent chemoradiation therapy. 50.Have received sequential chemotherapy followed by radiation therapy; 51.Have Grade >=2 pneumonitis from prior chemoradiation therapy;

Random sequences are randomly generated by the site authorized staff using the IWRS system. All participants will be centrally assigned to study intervention using an IWRS.

Double blind, blinded to study participants and investigators

None

CRF data will be collected using EDC in this study. Data entered into the EDC system provided by the Sponsor by the investigator or designee will be retained by the investigator as a separate copy as a source document. It is the responsibility of the investigator to identify any data that is considered source data and to confirm that the reported data is accurate and complete by signing the CRF. The test taker uses an electronic handheld device to record the PRO directly. The ePRO data will be used as source files and the investigator will not keep a separate written or electronic record of these data. Data collected through the data acquisition system provided by the Sponsor will be stored in third parties. The investigator will have continuous access to the data for the duration of the study until the data acquisition system is discontinued. Prior to the discontinuation of the system, the investigator will receive or access an archived copy of the relevant data for retention. Data managed by the central provider, such as laboratory test data, will be stored electronically in the central provider's database system, and reports and electronic transmissions will be provided to the investigator for review and retention. Subsequently, the data is transferred from the central vendor to the sponsor data repository. The complaint form data submitted to the sponsor will be encoded and saved in the global product complaint management system