Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply.

5.1.1. Part A and B

Age

1. Are an acceptable age to provide informed consent according to local regulations and are

at least 18 years of age.

Type of participant and disease characteristics

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 × 109

/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 × 109

/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 ≤2.5 × ULN

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TBL <1.5 × ULN OR direct bilirubin within normal limits for participants

with total bilirubin levels >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

≤1.5 × ULN

OR

≥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.

Previous treatment

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.

Other inclusion criteria

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 child[1]bearing 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.

5.1.2. Part A Only: Stage II-IIIB Disease, Resectable

Type of participant and disease characteristics

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 eligible.

b. Pathologic Stage II-IIIB (N2) NSCLC treated with initial upfront resection.

13. Had curative intent resection defined as lobectomy, sleeve lobectomy, bilobectomy, or

pneumonectomy. En bloc resection, for example, chest wall resection, or sub-anatomic

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resection, such as wedge resection or segmentectomy, is only permitted if performed in

addition to any of the previously listed curative intent resections.

a. Must undergo complete resection, defined as pathologic microscopic margin free

of invasive carcinoma at the parenchyma, bronchus, and vascular margins.

Carcinoma in situ can be present at bronchial margin.

b. A systematic complete mediastinal lymph node dissection or a lobe-specific

mediastinal lymph node dissection is recommended (See Section 10.7). It is

recommended that normal appearing lymph nodes, if present, be biopsied or

removed.

14. Have no evidence of disease recurrence at clinical examination and baseline radiological

assessment as documented by contrast enhanced chest/upper abdomen CT scan, brain

CT/MRI and clinical examination within 28 days before the first dose of study

intervention.

Previous treatment

15. Prior treatment with chemotherapy required. Prior treatment with immune checkpoint

inhibitor allowed but must be in combination with chemotherapy in the neoadjuvant

setting.

a. Patients treated with presurgical therapy must receive platinum-based

chemotherapy with an immune checkpoint inhibitor before randomization.

b. Patients treated initially with surgery must receive adjuvant platinum-based

chemotherapy before randomization. These patients must begin adjuvant

chemotherapy within 12 weeks of their surgery date. These patients must also be

eligible to receive their first dose in this study at least 3 weeks but no more than 12

weeks from the last dose of adjuvant chemotherapy (Day 1 of last cycle).

5.1.3. Part B Only: Stage III Disease, Unresectable

Type of participant and disease characteristics

16. Have clinical Stage III, unresectable NSCLC, without progression on concurrent

platinum-based chemoradiotherapy. Staging is per AJCC 9th edition (Rami-Porta et al.

2024).

Previous treatment

17. Have received at least 50% of planned platinum-based chemotherapy concurrent with

radiation therapy, which must be completed within 1 to 42 days prior to randomization.

18. The final chemotherapy cycle must end prior to, or concurrently with, the final dose of

radiation.

19. Have received a total dose of radiation of at least 54 Gy as part of the chemoradiotherapy

prior to randomization.

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5.2. Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

5.2.1. Part A and B

Medical conditions

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 (<5mm), in situ

carcinoma, low grade carcinoid tumorlets are not an exclusion

d. recurrent NSCLC

21. Have a known EGFR mutation or ALK rearrangement.

22. 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

? non-melanomatous 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.

23. Have current or a history of non-infectious pneumonitis or interstitial lung disease that

requires steroids.

24. Have an active uncontrolled infection requiring systemic therapy.

25. Had an allogenic tissue or solid organ transplant.

26. 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.

27. 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.

28. Have active or prior documented inflammatory bowel disease, such as Crohn’s disease or

ulcerative colitis.

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29. 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.

30. 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.

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 mental health disorder, severe dyspnea at rest or requiring oxygen

therapy. Screening for chronic conditions is not required.

36. Have an active malabsorption syndrome or other condition likely to affect gastrointestinal

absorption of the study intervention.

Prior and concomitant therapy

37. 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.

38. Have any other unresolved Grade >2 toxicities, except for alopecia, from prior therapy.

39. 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

40. 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.

41. 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.

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Other exclusion criteria

42. Are pregnant, breastfeeding, or plan on becoming pregnant or breastfeeding during the

study or within 180 days after the last dose of study intervention.

5.2.2. Part A Only

Prior and concomitant therapy

43. For patients treated with upfront surgical resection, have received more than 4 cycles of

adjuvant chemotherapy

44. For patients treated with presurgical chemo-immunotherapy, have received any adjuvant

therapy

5.2.3. Part B Only

Prior and concomitant therapy

45. Have received non-standard of care treatment regimens, such as induction chemotherapy

plus immunotherapy followed by concurrent chemoradiation therapy.

46. Have received sequential chemotherapy followed by radiation therapy

47. Have Grade ≥ 2 pneumonitis from prior chemoradiation therapy