Adjuvant Therapy with RO7435846 (divarasib) versus Pembrolizumab or Nivolumab or Observation in Patients After Surgery for Stage II‑III KRAS G12C NSCLC

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What is this study about?

The study focuses on patients who have had surgery to remove Non-Small Cell Lung Cancer that was at stage II or III and carries the KRAS G12C mutation, a change in a gene that can help the cancer grow. After surgery, the disease can return, so the trial is testing an oral medication called RO7435846 (divarasib) and comparing it with two already‑approved immunotherapy drugs, pembrolizumab and nivolumab, or with simply watching the patient without further treatment (observation). Immunotherapy is a type of medicine that helps the body’s own immune system fight cancer.

The purpose of the study is to compare how well the new drug works against standard immunotherapy or observation in preventing cancer from coming back. Participants will be randomly placed into one of the three groups, receive the assigned treatment (a daily tablet for the new drug or an intravenous infusion for the immunotherapies), and then be monitored with regular doctor visits and imaging scans to check for any signs of the disease returning or new health issues over several years.

1 enrollment and consent

after joining the study you sign an informed consent form that explains the purpose of the trial and what will be required of you.

2 randomization

the study team assigns you randomly to one of the following groups: divarasib tablets, pembrolizumab intravenous infusion, nivolumab intravenous or subcutaneous injection, or observation without study medication.

3 baseline assessments

before any treatment begins you undergo medical history review, physical examination, laboratory tests, and imaging scans to document the current status of your cancer.

4 start of assigned therapy

if you are assigned to divarasib, you take an oral film‑coated tablet as directed by the study protocol. the exact dose and schedule are defined by the investigators.

if you are assigned to pembrolizumab, you receive an intravenous infusion at the clinic according to the schedule set by the study protocol.

if you are assigned to nivolumab, you receive either an intravenous infusion or a subcutaneous injection as directed by the study protocol.

if you are assigned to observation, you do not receive any study medication but you attend regular clinic visits for monitoring.

5 regular clinic visits and safety monitoring

you return to the clinic at intervals specified in the protocol to receive your medication (or to have a check‑up if you are in the observation group). during each visit the study staff checks for side effects, records any adverse events, and may perform laboratory tests.

6 periodic disease evaluation

at scheduled times you undergo imaging scans and clinical examinations to assess whether the cancer has returned. this evaluation contributes to the measurement of disease‑free survival (the time from randomization until cancer recurrence or death).

7 continuation of therapy

you continue taking the assigned medication or attending observation visits until one of the following occurs: the cancer returns, side effects become unacceptable, or the study reaches its planned end date.

8 final follow‑up and study completion

after treatment stops, you have a final follow‑up visit where overall survival (the time from randomization until death from any cause) and long‑term safety are recorded. the study then closes for your participation.

Who Can Join the Study?

KRAS G12C mutation must be confirmed in your tumor tissue. This is a specific genetic change that can affect how the cancer behaves.
Your overall health must be rated as ECOG Performance Status 0 or 1. This means you are fully active (0) or able to carry out light work (1) without being bedridden.
You need a diagnosis of stage II to stage IIIB non‑small cell lung cancer (NSCLC) based on a tissue or cell test (histology or cytology) and it can be either squamous or non‑squamous type.
You must have had a complete surgical removal (resection) of the lung cancer, meaning all visible tumor was taken out.
You must have previously received neoadjuvant immune checkpoint inhibitor therapy (such as pembrolizumab or nivolumab) together with a platinum‑based doublet chemotherapy regimen. “Neoadjuvant” means the treatment was given before surgery, and “immune checkpoint inhibitor” is a drug that helps your immune system attack cancer.
There must be no signs of cancer returning or spreading (no recurrence or metastatic disease) at the time of enrollment.

Who Cannot Join the Study?

Having taken a KRAS inhibitor (a drug that blocks a specific gene change) or any other anti‑cancer therapy not listed in the study plan before joining the trial.
Having received radiation therapy for NSCLC (non‑small cell lung cancer), except for a small, symptom‑focused radiation given before the tumor‑removing surgery (localized symptom‑directed radiation prior to surgical resection).
If the cancer disappears completely after treatment given before surgery (pCR – pathologic complete response after neoadjuvant treatment).
If you have had a severe immune‑related side effect (Grade 3 or higher) that is still resolved, or a moderate or worse immune‑related side effect (Grade 2 or higher) that has not resolved, from the treatment given before surgery (neoadjuvant immunotherapy).
If you received a live, attenuated vaccine (a vaccine with a weakened form of the germ) within 4 weeks before being placed into a study group (randomization), or if you might need such a vaccine while on the study drug or within 5 months after the last dose of the study drug.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Azienda Ospedaliero Universitaria Careggi	Florence	Italy

Other Sites

Site Name	City	Country
Saarland University Hospital	Homburg	Germany
Klinikum Esslingen GmbH	Esslingen Am Neckar	Germany
Barmherzige Brueder gemeinnuetzige Krankenhaus GmbH	Regensburg	Germany
Ospedale San Raffaele S.r.l.	Milan	Italy
Azienda Ospedaliero Universitaria Di Modena	Modena	Italy
Ospedale P. Pederzoli Casa Di Cura Privata S.p.A.	Peschiera Del Garda	Italy
CHU Helora	La Louviere	Belgium
Uuqtqqtihlygbncefowpk Ewymc Aun	Essen	Germany
Kdvurfzk Dxl Lkupcrtxfcznawcb Sjwtypmzp gtsvw	Stuttgart	Germany
Sfft Klfeoubn Oyraairbg Gdac	Offenbach Am Main	Germany
Ktpymkjm Wjevuhtlt Mwmwe gtsnp	Wuerzburg	Germany
Eceqocumrgwyf Kfiwhfpe Bahyjl gbulh	Bielefeld	Germany
Vrwumkdx Nlanulro fhtf Gkwlefqyuk Gvcn	Berlin	Germany
Aoohckulg Kfoeii Gkrqkrp Gkso	Gauting	Germany
Pnrmmzezfyszx Oknkvilwp	Oldenburg In Holstein	Germany
Lvtjv Gdtvhtn Hhvhuklh Oj Avkoax	Athens	Greece
Amyfmj Mmuwchk Ckauap Sdvr	Thessaloniki	Greece
Gtqwbcb Uewedvryfo Hixrriom Ow Lozghrf	Larissa	Greece
Hefma Dmagad Hodvzylu Cusixm	Athens	Greece
Udeumuephv Gyizcbu Hnatbhyc Abbaxpd Gjvgewa Hvodroay Oh Wkur Ahbiwg H Auhb Vzwxivb	Chaidari	Greece
Swd Lkjoiwpvnngl Hmxqtxvs Swrf	Thessaloniki	Greece
Amerpkx Odlnbcwxgbj Ulcrykxwdqbir Cupnbuiiznnl Dneej Snpmsh E Dqtds Sfwjaeb Dr Tlkgqm	Turin	Italy
Hujmdokl Seqyg Mxsfz Dbqct Msxmypftzaqk	Perugia	Italy
Cshigfxl Gfxzciytc Sevkms	Bergamo	Italy
Fwsudhwsok Ixili Skg Ggubbnj Ded Tymyalk	Monza	Italy
Fzolnvumye Iydmutiaak Isggfrup Nsojknugzqb Bgylr	Milan	Italy
Irqoou Iujubyfa Fqsbxyxvbiffz Opymucjpmyx	Rome	Italy
Ugfiyhtdkj Ou Asznots	Edegem	Belgium
Jikdd Zokyehdwyg	Hasselt	Belgium
Ctnpdz hyfpswtizfn uswcqrcotbiop dl Ldsni	Liege	Belgium

Trial status

Country	Status	Recruitment Start
Belgium	Not yet recruiting	01.09.2026
Germany	Not yet recruiting	01.09.2026
Greece	Not yet recruiting	01.09.2026
Italy	Not yet recruiting	01.09.2026

Trial locations

Investigated Drugs:

Divarasib is an oral medication taken as a film‑coated tablet. In this study it is the new drug being tested to see if it can keep cancer from coming back after surgery. It works by blocking a specific protein that helps cancer cells grow, so researchers hope it will improve the time patients stay free of disease.

Pembrolizumab is an immunotherapy given by injection (either into a vein or under the skin). It helps the body’s immune system recognize and attack cancer cells. In the trial it is one of the standard treatments that the new drug is compared against.

Nivolumab is another immunotherapy given by injection. Like pembrolizumab, it boosts the immune system’s ability to find and destroy cancer cells. It is also used as a comparator to see how well the new drug works.

Observation means that patients do not receive any additional medication after surgery. Instead, they are closely monitored with regular check‑ups and tests to see if the cancer returns. This approach is included in the study as a reference point for how patients do without further treatment.

Resected stage II–III KRAS G12C‑positive non‑small cell lung cancer – This disease is a form of lung cancer that begins in the cells lining the airways and is classified as non‑small cell type. It carries a specific KRAS G12C genetic alteration that can influence how the cancer cells grow. Patients have undergone surgical removal of the tumor and are classified as stage II or III, indicating spread to nearby lymph nodes or structures. After surgery, any remaining cancer cells may slowly increase in number and can reappear at the original site or in other parts of the body. The disease can progress from local recurrence to involvement of distant organs over time.

Trial ID:

2025-524263-21-01

Protocol code:

BO45885

Trial Phase:

Therapeutic confirmatory (Phase III)

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Adjuvant Therapy with RO7435846 (divarasib) versus Pembrolizumab or Nivolumab or Observation in Patients After Surgery for Stage II‑III KRAS G12C NSCLC

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?