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Divarasib

Phase 3

Non-Small Cell Lung Cancer | Small molecule | Oncology |Roche Holding AG|Last Updated: Aug 10, 2026

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials4
Total Enrollment1,658

FDA Designations

No designations recorded

Clinical trial landscape

Divarasib · 8 trials · 4 indications

Phase 3 3Phase 1 5
NCT07541170A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC)Non-small Cell Lung Cancer
RECRUITING400 Analytics
NCT06793215A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung CancerNon-Small Cell Lung Cancer
RECRUITING600 Analytics
NCT06497556A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung CancerNon-Small Cell Lung Cancer
ACTIVE NOT_RECRUITING338 Analytics
PHASE3RECRUITING
A Study to Evaluate the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Participants With Resected Stage II-III KRAS G12C-Positive Non-Small Cell Lung Cancer (NSCLC)
Non-small Cell Lung CancerUnlock trial analytics
PHASE3RECRUITING
A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
Non-Small Cell Lung CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer
Non-Small Cell Lung CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Disease-free Survival (DFS), as Determined by the Investigator
From randomization to disease recurrence or death from any cause (Up to approximately 5 years)
Progression-Free Survival (PFS)
Up to approximately 5 years

PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)

Overall Survival (OS)
Up to approximately 5 years

OS is defined as the time from randomization to death from any cause

Maximum Plasma Concentration (Cmax) of Divarasib
Day 1 of Period 1 and Day 8 of Period 2
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-inf) of Divarasib
Day 1 of Period 1 and Day 8 of Period 2
Area Under the Concentration-time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Divarasib
Day 1 of Period 1 and Day 8 of Period 2
Plasma Concentration of Divarasib
Day 1 to Day 7
Maximum Observed Concentration (Cmax) of Divarasib
Day 1 to Day 7
Maximum Observed Plasma Concentration (Cmax) of Digoxin and Rosuvastatin
Day 1 of Period 1 and Day 5 of Period 2
Area Under the Plasma Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Digoxin and Rosuvastatin
Day 1 of Period 1 and Day 5 of Period 2
Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Digoxin and Rosuvastatin
Day 1 of Period 1 and Day 5 of Period 2
Time to Cmax (Tmax) of Digoxin and Rosuvastatin
Day 1 of Period 1 and Day 5 of Period 2
Percentage of Participants with Adverse Events (AEs)
Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years)

Secondary Endpoints

Overall Survival (OS)
From date of randomization to death from any cause (up to approximately 8 years)
DFS Rates at 2 and 3 Years, as Assessed by the Investigator
At Year 2 and Year 3
Number of Participants With Adverse Events (AEs)
From randomization to 60 days after the end of study treatment (up to approximately 8 years)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
DivarasibEXPERIMENTALParticipants will receive divarasib, orally (PO), once daily (QD) for up to 52 cycles (1 cycle = 21 days).
Control: Pembrolizumab or Nivolumab or ObservationACTIVE_COMPARATORParticipants will receive either pembrolizumab, nivolumab, or undergo observation, depending on the treatment received prior to surgery. No study treatment will be given to participants who will undergo observation.
Divarasib + PembrolizumabEXPERIMENTALParticipants will receive divarasib orally, once daily (QD) and pembrolizumab via intravenous (IV) infusion every 3 weeks (Q3W)
Pembrolizumab + Pemetrexed + Carboplatin or CisplatinACTIVE_COMPARATORParticipants will receive pembrolizumab, pemetrexed and carboplatin or cisplatin via IV infusion Q3W
KRAS G12C inhibitorACTIVE_COMPARATORParticipants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
Treatment AEXPERIMENTALParticipants will receive a single oral dose of Divarasib on Day 1.
Treatment BEXPERIMENTALParticipants will receive Rifampin once daily (QD) on Days 1 to 7 and Days 9 to 13. Participants will receive Divarasib followed by Rifampin on Day 8.
Cohort 1EXPERIMENTALParticipants will receive a single oral dose of Divarasib on Day 1.
Cohort 2EXPERIMENTALParticipants will receive a single oral dose of Divarasib on Day 1.
Cohort 3EXPERIMENTALParticipants will receive a single oral dose of Divarasib on Day 1.
Cohort 4EXPERIMENTALParticipants will receive a single oral dose of Divarasib on Day 1.
Cohort A - Combination Dose Finding + Dose ExpansionEXPERIMENTALParticipants will be enrolled in different cohorts to receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W). During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.
Cohort B - Combination Dose Finding + Dose ExpansionEXPERIMENTALParticipants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.
Cohort C - Dose ExpansionEXPERIMENTALParticipants enrolled in this cohort will receive one dose level of divarasib QD.
Cohort D - Dose ExpansionEXPERIMENTALParticipants enrolled in this cohort will receive one dose level of divarasib QD.

Interventions

NameTypeDescription
DivarasibDRUGDivarasib will be administered orally as per the schedule specified in the respective arm.
PembrolizumabDRUGPembrolizumab will be administered as either a 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) or 395 mg subcutaneous (SC) injection Q3W, for up to 13 cycles (1 cycle = 21 days).
NivolumabDRUGNivolumab will be administered as either a 480 mg IV infusion, every 4 weeks (Q4W) or 1200 mg SC injection Q4W, for up to 13 cycles (1 cycle = 28 days).
PemetrexedDRUGPemetrexed will be administered via IV infusion Q3W
CarboplatinDRUGCarboplatin will be administered via IV infusion Q3W
CisplatinDRUGCisplatin will be administered via IV infusion Q3W
SotorasibDRUGSotorasib will be administered orally QD
AdagrasibDRUGAdagrasib will be administred orally BID
RifampinDRUGRifampin will be administered QD on Days 1 to 7 and Days 9 to 13 and as a single oral dose on Day 8 as specified for the respective period.
ItraconazoleDRUGItraconazole will be administered BID on Day 1 and QD from Day 2 to 13 and as specified for the respective period.
DigoxinDRUGDigoxin will be administered together with Rosuvastatin as a drug cocktail as specified for the respective period
RosuvastatinDRUGRosuvastatin will be administered together with Digoxin as a drug cocktail as specified for the respective period
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Histological or cytological diagnosis of clinical Stage II-IIIB NSCLC of either non-squamous or squamous histology * Participants must have had complete resection of NSCLC * Prior treatment with neoadjuva...

Countries:United StatesArgentinaAustraliaBelgiumBrazilCanadaChinaDenmarkFranceGermanyGreeceHong KongHungaryIrelandItalyJapanMexicoNetherlandsNew ZealandPolandPortugalSingaporeSouth AfricaSouth KoreaSpainSwitzerlandTaiwanUnited KingdomAustriaFinlandSwedenThailandIsrael
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Competitive Landscape -Non-Small Cell Lung Cancer 389 trials

Recent Changes (Last 90 Days)

LOWAug 11, 2026NCT05789082lastUpdatePostDate: changed
LOWAug 11, 2026NCT07541170Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 11, 2026NCT05789082lastUpdatePostDate: changed
LOWAug 11, 2026NCT07541170Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 11, 2026NCT05789082lastUpdatePostDate: changed
LOWAug 11, 2026NCT07541170Status: NOT_YET_RECRUITING → RECRUITING
LOWAug 6, 2026NCT06793215lastUpdatePostDate: changed
LOWAug 6, 2026NCT06793215lastUpdatePostDate: changed
LOWAug 1, 2026NCT06793215lastUpdatePostDate: changed
LOWAug 1, 2026NCT06793215lastUpdatePostDate: changed
LOWAug 1, 2026NCT06793215lastUpdatePostDate: changed

Frequently asked questions about Divarasib

What is Divarasib used for?

Divarasib is an investigational small molecule being studied for the treatment of KRAS G12C-positive advanced or metastatic non-small cell lung cancer, as well as for hepatic impairment and in healthy participants for drug interaction studies. It is being developed by Roche Holding AG and is currently in Phase 1 clinical development.

What does Divarasib target?

Divarasib targets the KRAS G12C mutation, a specific genetic alteration found in some cancers, particularly non-small cell lung cancer. The drug is designed to inhibit the activity of this mutated KRAS protein, which drives tumor growth. This targeted approach is being evaluated in clinical trials for patients with KRAS G12C-positive advanced or metastatic non-small cell lung cancer.

Who makes Divarasib?

Divarasib is being developed by Roche Holding AG, a multinational healthcare company. Roche is conducting clinical trials to evaluate the safety and efficacy of Divarasib in various patient populations, including those with KRAS G12C-positive non-small cell lung cancer and healthy participants for pharmacokinetic studies.

What phase is Divarasib in?

Divarasib is currently in Phase 1 clinical development. While it is being studied in a Phase 3 trial for non-small cell lung cancer, the overall development program is in early stages, with multiple Phase 1 trials completed or ongoing. Divarasib is investigational and has not been approved by regulatory authorities.

What clinical trials is Divarasib in?

Divarasib is being evaluated in several clinical trials, including NCT06497556, a Phase 3 study comparing it to sotorasib or adagrasib in previously treated KRAS G12C-positive advanced or metastatic non-small cell lung cancer. Other trials include NCT06677957, NCT06690138, and NCT06835465, which are Phase 1 studies in healthy participants to assess drug interactions.

Is Divarasib the same as sotorasib or adagrasib?

No, Divarasib is a distinct investigational drug being developed by Roche. It is being compared directly against sotorasib and adagrasib in a Phase 3 clinical trial for KRAS G12C-positive non-small cell lung cancer. While all three target the KRAS G12C mutation, they are separate compounds with different chemical structures and development programs.