KRASCENDO-1 at a Glance
Design
Phase III, randomized, open-label, multicenter, global head-to-head: divarasib monotherapy (once daily) vs sotorasib (once daily) or adagrasib (twice daily) — locally approved first-generation KRAS G12C inhibitors in 338 adults with previously treated (1–3 prior lines) KRAS G12C-mutant advanced or metastatic NSCLC. Primary endpoint: BICR-assessed PFS; key secondary: OS. Described by Genentech as “the only global head-to-head study evaluating a KRAS G12C inhibitor in direct comparison with first generation KRAS G12C inhibitors.” (Genentech press release; ClinicalTrials.gov)
Topline result — July 1, 2026
Met the primary and key secondary endpoints: clinically meaningful, statistically significant improvement in both PFS and OS for divarasib vs sotorasib or adagrasib, with statistical significance for overall survival achieved at the interim analysis. No medians, hazard ratios, or response rates have been released — full results will be presented at an upcoming medical meeting. (Genentech press release, 01-Jul-2026)
Safety
Per the press release, the safety profile of divarasib remained consistent with previous data, with no new findings; the most common treatment-related events were described as manageable and reversible. No per-arm safety data released. (Genentech press release, 01-Jul-2026)
Regulatory status
⚠️ Divarasib is investigational — not FDA approved in any setting; Genentech plans regulatory submissions based on these data. ✅ The comparators hold FDA ACCELERATED approvals for previously treated KRAS G12C+ NSCLC: sotorasib (Lumakras, Amgen; its full-approval application received a Complete Response Letter in December 2023) and adagrasib (Krazati, Bristol Myers Squibb). (Genentech press release; FDA)
KOL pulse
Patrick Forde called the result “An advance given all the negative or borderline trial results we have had after chemo & immunotherapy”; Stephen V Liu is “Eagerly awaiting data presentation”; Giannis Mountzios called it a “Significant press release” and a “@KRASKickers victory!”
KOLs Discussing KRASCENDO-1
What Physicians Said
Next gen Kras G12C, divarasib, improves survival in 2nd line lung cancer in Krascendo 1. An advance given all the negative or borderline trial results we have had after chemo & immunotherapy. Krascendo 2 (1st line advanced nsclc) & Krascendo 3 (adjuvant) trials ongoing! #lcsm https://t.co/zHEiQaEejn
Top-line results from randomized phase III Krascendo 1 trial shows divarasib superior to first generation KRAS G12C inhibitors with improved PFS and significant improvement in OS, meeting primary endpoint. Eagerly awaiting data presentation! https://t.co/u5RpqQZbto
Significant press release from KRASCENDO-1 trial showing that novel KRAS inhibitor divarasib significantly improves both PFS and OS compared to approved agents sotorasib and adagrasib in patients with KRAS G12C mut NSCLC @KRASKickers victory! https://t.co/22eLsmTgB4
About the KRASCENDO-1 Trial
Krascendo 1 (NCT06497556) asks the question the KRAS G12C field has debated since sotorasib and adagrasib were approved: can a next-generation inhibitor beat the first generation head-to-head? Divarasib is an investigational, oral KRAS G12C inhibitor designed for greater potency and selectivity; in its long-term phase I follow-up it showed a confirmed ORR of 59.1% and median PFS of 15.3 months in the 400 mg daily cohort (n=44; Sacher et al., J Clin Oncol) — numerically higher than the first-generation agents reported in their own early-phase studies, but cross-trial comparisons are unreliable. Krascendo 1 removed that caveat by randomizing 338 previously treated patients directly between divarasib and sotorasib or adagrasib (locally approved first-generation KRAS G12C inhibitors).
On July 1, 2026, Genentech announced the study met both its primary endpoint (BICR-assessed PFS) and key secondary endpoint (OS) with statistically significant, clinically meaningful improvements — the first head-to-head phase III superiority result within the KRAS G12C inhibitor class. “These results should establish divarasib as a new standard of care for previously-treated lung cancer patients with this genetically defined tumor subtype,” said Levi Garraway, MD, PhD, Genentech’s chief medical officer, in the press release. Numeric results have not been disclosed. Note the naming: Krascendo 1 is distinct from NAUTIKA1, the separate phase II umbrella testing neoadjuvant divarasib in resectable NSCLC.
Trial Methodology & Results
Study Design
Phase III, randomized, open-label, multicenter, global head-to-head. Divarasib monotherapy vs sotorasib or adagrasib (locally approved first-generation KRAS G12C inhibitors). (CTgov; Genentech PR)
Population
338 adults with KRAS G12C-mutant advanced or metastatic NSCLC and disease progression during or after 1–3 prior lines of systemic therapy. (Genentech PR; CTgov)
Interventions
Divarasib once daily vs sotorasib once daily or adagrasib twice daily (locally approved first-generation KRAS G12C inhibitors). (Genentech PR; CTgov)
Endpoints
Primary: PFS by blinded independent central review (RECIST v1.1). Key secondary: OS. Additional: confirmed objective response, duration of response, safety. (Genentech PR; CTgov)
Program Context
Krascendo 2 (NCT06793215): 1L non-squamous, divarasib + pembrolizumab vs pembrolizumab + pemetrexed-platinum. Krascendo 3 (NCT07541170): adjuvant divarasib vs immunotherapy or observation in resected stage II–IIIB disease, in patients without a pCR after neoadjuvant chemoimmunotherapy. Krascendo 170 (NCT05789082): Ph1b/2 first-line single-agent and combination cohorts. (Genentech PR; CTgov)
Topline efficacy — PFS and OS both met
The study met its primary and key secondary endpoints: divarasib achieved clinically meaningful and statistically significant improvements in both progression-free survival and overall survival versus the first-generation KRAS G12C inhibitors sotorasib or adagrasib, with statistical significance for OS achieved at the interim analysis. No numeric results (medians, hazard ratios, confidence intervals, or response rates) have been released — full results will be presented at an upcoming medical meeting and submitted to regulatory authorities. This page will be updated when the data are presented. (Genentech press release, 01-Jul-2026)
First positive phase III head-to-head vs first-generation KRAS G12C inhibitorsSource: Genentech press release, July 1, 2026 ↗
Safety — topline
Per the press release, the safety profile for divarasib remained consistent with previous data, with no new findings detected; the most common treatment-related events were manageable and reversible. In earlier reported phase I experience at 400 mg daily, gastrointestinal toxicities (nausea, vomiting, diarrhea) predominated and were largely low grade. Per-arm phase III safety data have not been released. (Genentech press release, 01-Jul-2026; phase I long-term follow-up, 400 mg cohort, Sacher et al., J Clin Oncol)
No new safety findings reported at toplineSource: Roche media release, July 2, 2026 ↗
KRASCENDO-1 FAQ
What is the KRASCENDO-1 trial?
Krascendo 1 (NCT06497556) is a Roche/Genentech phase III, randomized, open-label, multicenter study of divarasib — an investigational next-generation oral KRAS G12C inhibitor — versus the locally approved first-generation inhibitors sotorasib (Lumakras, once daily) or adagrasib (Krazati, twice daily) in 338 adults with previously treated (1–3 prior lines) KRAS G12C-mutant advanced or metastatic NSCLC. Genentech describes it as the only global head-to-head study evaluating a KRAS G12C inhibitor in direct comparison with first-generation KRAS G12C inhibitors. The primary endpoint is progression-free survival by blinded independent central review; overall survival is a key secondary endpoint.
What did the KRASCENDO-1 topline results show?
Per the Genentech press release of July 1, 2026, the study met its primary and key secondary endpoints: divarasib achieved clinically meaningful and statistically significant improvements in both progression-free survival and overall survival versus sotorasib or adagrasib, with statistical significance for overall survival achieved at the interim analysis. The safety profile was consistent with previous data with no new findings, and the most common treatment-related events were described as manageable and reversible. No numeric results (medians, hazard ratios, response rates) have been released — full data will be presented at an upcoming medical meeting.
Is divarasib FDA approved?
No. Divarasib is investigational and not FDA-approved in any setting. Genentech has stated it plans to submit the Krascendo 1 data to regulatory authorities. The comparators both hold FDA accelerated approvals for previously treated KRAS G12C-mutated NSCLC: sotorasib (Lumakras, Amgen) and adagrasib (Krazati, Bristol Myers Squibb).
How is KRASCENDO-1 different from the NAUTIKA1 trial?
They are two different studies of the same drug. Krascendo 1 (NCT06497556) is a phase III trial of divarasib monotherapy in previously treated ADVANCED or metastatic KRAS G12C+ NSCLC. NAUTIKA1 (NCT04302025) is a separate phase II biomarker-directed umbrella study testing roughly 8 weeks of NEOADJUVANT targeted therapy — including divarasib in its KRAS G12C cohort — before surgery in resectable stage IB–IIIB NSCLC.
What other trials are in the divarasib KRASCENDO program?
Per Genentech, divarasib's phase III program spans the treatment continuum: Krascendo 1 (NCT06497556, previously treated advanced disease, versus sotorasib or adagrasib), Krascendo 2 (NCT06793215, first-line non-squamous disease, divarasib plus pembrolizumab versus pembrolizumab plus pemetrexed and platinum chemotherapy), and Krascendo 3 (NCT07541170, adjuvant divarasib versus immunotherapy or observation in resected stage II–IIIB disease, in patients without a pathologic complete response after neoadjuvant chemoimmunotherapy). The phase Ib/II Krascendo 170 study (NCT05789082) tests first-line combinations.
Key KOL Sentiments - KRASCENDO-1
Media Coverage
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Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated September 13, 2026. Sources: Genentech press release (July 1, 2026), Roche media release (July 2, 2026), ClinicalTrials.gov NCT06497556, and verbatim physician posts on X.