Roche’s Divarasib Showcases Best-in-class Efficacy in Previously Treated KRAS G12C-mutated Lung Cancer; CLARITY-Gastric01 Shows 42% Lower Death Risk with Sonesitatug Vedotin; Lilly’s Olomorasib Shows Durable First-line Activity in KRAS G12C-mutant NSCLC; Izalontamab Brengitecan Doubles Median PFS in Phase 3 EGFR-Mutated NSCLC Trial; Novartis’ Remibrutinib Delivers Broad Disease Control with Consistent Safety in RMS

Roche’s Divarasib Sets a New Efficacy Benchmark in Previously Treated KRAS G12C-mutated Lung Cancer

Roche reported pivotal findings from the Phase III KRASCENDO 1 trial, demonstrating that investigational divarasib, a next-generation KRAS G12C inhibitor, delivered superior efficacy compared with currently available standard-of-care KRAS G12C inhibitors in patients with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Patients receiving divarasib monotherapy experienced significantly longer overall survival (OS), with a 44% reduction in the risk of death compared with those treated with sotorasib or adagrasib (OS hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.41–0.78; p=0.0005). Median OS with divarasib is currently approximately 18 months, compared with 12 months in the control group. No new safety signals were identified, and the most common treatment-related adverse events (TRAEs) were predominantly low-grade and manageable. The findings were presented as a late-breaking abstract during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and published concurrently in The New England Journal of Medicine.

According to Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, the KRASCENDO 1 results underscore divarasib’s potential to establish a new standard of care for patients with previously treated KRAS G12C-mutated lung cancer. He noted that the statistically superior efficacy demonstrated in this direct comparative trial further supports divarasib’s best-in-class potential. Roche is collaborating with regulatory authorities to make this treatment option available to patients who need it.

The KRAS G12C mutation is among the most prevalent KRAS alterations, occurring in approximately one in eight patients with NSCLC. Evidence increasingly indicates that patients with KRAS G12C-mutated NSCLC may experience poorer outcomes than those with wild-type KRAS disease. Although first-generation KRAS G12C-targeted therapies have received regulatory approval, substantial unmet medical needs remain, highlighting the demand for more effective treatment alternatives.

Ferdinandos Skoulidis, MD, PhD, Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center and lead author of the study, emphasized the urgent need for therapies that extend survival, as most patients with this cancer eventually experience relapse following initial treatment and effective options for recurrent disease remain limited. He highlighted the potential of the KRASCENDO 1 findings to change clinical practice, describing divarasib as the first KRAS inhibitor to demonstrate a meaningful overall survival improvement over existing treatment options in patients with previously treated KRAS G12C-mutated lung cancer.

KRASCENDO 1 is the only global head-to-head trial to assess a next-generation KRAS G12C inhibitor against approved first-generation inhibitors. The study achieved its primary and key secondary endpoints, with divarasib demonstrating statistically significant and clinically meaningful improvements in both OS and progression-free survival (PFS) compared with sotorasib or adagrasib. In addition to improving OS, divarasib reduced the risk of disease progression or death by 42% (PFS HR: 0.58; 95% CI: 0.44–0.76; p

Sonesitatug Vedotin Demonstrates a Survival Benefit in Advanced CLDN18.2-positive Gastric/GEJ Cancer

Positive findings from the global Phase III CLARITY-Gastric01 trial demonstrated that AstraZeneca’s investigational sonesitatug vedotin (Sone-Ve) achieved a statistically significant and clinically meaningful improvement in overall survival (OS) among patients with Claudin 18.2 (CLDN18.2)-positive advanced gastric cancer who had received two or more prior lines of treatment, compared with investigator’s choice of therapy.

The study enrolled patients with locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal adenocarcinoma (EAC) whose tumours expressed CLDN18.2 in at least 25% of tumour cells, regardless of staining intensity. This eligibility criterion extends the target patient population beyond the currently established definition of CLDN18.2 positivity. The findings were presented at a Presidential Symposium during the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain (abstract #LBA7).

The trial had two primary endpoints: OS among patients receiving third-line or later treatment and progression-free survival (PFS) in the overall study population treated in the second-line or later setting. OS in the overall study population was designated as a key secondary endpoint.

At a planned interim analysis, Sone-Ve reduced the risk of death by 42% compared with investigator’s choice of therapy in the overall study population (OS hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.47–0.73; p<0.000004). Median OS was 10.6 months with Sone-Ve, compared with 6.4 months with investigator’s choice of therapy.

Among patients treated in the third-line or later setting, Sone-Ve reduced the risk of death by 53% relative to investigator’s choice of therapy (OS HR 0.47; 95% CI 0.36–0.62; p<0.000001). Median OS doubled, reaching 10.0 months with Sone-Ve versus 5.0 months with the comparator treatment. The survival benefit was generally consistent across most predefined subgroups in both the overall population and the third-line or later subgroup, including patients with CLDN18.2 expression levels of ≥25% to <75% and ≥75%.

For the second primary endpoint, PFS assessed by blinded independent central review (BICR) in the overall study population, the results indicated a trend toward improvement among patients receiving Sone-Ve in the second-line or later setting; however, the difference did not achieve statistical significance. An exploratory analysis based on investigator-assessed PFS demonstrated a more pronounced treatment effect (PFS HR 0.59; 95% CI 0.48–0.73), consistent with the OS findings in this population.

New ESMO Data Spotlight Olomorasib’s First-line Potential in KRAS G12C-mutated NSCLC

Eli Lilly and Company presented new first-line clinical data for olomorasib, its investigational next-generation KRAS G12C inhibitor, at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. Poster results from the Phase 1/2 LOXO-RAS-20001 trial and the safety lead-in portion of the Phase 3 SUNRAY-01 trial evaluated olomorasib in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab), without chemotherapy, in patients with first-line KRAS G12C-mutated non-small cell lung cancer (NSCLC). After a median follow-up of nearly 21 months, median progression-free survival (PFS) and duration of response (DOR) had not yet been reached, with durable antitumor activity observed across different PD-L1 expression levels. In a separate rapid oral presentation, olomorasib combined with chemoimmunotherapy comprising pembrolizumab, pemetrexed, and platinum-based chemotherapy demonstrated an investigator-assessed overall response rate (ORR) of 62% and a median DOR of 14.5 months in patients with previously untreated advanced KRAS G12C-mutated NSCLC, following a median follow-up of nearly 19 months.

Dr. Marcelo V. Negrao, Associate Professor of Thoracic and Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center and the study’s presenting author, highlighted the significance of the findings, noting that responses lasting more than a year at the median across all PD-L1 tumor expression levels, including in many patients with low expression, represent meaningful progress in the first-line setting. He added that the ESMO findings support further investigation of olomorasib in combination with immunotherapy, with or without chemotherapy, potentially expanding initial treatment options for patients with lung cancer, similar to the advances achieved with genomically targeted therapies in other settings.

KRAS G12C mutations are present in approximately 13% of patients with NSCLC, the most common type of lung cancer. These patients often exhibit high-risk clinical features and a greater burden of comorbidities. Currently, no targeted therapies are approved specifically for first-line treatment of KRAS G12C-mutated NSCLC. Standard treatment generally involves immunotherapy, either alone or in combination with chemotherapy, while many patients do not proceed to second-line treatment. The development of KRAS G12C inhibitor combinations in this setting has also been constrained by toxicity concerns associated with certain immunotherapy combinations.

Olomorasib is a potent, selective, next-generation oral inhibitor designed to target the KRAS G12C mutation. It binds to the mutated protein and stabilizes it in an inactive state. Its pharmacological properties are intended to support high predicted target occupancy and potent activity, potentially enabling more tolerable and flexible combinations with standard-of-care immunotherapy, with or without chemotherapy.

Phase 3 Data Highlight PFS Advantage for Izalontamab Brengitecan in EGFR-Mutated NSCLC

SystImmune, Inc. and Bristol Myers Squibb announced positive findings from a prespecified interim analysis of the Phase 3 PANKU-Lung01 (NCT06382116) trial, reported by SystImmune’s parent company, Sichuan Biokin Pharmaceutical Co., Ltd.. The randomized, multicenter study evaluated izalontamab brengitecan (iza-bren), an investigational first-in-class, dual-targeting EGFRxHER3 bispecific antibody-drug conjugate (ADC), against platinum-based chemotherapy (PBC) in patients with EGFR-mutated non-squamous non-small cell lung cancer (NSCLC) previously treated with an EGFR tyrosine kinase inhibitor (TKI). The findings are scheduled for presentation in a late-breaking oral session at the European Society for Medical Oncology (ESMO) 2026 Annual Congress, being held October 23–27 in Madrid, Spain, and will be published simultaneously in The Lancet.

At a median follow-up of 14.6 months for progression-free survival (PFS), iza-bren demonstrated a statistically significant improvement in the trial’s primary endpoint compared with PBC. Blinded Independent Central Review (BICR) assessed median PFS at 11.1 months in the iza-bren group (n=216), compared with 5.7 months in the chemotherapy group (n=206), representing a 60% reduction in the risk of disease progression or death (HR: 0.40; 95% CI: 0.31–0.51; p<0.0001). Overall survival (OS), a secondary endpoint, remained immature at the time of analysis, although results indicated a favorable trend toward improved survival with iza-bren. The confirmed objective response rate (cORR) assessed by BICR was 60.2% with iza-bren versus 34.5% with PBC, while median duration of response (mDOR) was 10.4 months and 5.7 months, respectively.

Professor Li Zhang, Chief Lung Cancer Expert at Sun Yat-sen University Cancer Center, noted that treatment options remain limited for patients with EGFR-mutated NSCLC whose disease progresses following EGFR TKI therapy, with chemotherapy frequently used despite its modest survival benefits. He highlighted that the PANKU-Lung01 results indicate iza-bren’s potential to alter the disease course by extending the time before progression, potentially representing a meaningful advance in addressing acquired treatment resistance and improving patient outcomes.

Iza-bren demonstrated a manageable safety profile, with no new safety signals identified in the study population. Grade 3 or higher treatment-related adverse events (TRAEs) were primarily hematologic and could be managed with standard supportive care. Treatment discontinuation due to TRAEs occurred in just 1.9% of patients receiving iza-bren. Interstitial lung disease (ILD) was infrequent, with two adjudicated cases (0.9%), including one Grade 3 event and one Grade 1 event.

The investigational ADC has demonstrated clinical benefit across five Phase 3 trials spanning five distinct indications: previously treated EGFR-mutated NSCLC, previously treated nasopharyngeal carcinoma, previously treated esophageal squamous cell carcinoma, advanced triple-negative breast cancer, and previously treated hormone receptor-positive (HR+)/HER2-negative breast cancer. These findings highlight its potential across multiple cancer types with significant unmet treatment needs. In addition, the U.S. Food and Drug Administration (FDA) has granted iza-bren Breakthrough Therapy Designation for previously treated advanced EGFR-mutated NSCLC.

The PANKU-Lung01 trial is sponsored by Biokin in mainland China. Outside China, iza-bren is being jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive licensing agreement.

Novartis’ Remibrutinib Showed Comprehensive Disease Control And Consistent Safety Across Phase III Trials in RMS

Novartis announced positive findings from the pivotal Phase III REMODEL-1 and REMODEL-2 trials evaluating remibrutinib in patients with relapsing multiple sclerosis (RMS). The results demonstrated that remibrutinib, a highly selective and potent oral Bruton’s tyrosine kinase (BTK) inhibitor, provided superior relapse control and a clinically meaningful delay in disease progression compared with teriflunomide, without showing a liver safety signal. The findings were presented during a late-breaking session at MSToronto2026, the 10th Joint ACTRIMS-ECTRIMS Meeting, and were published concurrently in The Lancet.

According to Prof. Dr. Heinz Wiendl, Professor of Neurology and Chair of the Department of Neurology and Neurophysiology at the Medical Center, University of Freiburg, the REMODEL trials demonstrated that oral remibrutinib significantly reduced relapse activity and produced a clinically meaningful effect on confirmed disability progression in people with relapsing MS. He noted that as treatment objectives in MS increasingly extend beyond relapse prevention, the observed efficacy and favorable safety profile indicate that remibrutinib could offer a differentiated and meaningful treatment option for patients with RMS.

Remibrutinib significantly reduced the annualized relapse rate (ARR), the primary endpoint of both studies, compared with teriflunomide. In REMODEL-1, the ARR was 0.073 with remibrutinib versus 0.112 with teriflunomide, while REMODEL-2 reported rates of 0.080 and 0.116, respectively. These results corresponded to statistically significant and clinically meaningful relative reductions of 35.2% and 31.2%, respectively, equivalent to approximately one relapse every 13 years. Remibrutinib also demonstrated a clinically meaningful delay in disability progression, lowering the risk of 6-month confirmed disability progression (6mCDP) by 29.2%, with nominal statistical significance. Additionally, the treatment showed a consistent positive trend toward a 20.5% reduction in the risk of 3-month confirmed disability progression (3mCDP). Over the 24-month study period, more than 92% of patients treated with remibrutinib remained free from disease progression, as measured by 6mCDP.

Beyond its efficacy, remibrutinib demonstrated a favorable hepatic safety profile, with no liver safety signal and no reported cases of Hy’s Law, a serious indicator of potential drug-induced liver injury that has emerged in other late-stage BTK inhibitor development programs. Across both trials, liver enzyme elevations were less frequent among remibrutinib-treated patients across all assessed thresholds. Elevations in alanine aminotransferase (ALT) exceeding three times the upper limit of normal (ULN) occurred in 2.0% of patients receiving remibrutinib, compared with 7.4% of those treated with teriflunomide. The incidence in the remibrutinib group was consistent with rates observed in placebo groups in previous RMS trials. Furthermore, pooled analyses showed that treatment discontinuations due to adverse events (AEs) were nearly 50% lower with remibrutinib than with teriflunomide, at 3.1% and 5.8%, respectively.

Remibrutinib is a highly selective, covalent, orally administered BTK inhibitor that blocks BTK signaling, thereby reducing the activation of B cells and innate immune cells and modulating immune regulatory networks associated with neuroinflammation. Unlike approaches that rely on sustained B-cell depletion, remibrutinib is designed to regulate BTK signaling without causing chronic B-cell depletion, representing a differentiated strategy for immune modulation. In preclinical investigations, remibrutinib exhibited the highest BTK selectivity among the inhibitors evaluated.