On September 13, 2026 GSK plc (LSE/NYSE: GSK) reported positive results from the registrational phase I/II ARROS-1 trial evaluating Jideytro (zidesamtinib) in patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who had not received previous treatment with a tyrosine kinase inhibitor (TKI-naïve). The data were presented in a Presidential Symposium session at the 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea, and will support a planned supplemental New Drug Application to the US FDA this year to expand the indication for Jideytro to include first-line treatment.

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In the 94 TKI-naïve patients included in the analysis, zidesamtinib achieved a clinically meaningful 94% objective response rate (ORR) (88/94; 95% CI: 87-98), including a 15% complete response rate (14/94), after a median follow-up of 15.2 months (range 1.1–30.5). Responses were durable, with 94% of patients continuing to respond to treatment at nine months and 86% at 12 months. Progression-free survival (PFS) was 90% at 12 months. Median duration of response (DOR) and median PFS had not been reached at the time of analysis. In the trial, 100% of patients with measurable brain metastases at baseline (n=10) responded to zidesamtinib (10/10, 95% CI: 69–100), and 70% achieved a complete clearance of detectable brain tumours (7/10). At 12 months, 78% of patients maintained an intracranial response, and no central nervous system progression events were observed among patients without brain metastases at baseline.1

Hesham Abdullah, Senior Vice President, Global Head of Oncology, R&D, GSK said, "Today’s results show a combination of high response rates and a tolerability profile that helped most patients stay on treatment. They highlight the potential for a differentiated profile for zidesamtinib to become a first-line treatment for patients with ROS1-positive NSCLC – a condition where maintaining long-term disease control, managing spread to the brain and minimising treatment-related side effects remain key challenges. We look forward to sharing these data with regulators."

Low rates of treatment discontinuation were observed, consistent with previous safety reports for zidesamtinib. The most common (≥15%) treatment-related adverse events (TRAEs) were peripheral oedema, weight increase, blood creatine phosphokinase increase, dysgeusia and aspartate aminotransferase increase; most were low grade. TRAEs led to dose reductions in 11% of patients and discontinuation in 1%.1

Alexander Drilon, MD, ARROS-1 primary investigator and Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, said: "Patients with ROS1-positive NSCLC may receive treatment for many years while continuing to work, care for their families and live their daily lives. They need treatments that provide lasting control of their disease, including in the brain, while limiting side effects and treatment disruption. The durable responses and low rates of treatment discontinuation observed in ARROS-1 represent encouraging progress toward addressing these long-term treatment needs."

Zidesamtinib is not approved anywhere in the world for use as first-line therapy. In July 2026, the FDA approved zidesamtinib for patients with ROS1-positive NSCLC previously treated with a TKI.2

About ARROS-1
The global, single-arm, first-in-human phase I/II ARROS-1 study (NCT05118789) included a phase II cohort of patients with locally advanced or metastatic ROS1-positive NSCLC who were naïve to ROS1 tyrosine kinase inhibitor (TKI) therapy, with up to one prior line of chemotherapy and/or immunotherapy permitted. Of 532 patients with ROS1-positive NSCLC who received zidesamtinib 100 mg once daily across all lines of therapy, 183 were receiving their first TKI-targeted treatment. The efficacy-evaluable population (n=94) included patients with measurable disease (by blinded independent central review) who initiated treatment by 15 June 2025, to allow at least nine months of follow-up for duration of response. 27% had received prior chemotherapy, 17% of whom also had prior immunotherapy. 17% had baseline central nervous system metastases by BICR. Data cut-off was 16 April 2026.

About ROS1-positive NSCLC
ROS1 mutations occur in approximately 2% of non-small cell lung cancers, contributing to an estimated 50,000 new diagnoses worldwide each year, typically in younger patients and more often in non-smokers. The disease has a high propensity to spread to the central nervous system, with brain metastases present in up to 40% of patients at diagnosis and remaining a common site of disease progression during treatment. Despite advances in targeted therapies, unmet need remains due to challenges including central nervous system progression, acquired resistance and treatment tolerability.3-6

About Jideytro
Jideytro (zidesamtinib), part of GSK’s portfolio from the recently completed acquisition of Nuvalent, Inc.7, was designed as a ROS1 TKI with broad coverage of ROS1 resistance mutations, activity against disease that has spread to the brain, durable treatment responses and a tolerable profile. Together, these features aim to help patients maintain disease control for longer while reducing the treatment challenges that can emerge over time.

Jideytro is FDA approved for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who received a prior ROS1 TKI.

(Press release, GlaxoSmithKline, SEP 13, 2026, View Source [SID1234670817])

On September 13, 2026 Summit Therapeutics Inc. (NASDAQ: SMMT) reported that its partner Akeso Inc. provided updated data, including overall survival (OS), from the randomized, double-blind Phase III HARMONi-2 trial featuring the novel, potential first-in-class investigational bispecific antibody ivonescimab is being presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC 2026) in Seoul, Republic of Korea.

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The HARMONi-2 presentation entitled, Overall Survival Analysis From HARMONi-2: Ivonescimab vs Pembrolizumab as First-Line Treatment for PD-L1-Positive NSCLC, evaluated ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 Score >1%). HARMONi-2 (AK112-303) is a single-region, multi-center Phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.

The trial results will be presented by Professor Caicun Zhou, MD, PhD, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President of IASLC, on Tuesday September 15, 2026.

Clinically Meaningful Efficacy
In this protocol-specified interim analysis of OS, a secondary endpoint in the HARMONi-2 study, ivonescimab monotherapy demonstrated a statistically significant and clinically meaningful improvement compared to pembrolizumab monotherapy, achieving a hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.95; p=0.009). A clinically meaningful benefit was demonstrated across important clinical subgroups, including those with PD-L1 low expression (PD-L1 Score 1-49%) and PD-L1 high expression (PD-L1 Score ≥ 50%), along with those with squamous and non-squamous histologies.

HARMONi-2 ITT (n=398)

Ivonescimab

Pembrolizumab

Median Follow-up: 36.0 mos

(n=198)

(n=200)

Median OS

30.8 mos

22.6 mos

OS Stratified HR

0.73

(95% CI: 0.57, 0.95; p=0.009)

ITT = intention-to-treat population; mos = months; CI = confidence interval

HARMONi-2 Subgroup Analyses; Ivonescimab vs. Pembrolizumab

Ivonescimab vs. Pembrolizumab

Descriptive, not formally powered

PD-L1 High (PD-L1 Score ≥50%)

HR = 0.58

n=168

(95% CI: 0.38, 0.89)

PD-L1 Low (PD-L1 Score 1-49%)

HR = 0.85

n=230

(95% CI: 0.61, 1.18)

Squamous Histology

HR = 0.65

n=181

(95% CI: 0.45, 0.95)

Non-Squamous Histology

HR = 0.79

n=217

(95% CI: 0.55, 1.14)

NR = not reached; mos = months; CI=confidence interval; n = number

Manageable Safety Profile
In this analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-2 study, which was consistent with previous Phase III studies of ivonescimab. No additional safety signals were noted in the HARMONi-2 study in this current data cut with longer treatment duration (median of 14 cycles of ivonescimab vs. 10 cycles of pembrolizumab) compared to the previous data cut.

Treatment-Related Adverse Events

Ivonescimab

(n=198)

Pembrolizumab

(n=200)

Median follow-up: 36.0 mos

Serious TRAEs, n (%)

59 (29.9)

43 (21.6)

TRAEs Leading to Discontinuation, n (%)

8 (4.1)

10 (5.0)

TRAEs = treatment-related adverse events; n = number; mos = months

Akeso received marketing authorization for ivonescimab from China’s National Medical Products Administration (NMPA) based on the results of HARMONi-2 in April 2025. In the study’s primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, progression-free survival (PFS) by Independent Radiologic Review Committee (IRRC), when compared to pembrolizumab monotherapy, achieving a hazard ratio (HR) of 0.51 (95% CI: 0.38, 0.69; p<0.0001).1

"HARMONi-2 is the fourth Phase III study of ivonescimab to demonstrate statistically significant improvements for both overall survival and progression-free survival in head-to-head comparisons against standard-of-care regimens," said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit Therapeutics. "Demonstrating a survival benefit against pembrolizumab monotherapy in this setting further strengthens our conviction that ivonescimab has the potential to advance treatment beyond PD-1 blockade alone and define what a next-generation immuno-oncology therapy can deliver for patients with lung cancer."

"Positive overall survival results in HARMONi-2 mark a pivotal moment for ivonescimab and underscore the promise of its differentiated PD-1 / VEGF bispecific approach," said Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. "These data build on the study’s previously reported progression-free survival benefit, while further informing our confidence in the broader ivonescimab development program, including HARMONi-7, our ongoing global Phase III study evaluating ivonescimab monotherapy against pembrolizumab monotherapy in patients with PD-L1 high-expressing metastatic non-small cell lung cancer."

Global Phase III HARMONi-7 Study
Based on the primary analysis results of HARMONi-2, Summit initiated the global HARMONi-7 study (NCT06767514) in early 2025. HARMONi-7 is a randomized, double-blind, multi-regional Phase III clinical trial evaluating ivonescimab monotherapy to pembrolizumab monotherapy in the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 Score > 50%). The study is currently recruiting, with a target enrollment of 780 patients globally. The co-primary endpoints of HARMONi-7 are PFS and OS.

The HARMONi-2 study is being conducted by Akeso in China, where ivonescimab is approved and commercially available for indications in NSCLC. Ivonescimab remains investigational and is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe.

About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of ivonescimab’s design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025) and increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 4,000 patients have been treated with ivonescimab in clinical studies globally and over 70,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.

There are currently 16 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, five of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into colorectal cancer (CRC) in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3. In 2026, Summit announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (bladder cancer) with global clinical trial site activations planned to begin by the fourth quarter of 2026.

HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.

HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering.

HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

HARMONi-GU1 is a Phase II/III clinical trial evaluating ivonescimab plus the antibody drug conjugate (ADC) enfortumab vedotin (EV) compared to pembrolizumab plus EV as first-line therapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.

Five Phase III ivonescimab clinical trials have read out to date, all five with positive data. Four of these five studies are in NSCLC, and one is in biliary tract cancer (BTC). In addition to Summit’s positive HARMONi study, Akeso has had positive read-outs in three single-region (China), randomized Phase III clinical trials in NSCLC, HARMONi-A, HARMONi-2, and HARMONi-6, including a statistically significant overall survival benefit in all three studies. Akeso has also reported a statistically significant OS benefit in the single-region (China), randomized Phase III HARMONi-GI1 trial in advanced BTC.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-GI1 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with durvalumab plus chemotherapy as a first-line treatment for patients with advanced BTC.

Akeso is actively conducting additional Phase III clinical studies in settings outside of NSCLC and biliary-tract cancer, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.

(Press release, Summit Therapeutics, SEP 13, 2026, View Source [SID1234670787])

On September 13, 2026 Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) reported results from the Phase 3 REZILIENT3 trial evaluating zipalertinib plus chemotherapy versus chemotherapy alone in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation-positive non-small cell lung cancer (NSCLC). The data were presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea.

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As previously announced, REZILIENT3 met its primary endpoint of progression-free survival (PFS). The results released today show that the addition of zipalertinib to platinum-based chemotherapy provided a statistically significant and clinically meaningful median PFS improvement of 6.0 months (HR=0.50; 95% CI, 0.34-0.73; P=0.00015) as first-line treatment for advanced NSCLC patients with EGFR ex20ins mutations. At the interim overall survival analysis (30% event maturity), the hazard ratio for death for zipalertinib plus chemotherapy versus chemotherapy was 0.72 (95% CI, 0.42-1.23) with follow up ongoing.

"The combination of zipalertinib plus platinum-based chemotherapy in the REZILIENT3 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations," said Helena A. Yu, MD, Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator. "The combination also produced significantly higher response rates compared with chemotherapy alone. These findings support the potential of zipalertinib plus platinum-based chemotherapy as a first-line treatment option for this patient population. We are grateful to the patients and their families, as well as the investigators whose dedication made these results possible."

These late-breaking results from the planned interim analysis of REZILIENT3 were selected for presentation in the Presidential Symposium 2 at IASLC 2026 WCLC. The Presidential Symposium 2 is a premier plenary session featuring notable advances in lung cancer research and treatment with the potential to change clinical practice.

"The findings presented add to previously presented single agent zipalertinib data and support the potential of zipalertinib across multiple treatment settings. We are thankful to patients, their families, and caregivers for participation in REZILIENT3," said Harold Keer, MD, PhD, Chief Medical Officer of Taiho Oncology. "We are excited to discuss these results further with health authorities and collaborate to make zipalertinib available to patients in a timely manner."

"We believe these results mark a potentially important step forward in the treatment of EGFR exon 20 insertion mutation-positive non-small cell lung cancer," said Fabio Benedetti, MD, Global Chief Medical Officer, Taiho Pharmaceutical. "To address the unmet medical needs of patients and their families, we will continue working closely with Taiho Oncology and Cullinan to make this treatment available to patients who may benefit from it."

"The selection of REZILIENT3 for presentation in a Presidential Symposium reflects the importance of these findings for the lung cancer community," said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. "The magnitude of progression-free survival benefit, together with improvements in response rates and duration of response seen in REZILIENT3, reinforce the potential for zipalertinib plus chemotherapy to play an important role in the first-line treatment of patients with EGFR exon 20 insertion mutation NSCLC."

Summary of Results:

After a safety lead-in (n=6), a total of 279 advanced NSCLC patients with EGFR ex20ins and no prior treatment for advanced disease were randomly assigned to receive zipalertinib 100mg BID plus chemotherapy (n=140) or chemotherapy alone (n=139). Baseline characteristics were balanced between the combination and the control arm, including age (66.5 vs. 64 years), sex (65.7% vs. 63.3% female), and brain metastases (31.4% vs. 31.7%), respectively.

At the pre-planned interim efficacy analysis after 122 PFS events, treatment with zipalertinib plus chemotherapy led to significantly longer median PFS than chemotherapy alone (14.5 vs. 8.5 months; HR: 0.50; 95% CI 0.34-0.73; P=0.00015). This PFS benefit was consistent across subgroups, including patients with brain metastases (HR: 0.38).

Objective response rate was higher with the combination therapy (65.0% vs. 40.3%), P<0.0001, with a longer median duration of response (14.2 vs. 9.9 months). At the interim overall survival (OS) analysis (30% maturity), the hazard ratio for death for zipalertinib plus chemotherapy as compared with chemotherapy was 0.72 (95% CI, 0.42-1.23). Continued follow-up of REZILIENT3 is ongoing to further characterize the OS benefit and exploratory endpoints (ClinicalTrials.gov number NCT05973773).

Summary of Preliminary Safety and Tolerability:

The observed adverse event (AE) profile of zipalertinib plus chemotherapy was generally consistent with the known safety profiles of the individual agents, and no new safety signals were observed. Grade ≥3 AEs occurred more frequently with the combination (87.1% vs. 54.4%), but these were primarily manageable hematologic AEs (58.6% vs. 28.7%). Grade ≥3 EGFR-related toxicities were infrequent, and those observed only in the combination arm included rash (10.7%) and diarrhea (1.4%).

Session information for the data presentation at WCLC 2026 is listed below:

Title: Zipalertinib plus Chemotherapy for 1st-line NSCLC with EGFR Exon 20 Insertions: Results from the Phase 3 Trial (REZILIENT3)
Presenting Author: Dr. Daniel Tan Shao Weng, Duke Health, Singapore
Session Name: PL03 Presidential Symposium 2 Including Lectureship Award Presentations
Session Type: Presidential Symposium 2, a premier plenary session featuring notable advances in lung cancer research and treatment
Session Date: Monday, September 14, 2026
Session Time: 8 a.m. KST
Location: Plenary, Hall D2, 3F

About the REZILIENT3 Trial

This multicenter, randomized, controlled, open-label global trial enrolled 285 adults with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. The primary objective of this trial is to assess progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm.

About Zipalertinib

Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations

NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins.1 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,1 with insertions at exon 20 accounting for up to 12% of these mutations.

(Press release, Taiho, SEP 13, 2026, View Source [SID1234670786])

On September 13, 2026 Daiichi Sankyo reported positive results from the DESTINY-Lung04 phase 3 trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a first-line treatment of patients with unresectable, locally advanced or metastatic HER2 mutant non-squamous non-small cell lung cancer (NSCLC). Results were presented today (#PL03.08) in Presidential Symposium 2 at the IASLC 2026 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC26).

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Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN).

In the primary endpoint analysis, Enhertu monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] = 0.63; 95% confidence interval [CI]: 0.50-0.79; p<0.0001). Median PFS was 14.3 months (95% CI: 12.4-16.5) with Enhertu compared to 8.3 months (95% CI: 7.0-9.9) for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for Enhertu across key subgroups, including the prespecified stratification factors of presence or history of brain metastases, smoking status, HER2 mutation status (exon 19 or exon 20), de novo or recurrent disease and presence of liver metastases.

Objective response rate (ORR) with Enhertu was 70.0% (95% CI: 63.6-75.9) versus 44.5% (95% CI: 37.9-51.2) with pembrolizumab plus chemotherapy. Median duration of response (DOR) for Enhertu was 13.4 months (95% CI: 10.4-17.2) and 9.7 months (95% CI: 7.0-11.1) with pembrolizumab plus chemotherapy. Median PFS2 (time from treatment start to second tumor progression or death from any cause) with Enhertu was 22.7 months (95% CI: 20.3-26.3) compared to 17.3 months (95% CI: 15.6-21.8) with pembrolizumab plus chemotherapy.

At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2 directed therapies in the pembrolizumab plus chemotherapy arm versus the Enhertu arm (48.0% versus 23.3%), and limited use of subsequent immunotherapy plus chemotherapy in the Enhertu arm (23.8%).

"HER2 mutant non-small cell lung cancer is an aggressive disease with limited responses to current first-line standard of care and many patients experience disease progression within a year of starting treatment," said Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and Lead Investigator of the DESTINY-Lung04 Trial. "With 70 percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new first-line treatment option for these patients."

The safety profile of Enhertu observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety signals identified. Grade 3 or higher treatment related adverse events (TRAE) occurred in 34.1% of patients treated with Enhertu. The most common grade 3 or higher TRAE occurring in 5% or more of patients treated with Enhertu was neutropenia (11.1%). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with Enhertu as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 [n=7; 3.1%] or grade 2 [n=30; 13.3%]). There were five (2.2%) grade 3, one (0.4%) grade 4 and four (1.8%) grade 5 ILD events in the Enhertu arm.

"Enhertu was the first HER2 directed medicine and antibody drug conjugate approved for patients with HER2 mutant non-small cell lung cancer and has become a second-line standard of care treatment," said John Tsai, MD, Global Head of R&D, Daiichi Sankyo. "The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of Enhertu in the first-line setting where delaying disease progression for as long as possible is a critical goal."

"DESTINY-Lung04 is the first phase 3 trial to demonstrate superior progression-free survival versus the global first-line standard of care in patients with HER2 mutant advanced non-small cell lung cancer," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "These results add to the growing body of evidence supporting Enhertu as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes."

Patients in the DESTINY-Lung04 trial received prior radiotherapy, chemotherapy, immunotherapy or targeted therapy for early-stage disease. Approximately three-quarters (75.8%) of the patients in the Enhertu arm had de novo disease, meaning the lung cancer was first diagnosed in the metastatic setting, and nearly one-quarter (22.9%) had brain metastases at baseline. Median duration of follow-up was 21.6 months with patients receiving Enhertu and 20.4 months with patients receiving pembrolizumab plus chemotherapy. As of the data cut-off date of June 9, 2026, 50 patients remained on study treatment with 40 patients still receiving Enhertu and 10 patients receiving pembrolizumab plus chemotherapy.

Summary of DESTINY-Lung04 Primary Results

Efficacy Measure

Enhertu (5.4 mg/kg)
(n=227)

Pembrolizumab plus
Chemotherapy
(n=227)

Median PFSi, (months) (95% CI)

14.3 months (12.4-16.5)

8.3 months (7.0-9.9)

HR = 0.63 (0.50-0.79); p<0.0001

ORRii (%) (95% CI)

70.0% (63.6-75.9)

44.5% (37.9-51.2)

CRi,iii, % (n)

1.8% (4)

1.8% (4)

PRi,iii, % (n)

68.3% (155)

42.7% (97)

SDi,iii, % (n)

26.9% (61)

43.2% (98)

Median DORi, (months) (95% CI)

13.4 months (10.4-17.2)

9.7 months (7.0-11.1)

Median PFS2iv, (months) (95% CI)

22.7 months (20.3-26.3)

17.3 months (15.6-21.8)

HR = 0.80 (0.62-1.02)

Median OSv, (months) (95% CI)

29.3 months (26.2-33.4)

33.1 months (27.7-40.7)

HR = 1.15 (0.88-1.52)

CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease
i Assessed by BICR
ii ORR is (CR + PR)
iii Includes unconfirmed responses
iv Assessed by investigator
v At DCO, overall data maturity for OS was 46.9%. No formal hypothesis testing was performed at this interim analysis; formal hypothesis testing will be performed at the second interim analysis and final analysis

About DESTINY-Lung04
DESTINY-Lung04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation.

Patients were randomized 1:1 to receive either Enhertu or standard of care. Randomization was stratified by smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY-Lung04 is PFS as assessed by BICR. Secondary endpoints include OS, investigator-assessed PFS, ORR and DOR as assessed by BICR and investigator, investigator-assessed PFS2, pharmacokinetics and safety.

DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Mutant NSCLC
Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related death.1 In 2024, approximately 2.6 million new lung cancer cases were reported worldwide, with an estimated 1.8 million deaths.1 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases.2 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five years after diagnosis.3,4,5

HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumor types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2% to 4% of patients with non-squamous NSCLC.6,7,8,9 These HER2 mutations are predominantly seen in younger women and people with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.6,10,11,12,13,14

The current global standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC has been a combination of immunotherapy and doublet platinum-based chemotherapy.15,16,17 Response rates with this treatment regimen have been limited and many patients experience disease progression, underscoring the need for additional treatment options.18

About Enhertu
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4 mg/kg) followed by THP is approved in Brazil, China, India, Singapore, Taiwan and the U.S. as a neoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4 mg/kg) is approved in Brazil, Canada, India and the U.S. for the adjuvant treatment of adult patients with HER2 positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial.

Enhertu (5.4 mg/kg) in combination with pertuzumab is approved in more than 40 countries/regions worldwide as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer, as determined by a locally or regionally approved test, based on the results from the DESTINY-Breast09 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.

Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the Enhertu Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of Enhertu as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.

(Press release, Daiichi Sankyo, SEP 13, 2026, View Source [SID1234670784])

On September 13, 2026 Akeso, Inc. (9926.HK) reported the presentation of positive overall survival (OS) results from the randomized, double-blind, multicenter, registrational Phase III HARMONi-2 study (AK112-303) at the 2026 World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC). The study evaluated the company’s first-in-class next-generation immuno-oncology therapy, ivonescimab, versus pembrolizumab as first-line treatment for patients with PD-L1-positive (PD-L1 TPS ≥1%) locally advanced or metastatic non-small cell lung cancer (NSCLC).

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The findings were selected as a Late-Breaking Abstract (LBA) for oral presentation and included in the official WCLC press program.

On September 13, the WCLC official website published the Abstract data on overall survival (OS) from the HARMONi-2 study. On September 15, Professor Caicun Zhou, Principal Investigator of HARMONi-2, IASLC President, and Director of the Department of Oncology at Shanghai East Hospital, will deliver the formal oral presentation (Oral) at the conference, sharing the complete results of the HARMONi-2 study with the global industry.

As of the data cutoff on August 20, 2026, the median follow-up was 36 months, and a total of 234 overall survival (OS) events had occurred. For this OS analysis, a prespecified O’Brien-Fleming spending function was used, with a one-sided alpha of 0.0141.

Results showed that, compared with pembrolizumab, first-line treatment with ivonescimab significantly prolonged OS in patients with PD-L1-positive advanced NSCLC. This finding met the prespecified statistical significance threshold and demonstrated clear clinical benefit. The overall survival benefit was generally consistent across prespecified subgroups, with particularly pronounced benefit observed in the PD-L1-high population.

1. Intention-to-Treat (ITT) Population: Median OS of 30.8 Months with Ivonescimab, 27% Reduction in Risk of Death

In the ITT population, ivonescimab monotherapy significantly prolonged OS versus pembrolizumab, with median OS of 30.8 months versus 22.6 months (HR=0.73; 95% CI: 0.57–0.95; P=0.009), corresponding to a 27% reduction in the risk of death.
2. Overcoming Traditional Anti-VEGF Treatment Contraindications: No Significant Increase in Bleeding Risk Observed in High-Risk Squamous Patients

Squamous NSCLC patients accounted for 45.5% of the HARMONi-2 population, and non-squamous patients for 54.5%. Among squamous patients treated with ivonescimab, 72.2% had central tumors, 10.0% had tumor cavitation or necrosis, and 6.7% had tumors encasing major vessels.

These populations are traditionally considered contraindicated or high-risk for anti-VEGF therapies and have long lacked effective treatment options. However, no apparent increase in bleeding risk was observed with ivonescimab, and these patients showed favorable benefit.

3. Consistent OS Benefit with Ivonescimab Regardless of PD-L1 Expression Level, with Particularly Pronounced Benefit in the TPS ≥50% Population

In the PD-L1 TPS ≥50% subgroup, OS HR=0.58 (95% CI: 0.38–0.89), corresponding to a 42% reduction in the risk of death.
In the PD-L1 TPS 1–49% subgroup, OS HR=0.85 (95% CI: 0.61–1.18), corresponding to a 15% relative reduction in the risk of death.
4. Consistent OS Benefit with Ivonescimab Regardless of Histology (Squamous and Non-Squamous)

In the squamous cell carcinoma subgroup, OS HR=0.65 (95% CI: 0.45–0.95), corresponding to a 35% reduction in the risk of death.
In the non-squamous subgroup, OS HR=0.79 (95% CI: 0.55–1.14), corresponding to a 21% reduction in the risk of death.
5. Favorable Overall Safety Profile with No New Safety Signals; Safety Characteristics Generally Consistent Between Arms

In May 2024, a prespecified interim analysis of progression-free survival (PFS) assessed by the Independent Data Monitoring Committee (IDMC) confirmed that HARMONi-2 met its primary PFS endpoint with statistically significant and clinically meaningful results. Median PFS was 11.14 months with ivonescimab versus 5.82 months with pembrolizumab (HR=0.51, P<0.0001). This indication was approved in China in 2025.

HARMONi-2 is the first randomized, double-blind, controlled Phase III clinical study to demonstrate statistically significant positive OS and PFS results versus pembrolizumab.

An international multicenter Phase III clinical study evaluating ivonescimab monotherapy versus pembrolizumab as first-line treatment for PD-L1-high NSCLC (HARMONi-7/AK112-3007) is currently progressing efficiently.

To date, ivonescimab has consistently achieved dual-positive OS and PFS results across multiple Phase III head-to-head trials against PD-1/L1 therapies and continues to expand into major solid tumors beyond lung cancer. The synergistic antitumor effects of ivonescimab’s dual "immuno-oncology + anti-angiogenesis" mechanism continue to be validated in both clinical research and real-world settings. Ivonescimab has the potential to provide a more effective treatment option with a manageable safety profile for cancer patients worldwide and to drive continued progress in oncology care.

(Press release, Akeso Biopharma, SEP 13, 2026, View Source [SID1234670782])