On September 14, 2026 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported the first median overall survival ("OS") data from the non-pivotal stage 1 of the global randomized PRESERVE-003 Phase 3 clinical trial (NCT05671510) of gotistobart (also known as BNT316 or ONC-392), in patients with squamous non-small lung cancer ("NSCLC") whose disease progressed on prior immunotherapy and chemotherapy. Gotistobart is an investigational CTLA-4-targeting immunotherapy designed to selectively deplete regulatory T cells ("Tregs") within the tumor microenvironment and restore anti-tumor immune activity.

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The data showed that treatment with gotistobart led to a statistically significant and clinically meaningful OS benefit, nearly doubling survival compared with standard-of-care chemotherapy in this patient population. The data were presented at the International Association for the Study of Lung Cancer ("IASLC") 2026 World Conference on Lung Cancer ("WCLC").

"Patients with squamous NSCLC continue to face limited treatment options after progression on immunotherapy. Current survival expectations with established therapies remain less than a year, and despite numerous development efforts, chemotherapy has remained the standard of care in this setting for more than a decade," said Rama Balaraman, M.D., Principal Investigator and medical oncologist at Ocala Oncology Center, Florida, United States. "The magnitude of the survival benefit observed with gotistobart as a chemotherapy-free treatment approach in the PRESERVE-003 clinical trial is highly encouraging. If confirmed in the pivotal portion of the Phase 3 trial, these findings could transform the standard of care in a setting where new therapies are urgently needed."

At the data cut-off on July 17, 2026, with a median follow-up of 25.4 months, 87 patients with metastatic squamous NSCLC had been randomized to receive either gotistobart monotherapy 6 mg/kg with two 10 mg/kg loading doses (N=45) or docetaxel 75 mg/m2 (N=42) in the second-line or later treatment setting. The median OS was 18.5 months for patients treated with gotistobart compared to 10.0 months for patients treated with docetaxel (HR: 0.56; nominal p-value=0.0295). The safety profile of gotistobart was consistent with previously reported data and remained manageable. Grade ≥3 treatment-related adverse events ("AEs") were reported in 20/45 (44.4%) patients receiving gotistobart and 20/42 (48.8%) patients receiving docetaxel.

"These data underscore gotistobart’s potential to redefine treatment for patients with hard-to-treat squamous NSCLC whose disease has progressed after initial therapy and who face limited options," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "In second- and later lines of treatment, the clinical relevance of novel therapeutic options depends on the ability to re-engage a suppressed or exhausted anti-tumor immune response and overcome acquired resistance. This update highlights gotistobart’s unique mode of action and our ambition to translate our deep understanding of the immune system into meaningful survival benefit for patients with lung cancer – particularly in areas where patients still need more. We look forward to continuing our work with our colleagues at OncoC4 to further explore and realize gotistobart’s full potential."

"The data support the differentiated mechanism of action of gotistobart as a tumor microenvironment-selective Treg modulator and reinforce our confidence in the therapeutic potential of this distinct CTLA-4-targeting approach to meaningfully shift the treatment landscape in this indication," said Pan Zheng, M.D., Ph.D., Co-Founder and Chief Medical Officer at OncoC4. "We are encouraged by the clinical activity and safety profile observed to date and remain focused on advancing gotistobart for patients with this difficult-to-treat disease."

The pivotal stage 2 portion of PRESERVE-003 is currently ongoing at more than 160 sites globally. Gotistobart previously demonstrated a clinically meaningful OS benefit and durable anti-tumor activity versus docetaxel in stage 1 of the PRESERVE-003 Phase 3 trial in patients with squamous NSCLC who had progressed on PD-(L)1 inhibitors. This data was published in Nature Medicine and presented at the 2026 European Lung Cancer Congress ("ELCC") and the IASLC ASCO (Free ASCO Whitepaper) 2025 North America Conference on Lung Cancer ("NACLC").

About the PRESERVE-003 clinical trial
PRESERVE-003 (NCT05671510; EUCT:2023-505311-20-01; CTR20232927) is a two-stage, open-label Phase 3 trial evaluating the efficacy and safety of gotistobart as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in squamous NSCLC patients, who have progressed on PD-(L)1 inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial included all NSCLC patients. The ongoing pivotal stage enrolled patients with squamous NSCLC. The primary endpoint is overall survival. Secondary endpoints include overall response rate, progression-free survival, and safety profile.

About gotistobart (BNT316/ONC-392)
Gotistobart (BNT316/ONC-392) is an investigational immunotherapy that enhances Treg depletion within the tumor microenvironment through targeting CTLA-4 to reignite antitumor immunity and which is being jointly developed by BioNTech and OncoC4.2,3,4,5,6,7,8,9 As a pH-sensitive monoclonal antibody, gotistobart is designed to enable CTLA-4 protein recycling. After binding to the CTLA-4 receptor on the cell surface, the complex is internalized, and the pH change causes the antibody to unbind, allowing CTLA-4 to return to the surface to preserve the immune checkpoint function at peripheral organs and to enhance anti-tumor immunity in the tumor microenvironment.9

Gotistobart is currently in late-stage clinical development as a monotherapy and as a component of combination therapy in various cancer indications. Gotistobart received Fast Track Designation from the U.S. Food and Drug Administration ("FDA") in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy and Orphan Drug Designation for the treatment of patients with squamous NSCLC in 2025. The candidate also received Breakthrough Therapy Designation from China’s National Medical Products Administration ("NMPA") in 2025.

About squamous non-small cell lung cancer
With a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000-2017), squamous NSCLC is a devastating disease with limited treatment options.1 Current standard-of-care includes surgery and radiotherapy in combination with chemotherapy.9 Treatment options for second-line therapy after first-line immunotherapy and chemotherapy are limited to chemotherapy or palliative therapy in advanced/metastatic squamous NSCLC and remain more limited than for non-squamous NSCLC.

(Press release, BioNTech, SEP 14, 2026, View Source [SID1234670815])

On September 14, 2026 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) , a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for autoimmune diseases, solid tumors and hematological malignancies indications, reported that a preclinical research paper evaluating the combination of ATG-037 (CD73 Small Molecule Inhibitor) and selinexor for the treatment of multiple myeloma (MM), conducted in collaboration with the Department of Hematology at Peking University Third Hospital, has been published in Cancer Gene Therapy, an international SCI journal under Springer Nature.

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Details of the Paper
Title: CD73 inhibitor enhances the antitumor activity of selinexor in multiple myeloma by restoring the activation of CD8+ T cells
Journal: Cancer Gene Therapy
DOI: 10.1038/s41417-026-01078-9

Study Design:

The research team first analyzed CD73 expression across multiple tumor cell lines following selinexor treatment, then tested the combination in vivo using a J558-inoculated BALB/c mouse model, with mice divided into a vehicle group, an ATG-037 monotherapy group, a selinexor monotherapy group and a combination-therapy group. Single-cell RNA sequencing was used to characterize immune cell subtypes and tumor-immune crosstalk, immunofluorescence staining was performed on tumor tissue, and a co-culture model of CD8+ T cells and multiple myeloma cell lines was established to confirm the mechanism behind the combination’s antitumor effect.

Key Findings:

Selinexor treatment was found to upregulate CD73 expression in the majority of tumors, a resistance-associated mechanism that the combination approach was designed to counter. In the mouse model, the combination therapy suppressed tumor growth with an inhibition rate of 62%, compared with 31% for ATG-037 monotherapy and 43% for selinexor monotherapy. Single-cell RNA sequencing showed that the combination synergistically potentiated CD8+ T cell activation by enhancing the interaction between CD8+ T cells and Enpp1+ cells via the CD80–CD28 signaling pathway, and the resulting increase in CD8+ T cell infiltration into tumor tissue was confirmed by immunofluorescence staining. In co-culture experiments, CD73 inhibition was shown to strengthen selinexor-mediated tumor cell killing by activating CD8+ T cells, with significantly elevated levels of Granzyme B (P=0.0252) and IFN-γ (P=0.0067) observed in the combination group.

Conclusion:

The study highlights the synergistic potential of combining selinexor with a CD73 inhibitor for enhancing CD8+ T cell-mediated tumor cytotoxicity in MM. Selinexor therapy upregulates CD73 in the TME, driving adenosine accumulation and an immunosuppressive state. Combined use of ATG-037 blocks this immunosuppressive feedback loop via suppression of CD73-dependent adenosine synthesis, restoring CD8+ T cell activation and proliferation while enhancing T cell cytotoxicity through activation of the CD80-CD28 costimulatory axis. These findings establish a novel, clinically feasible therapeutic paradigm for addressing drug resistance and refractory MM.

(Press release, Antengene, SEP 14, 2026, View Source [SID1234670783])

On September 14, 2026 Telix reported that the United States (U.S.) Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for Pixclara (floretyrosine F 18 or 18F-FET), an amino acid positron emission tomography (PET) drug for imaging gliomas (brain cancer).

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Pixclara is a radioactive diagnostic drug indicated for use with positron emission tomography (PET) to differentiate recurrent or progressive glioma from treatment-related change, in conjunction with other diagnostic evaluations, in adults and pediatric patients 1 month of age and older.

PET imaging with floretyrosine F 18 (FET-PET) is recommended in international clinical practice guidelines for the imaging of gliomas, including NCCN Guidelines[1], but until now there has not been an FDA-approved product available in the U.S.

Gliomas are the most common form of central nervous system (CNS) cancer, accounting for approximately 30% of all brain and CNS tumors and 80% of all malignant brain tumors[2]. In the U.S., approximately 24,000 new glioma cases are diagnosed each year[3], representing a significant unmet addressable need.

Kevin Richardson, Chief Executive Officer, Telix Precision Medicine, said, "FDA approval of Pixclara will enable broad access in the U.S. to FET-PET imaging, which is already recognized in international clinical practice guidelines. As the first FDA-approved PET imaging drug for glioma, Pixclara will provide physicians in the U.S. with more certainty in their diagnoses and greater confidence in their treatment planning for patients."

Kelly Sitkin, President and CEO, American Brain Tumor Association, said, "The approval of Pixclara will advance glioma care by enabling more precise monitoring, complementing the role of MRI. We welcome the FDA’s decision, which provides a pathway to access this technology in the U.S. and helps address a critical unmet need in brain cancer diagnostics."

Patrick Wen, MD, E. Antonio Chiocca, MD, PhD, Family Endowed Chair in Neuro-Oncology at Mass General Brigham Cancer Institute, said, "Having an FDA-approved FET-PET product with high diagnostic accuracy will make a significant, positive difference to the management of patients with gliomas. This is a very positive step forward for brain cancer imaging and treatment planning."

About Pixclara (floretyrosine F 18)

Pixclara is an intravenous positron emission tomography (PET) imaging drug for the differentiation of recurrent or progressive glioma from treatment-related change, in conjunction with other diagnostic evaluations, in adults and pediatric patients 1 month of age and older. It comprises a small molecule targeting compound labeled with a diagnostic radioisotope, fluorine-18. After administration into the bloodstream, Pixclara targets membrane transport proteins known as L-type amino acid transporters 1 and 2 (LAT1 and LAT2). Once bound, energy emissions from the radioisotope can be detected by a PET scanner. Pixclara (TLX101-Px) is also the subject of a Phase 3 registrational study for potential indication expansion for the diagnosis of brain metastases[4].

Pixclara is the only FDA-approved radiopharmaceutical imaging drug for glioma (brain cancer).

INDICATIONS AND USAGE
PIXCLARA is indicated for use with positron emission tomography (PET) to differentiate recurrent or progressive glioma from treatment-related change, in conjunction with other diagnostic evaluations, in adults and pediatric patients 1 month of age and older.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
Risk for Misinterpretation
Image misinterpretation may occur with PIXCLARA PET. A negative image does not rule out the presence of recurrent or progressive glioma and a positive image does not confirm the presence of recurrent or progressive glioma. Equivocal findings may occur with PIXCLARA PET, including low-level or atypical uptake patterns, which may result in false positive or false negative interpretations.

Interpret PIXCLARA PET findings with caution and correlate results with available clinical evaluations, such as histopathology, cross-sectional imaging, and/or clinical history to support appropriate clinical decision-making.

Radiation Risks
PIXCLARA contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe drug handling to protect patients and health care providers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration.

ADVERSE REACTIONS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of PIXCLARA was evaluated in 382 patients with gliomas. Among these 382 patients, 371 adult patients received at least one intravenous dose of PIXCLARA at a mean activity of 204 ± 18 MBq (5.5 ± 0.47 mCi). The remaining 11 pediatric patients received at least one intravenous dose of PIXCLARA at a mean activity of 155 ± 53.5 MBq (4.2 ± 1.4 mCi).

The mean age of the patients was 57 years (range: 5 years to 86 years). Sex was 59% male, 37% female, and 3% unreported. Distribution by race was 26% White, 6% Asian, <1% Black or African American, and 67% other or unreported. Distribution by ethnicity was 3% Hispanic/Latino, 96% non-Hispanic/Latino, and <1% unknown or unreported.

Adverse reactions that occurred in ≥0.5% of patients receiving PIXCLARA were headache (0.5%).

Adverse reactions that occurred in <0.5% of patients were nausea, injection site reaction, fatigue, and malaise.

Adverse Reactions in Pediatric Patients
Overall, the safety profile observed in pediatric patients from the clinical study was consistent with the safety profile in adult patients.

(Press release, Telix Pharmaceuticals, SEP 14, 2026, View Source [SID1234670776])

On September 14, 2026 Astrazeneca reported updated exploratory results from the ADAURA Phase III trial showed Tagrisso (osimertinib) demonstrated a sustained, clinically meaningful overall survival (OS) benefit at eight years compared to placebo in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent.

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These results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, Republic of Korea (Abstract PL03.01). These data were also simultaneously published in the Journal of Thoracic Oncology.

At eight years of follow-up, results showed that Tagrisso continued to show an OS benefit, reducing the risk of death compared to placebo by 47% in the primary population (Stages II-IIIA) (based on a hazard ratio [HR] of 0.53; 95% confidence interval [CI] 0.38-0.75). In the overall trial population (Stages IB-IIIA), Tagrisso reduced the risk of death compared to placebo by 48% (HR 0.52; 95% CI 0.39-0.71). An estimated 74% of patients treated with Tagrisso were alive at eight years versus 58% of those treated with placebo in the primary population. In the overall trial population, an estimated 79% of patients treated with Tagrisso were alive at eight years versus 64% of those treated with placebo. Consistent with the planned final analysis, OS benefit with Tagrisso versus placebo was observed across all predefined subgroups.

Roy S. Herbst, MD, PhD, Director at Dartmouth Cancer Center, and principal investigator in the ADAURA Phase III trial, said: "These ADAURA findings show patients continue to experience meaningful, long-term benefit following early intervention with adjuvant osimertinib, with a 16 per cent point improvement in overall survival at eight years versus placebo. This is especially impressive given high rates of crossover to osimertinib following disease recurrence. This durable overall survival benefit reinforces the importance of prioritising EGFR testing at diagnosis so as many patients as possible can benefit from this transformative therapy."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "ADAURA continues to set new benchmarks in early-stage EGFR-mutated lung cancer, with nearly 80 per cent of patients treated with adjuvant Tagrisso alive at eight years. These results underscore the importance of treating early and reinforce Tagrisso as the adjuvant standard of care and backbone therapy across stages of the disease."

Summary of updated OS results: ADAURAi,ii

Tagrisso
Placebo
Stages II-IIIA (primary population)
(n=233)
(n=237)
Median duration of follow-up, in months
92
68.5
OS HR (95% CI)
0.53 (0.38, 0.75)
OS rate at 96 months (95% CI), %
74 (67, 80)
58 (50, 65)
Stage IB-IIIA (overall population)
(n=339)
(n=343)
Median duration of follow-up, in months
93.3
79.6
OS HR (95% CI)
0.52 (0.39, 0.71)
OS rate at 96 months (95% CI), %
79 (74, 83)
64 (58, 70)
i The updated analysis data cut-off (DCO) date was May 4, 2026.
ii This exploratory long-term OS analysis was conducted in all randomised patients. 127 patients did not have additional survival data and remained censored, with survival time unchanged from the planned final OS analysis until 4 May 2026.
Final safety data for ADAURA were collected at the planned final OS analysis, at which time the safety and tolerability of Tagrisso were consistent with its established profile with no new safety concerns.

Complementing the ADAURA clinical trial findings, real-world evidence presented at WCLC26 from a retrospective cohort study of US patients with early-stage (I-IIIA) EGFRm NSCLC (Abstract P1.142) showed that early discontinuation of Tagrisso before completion of the three-year treatment course more than doubled the risk of disease recurrence or death. These results reinforce the importance of maintaining the full treatment duration established in ADAURA and underscore the need for clinician-patient communication to support treatment persistence.

In the advanced disease setting, additional data presented at WCLC26 from the FLAURA2 Phase III trial reinforced the benefits of backbone therapy Tagrisso in combination with platinum-pemetrexed chemotherapy in patients with 1st-line advanced EGFRm NSCLC. Results from a novel safety analysis (Abstract PT2.03.03) showed that with long-term follow-up (median 42.6 months), the safety and tolerability of Tagrisso plus platinum–pemetrexed remained consistent with the established safety profiles of these medicines, with clear reductions in new adverse event onset following the initial induction period. Additionally, an exploratory analysis (Abstract P2.237) showed that progression-free survival and OS HRs numerically favoured Tagrisso plus platinum–pemetrexed versus Tagrisso monotherapy regardless of baseline TP53 co-mutation status.

Notes
NSCLC
Lung cancer is the leading cause of cancer death globally, accounting for almost one in five (19%) cancer deaths.1-2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.3 Approximately 75% of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.4-5 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.6

For patients with resectable tumours, the majority eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.7 Further, 73% of patients with Stage IB and 56-65% of patients with Stage II disease will survive for five years. This decreases to 41% for patients with Stage IIIA.8

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signalling pathways that drive the growth of tumour cells.12

ADAURA
ADAURA was a randomised, double-blind, placebo-controlled, global Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumour resection and, at physicians’ and patients’ discretion, adjuvant chemotherapy. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial was enrolled in more than 200 centres across more than 20 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was disease-free survival (DFS) in Stage II and IIIA patients and key secondary endpoints included DFS in Stage IB, II and IIIA patients, and OS in both the primary and overall populations.

The exploratory analysis presented at WCLC26 was conducted in all randomised patients including complete or partial extended long-term survival data from approximately 77% of those patients who were still alive at the final planned OS analysis DCO. This included trial participants with additional survival data up until the 4 May 2026 DCO or from accessible medical records/information from last contact date. 127 patients did not have additional survival data and remained censored, with survival time unchanged from the planned final OS analysis until 4 May 2026.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

Tagrisso is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. Tagrisso is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, Tagrisso demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. Tagrisso is also being investigated in this setting in combination with Orpathys (savolitinib) in the SAFFRON Phase III trial and in combination with Datroway (datopotamab deruxtecan) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

In addition to ADAURA, Tagrisso also showed improved outcomes in early-stage disease in the NeoADAURA Phase III trial and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

(Press release, AstraZeneca, SEP 14, 2026, View Source [SID1234670775])

On September 14, 2026 AstraZeneca and Daiichi Sankyo reported that positive results from the DESTINY-Lung04 Phase III 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 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).

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Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).

In the primary endpoint of PFS, 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 with Enhertu compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favourable PFS trend was seen for Enhertu across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.

Objective response rate (ORR) with Enhertu was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for Enhertu was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.

Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: "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. With seventy per cent 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."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "DESTINY-Lung04 is the first Phase III 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. 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."

John Tsai, Global Head, R&D, Daiichi Sankyo, said: "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. 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."

Summary of results: DESTINY-Lung04i

Efficacy measure
Enhertu
(5.4mg/kg; n=227)
Pembrolizumab plus chemotherapy
(n=227)
PFSii
Median PFS, (months) (95% CI)
14.3
(12.4-16.5)
8.3
(7.0-9.9)
Hazard ratio (95% CI)
HR 0.63 (0.50-0.79)
p-value
p<0.0001
ORRii,iii
ORR% (n)
(95% CI)iv
70.0% (159)
(63.6-75.9)
44.5% (101)
(37.9-51.2)
CR, % (n)
1.8% (4)
1.8% (4)
PR, % (n)
68.3% (155)
42.7% (97)
Median DOR, (months) (95% CI)
13.4
(10.4-17.2)
9.7
(7.0-11.1)
PFS2iii,v
Median PFS2, (months) (95% CI)
22.7
(20.3-26.3)
17.3
(15.6-21.8)
Hazard ratio (95% CI)
HR 0.80 (0.62-1.02)
OSvi
Median OS, (months) (95% CI)
29.3
(26.2-33.4)
33.1
(27.7-40.7)
Hazard ratio (95% CI)
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
i Analysis was based on a data cut-off (DCO) of 9 June 2026; median duration of follow-up was 21.6 in the Enhertu arm and 20.4 months in the pembrolizumab plus chemotherapy arm. At DCO, 40 patients (17.7%) remained in the Enhertu arm and 10 patients (4.5%) in the pembrolizumab plus chemotherapy arm.
ii Assessed by BICR
iii Assessed by investigator
iv ORR is (CR + PR); includes unconfirmed responses
v PFS2 is defined as the time from randomisation to second progression (earliest progression event following first subsequent therapy) or death
vi At DCO, overall data maturity for OS was 46.9% and no formal hypothesis testing was performed; formal hypothesis testing will be performed at the second interim analysis and final analysis
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% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the Enhertu arm (23.8%).

The safety profile of Enhertu observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.

Despite longer treatment exposure in the Enhertu arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between Enhertu and pembrolizumab plus chemotherapy (34.1% in the Enhertu arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the Enhertu arm and 14.1% in the pembrolizumab plus chemotherapy arm). 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 Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the Enhertu arm.

Enhertu is approved to treat patients with previously treated metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumours, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Notes

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.3-5

HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumour types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2-4% of patients with non-squamous NSCLC.6-9 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, 10-14

The global standard of care in the 1st-line metastatic setting of patients with HER2-mutant NSCLC is a combination of immunotherapy and doublet platinum-based chemotherapy.15-17 However, many patients do not respond to 1st-line treatment and experience disease progression, underscoring the need for additional treatment options.18

DESTINY-Lung04
DESTINY-Lung04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/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 harbouring a HER2 exon 19 or 20 mutation.

Patients were randomised 1:1 to receive either Enhertu or standard of care. Randomisation 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 ORR and DOR assessed by BICR and investigator, PFS2 by investigator, OS, 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.

Enhertu
Enhertu 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 programme 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 (5.4mg/kg) followed by THP is approved in the approved in the US, China, India, Singapore, Brazil and Taiwan 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 (5.4mg/kg) is approved in the US, Brazil, India and Canada 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 (5.4mg/kg) in combination with pertuzumab is approved in more than 40 countries worldwide as a 1st-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 (5.4mg/kg) is approved in more than 100 countries 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 (5.4mg/kg) is approved in more than 75 countries 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 (5.4mg/kg) is approved in more than 100 countries 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 (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours 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 US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 90 countries 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 (5.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours 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 US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu clinical development programme
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, AstraZeneca, SEP 14, 2026, View Source [SID1234670774])