1stOncology™: Cancer Intelligence Service – Page 577 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Nuvalent Presents Pivotal Data from ARROS-1 Clinical Trial of Zidesamtinib for TKI Pre-treated Patients with Advanced ROS1-positive NSCLC at WCLC 2025

On September 7, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported pivotal data for zidesamtinib, a novel investigational ROS1-selective inhibitor, in TKI (tyrosine kinase inhibitor) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from its global ARROS-1 Phase 1/2 clinical trial as part of the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer (WCLC 2025), being held in Barcelona, Spain (Press release, Nuvalent, SEP 7, 2025, View Source [SID1234655805]). The presentation slides will be available on the Nuvalent website at www.nuvalent.com following the Presidential Symposium.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The pivotal data presented today, initially announced in June 2025, serve as the foundation for the company’s ongoing rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for zidesamtinib in TKI pre-treated patients with advanced ROS1-positive NSCLC. The FDA agreed to accept the NDA for participation in the Real-Time Oncology Review (RTOR) program, which facilitates earlier submission of topline efficacy and safety results prior to the submission of the complete application, to support an earlier start to the FDA’s evaluation of the application. The company is on track to complete its rolling NDA submission in the third quarter of 2025, and continues to engage with the FDA on potential opportunities for line-agnostic expansion.

"There remains a clear need for new treatment options for patients with ROS1-positive NSCLC, particularly those who are unable to tolerate the currently available TKIs, and those whose disease progresses with brain metastases or resistance mutations," said Christopher Turner, M.D., Chief Medical Officer at Nuvalent. "We are encouraged by the data presented today, which we believe highlight the potential of zidesamtinib to deliver meaningful outcomes with a generally safe and well-tolerated safety profile. These data represent important progress toward our goal of offering a new standard of care for this patient community. Congratulations to the entire Nuvalent team and our collaborators for the achievement of this important milestone."

About Zidesamtinib and the ARROS-1 Phase 1/2 Clinical Trial

Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC.

Zidesamtinib is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. The completed Phase 1 portion enrolled ROS1-positive NSCLC patients who previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors who had been previously treated. The Phase 1 portion of the trial was designed to evaluate the overall safety and tolerability of zidesamtinib, with additional objectives including determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and evaluation of preliminary anti-tumor activity. The ongoing global, single arm, open label Phase 2 portion is designed with registrational intent for TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC.

Ivonescimab Plus Chemotherapy Demonstrates Consistent Global Benefit: HARMONi Data Update Shows OS HR=0.78, Nominal P=0.0332

On September 7, 2025 Akeso, Inc. (HKEX: 9926.HK) reported that its global partner, Summit Therapeutics Inc. (NASDAQ: SMMT), announced the updated overall survival (OS) results from the global Phase III HARMONi clinical trial of ivonescimab, a novel PD-1/VEGF bispecific antibody, at the Presidential Symposium in the 2025 World Conference on Lung Cancer (WCLC) (Press release, Akeso Biopharma, SEP 7, 2025, View Source;nominal-p0-0332–302548481.html [SID1234655804]).

Longer-term follow-up of western patients showed improving, favorable trend in OS, yielding a hazard ratio (HR) of 0.78 and a nominal p-value of 0.0332.

Meanwhile, Akeso recently announced that the HARMONi-A study conducted in China has also recently reached the OS clinical endpoint, achieving clinically meaningful and statistically significant OS benefit. The OS data from this study will be presented at upcoming academic conferences.

The results from the first international multi-center Phase III HARMONi study of ivonescimab, along with those from the Phase III HARMONi-A study conducted in China, demonstrated consistent and robust clinical efficacy in both progression-free survival (PFS) and OS. These findings provide strong evidence that ivonescimab not only offers significant advantages in terms of rapid onset of action and effective disease control in cancer treatments but also provide survival benefits to patients. The data further support ivonescimab’s consistent efficacy and safety across diverse global populations, including both international and Chinese cohorts, reinforcing its potential for broad therapeutic benefit for cancer patients worldwide.

Approximately 38% of patients were recruited from western countries.

The trial results were presented by Jonathan Goldman, MD, Professor of Medicine at UCLA in the Hematology/Oncology Division, UCLA Director of Clinical Trials in Thoracic Oncology, Associate Director of Early Drug Development, and Chair of University of California Lung Cancer Consortium.

Clinically Meaningful Efficacy

As previously disclosed, ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057). The statistical analysis plan for the study required a p-value of 0.0448 in order to achieve statistical significance at the time of the primary analysis of overall survival. Median overall survival was 16.8 months for those patients administered ivonescimab plus chemotherapy vs. 14.0 months for those receiving placebo plus chemotherapy. It was noted at the time of the primary analysis that the median follow-up time for western patients was 9.2 months and less than the median overall survival at the time of the primary analysis, and these patients may continue to be followed for long-term outcomes.

In September 2025, an additional analysis was performed, whereby the western patients were followed to increase their time on study (Asian patients were locked at the time of the primary analysis). In this analysis that included longer-term follow-up of western patients (median follow-up time of western patients of 13.7 months), a hazard ratio consistent with the primary analysis was observed with an improved nominal p-value (HR=0.78; 95% CI: 0.62 – 0.98; nominal p=0.0332). Median OS for this analysis remained the same in both arms from the primary analysis. Median OS in western patients receiving ivonescimab was 17.0 months compared to 14.0 months for those receiving placebo (HR=0.84); median OS in North American patients, specifically, had not yet been reached in the ivonescimab arm compared to 14.0 months in the placebo arm (HR=0.70). The hazard ratios for western patients in totality, as well as patients from the North American and European regions individually, improved from the primary OS analysis to the analysis with longer-term follow-up of western patients. Consistent benefit was observed across pre-defined subgroups.

As previously disclosed at the prespecified primary data analysis for PFS, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p<0.00001). PFS was measured by blinded independent central radiology review committee (BICR) compared to placebo in combination with chemotherapy. Median PFS for ivonescimab vs. placebo plus chemotherapy was 6.8 months vs. 4.4 months, respectively. The PFS analysis was event driven and was conducted with 345 patients enrolled. There was a consistent observed benefit across pre-defined subgroups.

In a longer-term follow-up of PFS, which included all western patients and at least six months of follow-up time for all patients, ivonescimab plus chemotherapy demonstrated a consistent, clinically meaningful improvement in PFS with an observed HR of 0.57 (95% CI: 0.46 – 0.71). With the longer-term follow-up analysis, a consistent benefit in western vs. Asian patients was observed, as well as in patients with tumors with either PD-L1 positive or negative expression. This longer-term follow-up analysis of PFS was performed at the time of the primary OS analysis.

Overall response rates were higher in the ivonescimab arm (45%) vs. the placebo arm (34%); median duration of response was longer in those patients administered ivonescimab plus chemotherapy (7.6 months) compared to those receiving placebo and chemotherapy (4.2 months)

Ivonescimab demonstrated a favorable safety and tolerability profile with no new safety signals identified. The safety results from the HARMONi study were consistent with those observed in the HARMONi-A trial.

Ivonescimab has shown positive results in the HARMONi-2 trial, a randomized, double-blind, head-to-head Phase III study against pembrolizumab monotherapy, which led to its approval for first-line treatment of PD-L1-positive NSCLC (its second approved indication). Besides that, ivonescimab plus chemotherapy has now also demonstrated significant positive outcomes in another head-to-head Phase III study against tislelizumab plus chemotherapy in first-line squamous NSCLC. This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared to PD-1 in combination with chemotherapy (the optimal standard of care for many cancer treatments), or compared to VEGF-related therapies in the area of anti-angiogenesis. This highlights the remarkable capability of ivonescimab to make leapfrog advancements in cancer treatment.

Ivonescimab continues to validate its clinically meaningful profile and potential with a strategically expanded development program targeting key immuno-oncology settings:

Phase III trials for Lung cancer (8 registrational/Phase III trials, 4 already met primary endpoints):

First-line NSCLC, squamous and non-squamous (versus pembrolizumab + chemotherapy; global trial)
First-line squamous NSCLC (versus tislelizumab + chemotherapy)
NSCLC after progression on EGFR-TKI therapy (HARMONi-A and HARMONi studies)
First-line PD-L1-positive NSCLC (versus pembrolizumab monotherapy)
First-line PD-L1-high expressing NSCLC (versus pembrolizumab)
IO-resistant NSCLC
Consolidation therapy for limited-stage small cell lung cancer (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT)
Phase III trials for core immuno-oncology indications (first-line therapy):

First-line biliary tract cancer (versus durvalumab + chemotherapy)
First-line PD-L1-positive head and neck squamous cell carcinoma (HNSCC) in combination with ligufalimab (anti-CD47) versus pembrolizumab
Phase III trials for cold tumors and more：

First-line triple-negative breast cancer (TNBC)
First-line MSS/pMMR colorectal cancer (representing about 95% of CRC cases)
First-line pancreatic cancer
Additional global Phase III trials are in advanced stages of planning
An extensive clinical foundation includes over 20 Phase II studies across more than 10 additional tumor types, generating compelling efficacy and safety data to enable rapid transition to further registrational studies worldwide.

Ivonescimab uniquely targets both PD-1 and VEGF, producing a synergistic anti-tumor effect. This dual mechanism not only combines the benefits of PD-1 and VEGF inhibition but also overcomes the efficacy and safety limitations of each target alone, resulting in pronounced clinical benefits. These advantages have been confirmed across multiple Phase III trials and real-world use, rapidly establishing ivonescimab as a next-generation leader in immunotherapy and anti-angiogenic therapy.

Akeso is implementing a dual-path strategy to maximize the value of ivonescimab world wide: accelerating domestic commercialization and label expansion in China, while simultaneously advancing global development in partnership with Summit Therapeutics.

Forward-Looking Statement of Akeso, Inc.

This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso’s management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso’s other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in P.R.China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Akeso’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.

IDEAYA Biosciences and Hengrui Pharma Present Positive Phase 1 Data for IDE849 (SHR-4849), a Potential First-in-Class DLL3 TOP1 ADC, in Small Cell Lung Cancer at the IASLC 2025 World Conference on Lung Cancer

On September 7, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, and Hengrui Pharma, a global pharmaceutical company focused on scientific and technological innovation, reported initial data from Hengrui’s Phase 1 clinical trial of IDE849 (SHR-4849), a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topoisomerase-1 (TOP1) antibody drug conjugate (ADC), in an oral presentation today at the IASLC 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain (Press release, Ideaya Biosciences, SEP 7, 2025, View Source [SID1234655803]). The presentation included data from a total of 100 patients who received IDE849 at doses between 0.8 mg/kg to 4.2 mg/kg with a once every 3-week dosing interval.

"We believe the ORR, median PFS, and overall safety data presented at WCLC 2025 in over 70 efficacy evaluable SCLC patients provides a potential best-in-class DLL3 TOP1 ADC profile," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "We look forward to advancing the global clinical development of IDE849 in SCLC, NETs, and additional DLL3 upregulated solid tumors, as both a potential first-in-class and best-in-class DLL3 TOP1 ADC to address areas of high unmet medical need in cancer."

Data in the presentation were as of a cut-off date of June 20, 2025, and included 87 patients with small-cell lung cancer (SCLC) and 13 patients with other neuroendocrine carcinomas (NEC). All patients had progressed after front-line therapy, with 33% having progressed after two prior lines and 15% after three or more prior lines of therapy. Of the 87 SCLC patients enrolled, 72.4% (63/87) had received prior immunotherapy. A total of 71 patients with refractory SCLC (2L+) were evaluated for initial efficacy at doses of 2.4 mg/kg (n=19), 3.0 mg/kg (n=18) and 3.5 mg/kg (n=31) in the expansion phase of the trial. Patients in the 4.2 mg/kg cohort (n=3) of the dose escalation phase were also included in the analysis. All efficacy-evaluable patients had received at least one post-baseline tumor assessment per RECIST v1.1.

Key data highlights from the presentation

Efficacy (n=71 evaluable SCLC patients treated with IDE849)

IDE849 Dose Level

2.4 mg/kg

Total (≥2.4 mg/kg)

Treatment setting
(# patients)

2L
(n=10)

All-lines
(n=19)

2L
(n=35)

All-lines
(n=71)

ORR (%, n)

80.0% (8/10)

73.7% (14/19)

77.1% (27/35)

73.2% (52/71)

Confirmed ORR (%, n)

70.0% (7/10)

57.9% (11/19)

60.0% (21/35)

47.9% (34/71)

Pending confirmation

—

5.3% (1/19)

11.4% (4/35)

14.1% (10/71)

DCR

100% (10/10)

94.7% (18/19)

97.1% (34/35)

93.0% (66/71)

Robust overall response rate (ORR) and disease control rate (DCR) were consistently observed across all expansion doses evaluated and in patients across all lines of therapy, with a modest reduction in ORR/DCR observed in later-line patients, consistent with their more advanced stage of disease.

14.1% (10/71) of patients across all doses >2.4 mg/kg are still pending confirmation, as well as multiple patients who have had limited follow-up (e.g. one post-baseline scan) highlighting the study has not yet achieved a fully mature confirmed ORR%.

In patients with baseline brain metastasis, a confirmed ORR of 83.3% (5/6) and a DCR of 100% (6/6) was observed at the 2.4 mg/kg dose. Across all doses ≥2.4 mg/kg (n=18) with baseline brain metastasis, the confirmed ORR was 66.7% (12/18) with a DCR of 100% (18/18). A confirmation scan for one unconfirmed partial response is pending, which if confirmed, would increase the confirmed ORR to 72.2% (13/18).

Median PFS was 6.7 months across all lines of treatment at doses of IDE849 ≥2.4 mg/kg (n=86); median PFS was not yet reached (NR) in 2L patients (n=42).

As of the cut-off date of June 20, 2025 the median length of follow-up was 3.5 months.
Safety (n=100 SCLC and NEC patients treated with IDE849)

Across all patients and all dose levels (n=100), Grade 3 or higher (Gr>3) treatment-related adverse events (TRAEs) occurred in 48% (48/100) and serious TRAEs in 16% (16/100) of patients. The most common TRAEs were white blood cell reduction (27% Gr>3), neutropenia (33% Gr>3), anemia (6% Gr>3) and nausea (0% Gr>3).

TRAEs leading to dose reduction in 15% (15/100) of patients; treatment-related discontinuation rate of 2% (2/100) with no treatment-related deaths reported.
IDEAYA will review the data that was presented by Hengrui at their 10-Year Anniversary R&D Day on September 8th in New York. A link to the oral presentation from WCLC will be available on the Investor Relations page of the IDEAYA corporate website: View Source

In December 2024, Hengrui Pharma granted IDEAYA an exclusive worldwide license to develop and commercialize SHR-4849 (IDE849) outside of Greater China. The partners will collaborate to accelerate global development of this innovative therapy for patients worldwide.

Tagrisso plus chemotherapy demonstrated a median overall survival of nearly four years, the longest benefit ever reported in a global Phase III trial in EGFR-mutated advanced lung cancer

On September 7, 2025 Astrazeneca reported positive results from the final overall survival (OS) analysis of the FLAURA2 Phase III trial showed AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS compared to Tagrisso monotherapy in the 1st-line treatment of patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, SEP 7, 2025, View Source [SID1234655802]).

These results will be presented today during the Presidential Symposium at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain (abstract #PL02.04).

In the final OS analysis, Tagrisso plus chemotherapy demonstrated a median OS of nearly four years (47.5 months) compared to approximately three years (37.6 months) for Tagrisso monotherapy. At 57% data maturity, results showed Tagrisso plus chemotherapy reduced the risk of death by 23% compared to Tagrisso monotherapy (based on a hazard ratio [HR] of 0.77; 95% confidence interval [CI] 0.61-0.96; p=0.0202). An estimated 63.1% of patients treated with the combination were alive at three years and 49.1% of patients were alive at four years compared to 50.9% and 40.8%, respectively, in the monotherapy arm. Importantly, the observed OS benefit for Tagrisso plus chemotherapy versus Tagrisso monotherapy was consistent across all prespecified subgroups. Patients in the control arm received standard of care, including chemotherapy, upon progression, supporting the relevance of the OS results.

David Planchard, MD, PhD, Thoracic Oncologist at Gustave Roussy Institute of Oncology, Villejuif, France, and principal investigator for the trial, said: "The fundamental goals of lung cancer treatment are to extend survival while preserving patients’ quality of life. These compelling results, which demonstrated unprecedented median overall survival, show this combination can achieve both of these goals and support osimertinib, with or without the addition of chemotherapy, as the standard of care for patients with 1st-line advanced EGFR-mutated lung cancer. With two highly effective osimertinib-based options for these patients, physicians can better tailor treatment to individual needs and help ensure the best possible outcome for each patient."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The latest FLAURA2 trial results set a new survival standard for patients, with Tagrisso plus chemotherapy demonstrating a median overall survival of nearly four years in 1st-line advanced EGFR-mutated lung cancer—surpassing the three-year benchmark established in the FLAURA trial. Over the past decade, Tagrisso has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung cancer, cementing its role as the backbone therapy in EGFR-mutated lung cancer."

Summary of OS results: FLAURA2

Tagrisso plus chemotherapy (n=279)

Tagrisso monotherapy (n=278)

Median OS (in months)i,ii, iii

47.5 (41.0-NCiv)

37.6 (33.2 ,43.2)

Hazard ratio (95% CI)

0.77 (0.61-0.96)

Stratified log-rank p-valuev

0.0202

Number of deaths, n (%)

144 (51.6)

171 (61.5)

Data maturity

57%

OS rate at 24 months (%)

79.7 (74.5-84.0)

71.5 (65.8-76.5)

OS rate at 36 months (%)

63.1 (57.1-68.5)

50.9 (44.8-56.6)

OS rate at 48 months (%)

49.1 (43.0-55.0)

40.8 (34.9-46.6)

i. OS data cut-off date was 12 June 2025
ii. Median follow-up duration for OS in censored patients at data cut-off: 51.2 (0.2-60.4) months for Tagrisso plus chemotherapy and 51.3 (0.1-60.1) months for Tagrisso monotherapy
iii. Calculated by Kaplan–Meier method
iv. Not calculable
v. For statistical significance, a 2-sided p-value of less than 0.04953, as determined by the O’Brien and Fleming spending rule, was required

With longer follow-up, the safety profile of Tagrisso plus chemotherapy continued to be manageable and consistent with the established profiles of the individual medicines. Grade 3 or higher adverse events (AEs) from all causes occurred in 70% of patients in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs, versus 34% in the Tagrisso monotherapy arm, similar to the rates reported at the primary analysis presented at the IASLC 2023 WCLC (64% versus 27%, respectively). Discontinuation rates due to AEs and on-target toxicities were low in both trial arms (12% versus 7%).

Notes

NSCLC
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases.1-2 Approximately 75% of people are diagnosed with advanced NSCLC.3 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.4-6

While EGFR-tyrosine kinase inhibitors (TKI) have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.7-10

FLAURA2
FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in previously untreated patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) NSCLC whose tumors have EGFR exon 19 deletion or exon 21 L858R mutations. Patients were treated with Tagrisso 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS with OS as the key secondary endpoint.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against 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 (CRT). 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 or Dato-DXd) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

Tagrisso also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials 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.

Ifinatamab Deruxtecan Demonstrated Clinically Meaningful Response Rates in Patients with Extensive-Stage Small Cell Lung Cancer in IDeate-Lung01 Phase 2 Trial

On September 7, 2025 Merck & Co. reported results from the IDeate-Lung01 Phase 2 trial showed ifinatamab deruxtecan (I-DXd) demonstrated clinically meaningful response rates in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) (Press release, Merck & Co, SEP 7, 2025, View Source [SID1234655801]). These data were presented today during a late-breaking presentation (OA06.03) and included as part of the press program at the 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC25).

Ifinatamab deruxtecan is a specifically engineered, potential first-in-class B7-H3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate. While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches.

In August 2025, ifinatamab deruxtecan was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.

Response was assessed in patients who received ifinatamab deruxtecan (12 mg/kg) in both the dose optimization and single-arm expansion parts of the trial. A confirmed objective response rate (ORR) of 48.2% (95% confidence interval [CI]: 39.6–56.9) was observed with ifinatamab deruxtecan in 137 patients with previously treated ES-SCLC as assessed by blinded independent central review (BICR). Three complete responses (CRs), 63 partial responses (PRs) and 54 cases of stable disease (SD) were seen. A median duration of response (DOR) of 5.3 months (95% CI: 4.0–6.5) and a disease control rate (DCR) of 87.6% (95% CI: 80.9–92.6) were observed. Median progression-free survival (PFS) was 4.9 months (95% CI: 4.2–5.5) and median overall survival (OS) was 10.3 months (95% CI: 9.1–13.3). Disease progression and time-to-event results support further randomized, controlled assessment.

In a subset of patients (n=32) receiving ifinatamab deruxtecan as a second-line treatment, a confirmed ORR of 56.3% (95% CI: 37.7–73.6) was observed as assessed by BICR. Eighteen PRs and 13 cases of SD were seen in this subset of patients. A median DOR of 7.2 months (95% CI: 3.6–NE) and a DCR of 96.9% (95% CI: 83.8–99.9) were observed. Median PFS of 5.6 months (95% CI: 3.9–8.1) and median OS of 12.0 months (95% CI: 7.3–19.1) were seen.

In a subset of patients (n=105) receiving ifinatamab deruxtecan in a third-line and beyond setting, a confirmed ORR of 45.7% (95% CI: 36.0–55.7) with three CRs, 45 PRs and 41 cases of SD were seen. A DCR of 84.8% (95% CI: 76.4–91.0) was observed in these patients.

In an exploratory analysis, an intracranial ORR of 46.2% (95% CI: 33.7–59.0) was observed by CNS RECIST v1.1 in a subset of patients (n=65) with brain metastases at baseline. A full subgroup analysis (2760MO) will be presented at 2025 European Society for Medical Oncology (#ESMO25).

"Patients with extensive-stage small cell lung cancer have an extremely poor prognosis despite current standard of care treatment options," said Myung-Ju Ahn, MD, PhD, Professor, Department of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. "The impressive response rates observed in IDeate-Lung01 provide further evidence of the potential role that ifinatamab deruxtecan could play in treating this aggressive form of lung cancer."

The safety profile observed in IDeate-Lung01 was consistent with that seen for ifinatamab deruxtecan in the Phase 1 trial with no new safety signals identified. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 36.5% of patients. The most common (>10%) grade 3 or higher TRAEs were neutropenia (13.9%), lymphopenia (12.4%), and anemia (10.2%). Seventeen patients (12.4%) had confirmed treatment-related interstitial lung disease (ILD)/pneumonitis as determined by an independent adjudication committee. The majority of ILD/pneumonitis events were low grade, with 11 grade 1 or 2 (8.0%), four grade 3 (2.9%), and two grade 5 (1.5%) ILD/pneumonitis events observed as of the data cutoff of March 3, 2025.

"In these primary results from IDeate-Lung01, ifinatamab deruxtecan produced clinically meaningful responses in patients with previously treated extensive-stage small cell lung cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "These data reinforce the potential benefit of this B7-H3 directed antibody drug conjugate in patients who have received one or more lines of platinum-based chemotherapy and will support our ongoing discussions with global regulatory authorities."

"Small cell lung cancer is the second most common type of lung cancer globally, with 15 percent of patients impacted by this particularly devastating form of the disease," said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. "With limited advances over the last 30 years, there is a high unmet need for new medicines and novel mechanisms of action that could provide additional options to patients with extensive-stage small cell lung cancer."

A majority of patients (54.7%) in IDeate-Lung01 received a median of two prior lines of treatment, including immunotherapy (81%), topoisomerase I inhibitor (32.1%), lurbinectedin (21.2%), amrubicin (8.8%) and DLL3-targeting T-cell engager (8.0%). As of the data cutoff, the median treatment duration was 4.8 months (range: 0.7–22.7) and 14 patients remain on treatment.

Efficacy Measure Ifinatamab Deruxtecan 12 mg/kg
Total Population (N=137) Second-Line Subset (n=32) Third-Line Plus and Beyond Subset (n=105)
Confirmed ORR, % (95% CI) 48.2% (39.6–56.9) 56.3% (37.7–73.6) 45.7% (36.0–55.7)
CR, n (%) 3 (2.2%) 0 3 (2.9%)
PR, n (%) 63 (46.0%) 18 (56.3%) 45 (42.9%)
SD, n (%) 54 (39.4%) 13 (40.6%) 41 (39.0%)
DCR (95% CI), % 87.6% (80.9–92.6) 96.9% (83.8–99.9) 84.8% (76.4–91.0)
DOR, median (95% CI), months 5.3 months (4.0–6.5) 7.2 months (3.6–NE) 4.3 months (3.7–5.8)
TTR, median (95% CI), months 1.4 months (1.0–8.1) 1.4 months (1.2–4.0) N/A
PFS, median (95% CI), months 4.9 months (4.2-5.5) 5.6 months (3.9–8.1) N/A
OS, median (95% CI), months 10.3 months (9.1-13.3) 12.0 months (7.3–19.1) N/A
CR, complete response; DCR, disease control rate; DOR, duration of response; N/A, not available; NE, not evaluable; ORR, objective response rate; OS, overall survival; PR, partial response; PFS, progression-free survival; SD, stable disease; TTR, time to response
About IDeate-Lung01

IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part Phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. Patients with asymptomatic brain metastases (untreated or previously treated) were eligible to participate.

In the first part of the trial (dose optimization), patients were randomized 1:1 to receive ifinatamab deruxtecan (8 or 12 mg/kg) given intravenously once every three weeks. In the second part of the trial (dose expansion), patients received ifinatamab deruxtecan (12 mg/kg) intravenously at the same dosing interval.

The primary endpoint is ORR as assessed by BICR per RECIST v1.1. Secondary endpoints included DOR, PFS, DCR, TTR, OS, pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis.

IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

About small cell lung cancer

More than 2.48 million lung cancer cases were diagnosed globally in 2022. Small cell lung cancer (SCLC) is the second most common type of lung cancer, accounting for approximately 15% of cases. SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate. While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches.

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including SCLC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer.

About ifinatamab deruxtecan

Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with extensive-stage SCLC with disease progression on or after platinum-based chemotherapy.

Ifinatamab deruxtecan has been granted orphan drug designation by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of SCLC.

About the ifinatamab deruxtecan clinical development program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan monotherapy and in combination with other cancer medicines across multiple cancers.