On October 18, 2025 EORTC reported that final results from CATNON trial show that the addition of 12 cycles of chemotherapy to radiotherapy can improve overall survival in a group of patients with a particular type of the rare brain tumour anaplastic glioma. The data will be presented today [Saturday] at the 20th Meeting of the European Association of Neuro-Oncology (EANO) by the study’s principal investigator, Dr Martin van den Bent, from the Erasmus MC Cancer Centre, Rotterdam, The Netherlands.

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The results show that, after a median follow up of nearly 11 years, the addition of 12 cycles of the chemotherapy agent temozolomide (TMZ) to radiotherapy in patients with an anaplastic astrocytoma improved overall survival in the subset of patients with a tumour that had a mutation in the IDH gene (IDHmt). The median overall survival in IDHmt patients who received TMZ after RT was around 12 years.

There was no observable benefit when TMZ chemotherapy was given during radiotherapy, nor in patients in which the tumour did not show an IDH mutation. Several biological markers were associated with outcome in patients with an IDH mutated glioma but, importantly, benefit from the treatment was still observed regardless of those markers.

The study was carried out by researchers from ten countries worldwide, and randomised 751 adult patients with newly diagnosed anaplastic glioma to radiotherapy alone, radiotherapy with concurrent TMZ, radiotherapy with TMZ given after treatment (adjuvant therapy), and radiotherapy with both concurrent and adjuvant TMZ. The patients were enrolled in the trial between 2007 and 2015.

The researchers found that adjuvant (post-radiation) TMZ significantly extended survival. The study confirms the importance of distinguishing between patients with tumours with an IDH mutation and those without. In patients whose tumours had the IDH mutation, the median survival increased to 12.5 years compared with six years in the control group who were initially treated with radiotherapy only. There was no benefit to patients who had concurrent TMZ if they also received an adjuvant treatment, regardless of the IDH status of the tumour.

Methylation profiling, a technique that allows the precise detection of specific regions of DNA, helped predict patient prognosis but did not affect their response to TMZ. This suggests that the chemotherapy benefits most risk groups, the researchers say. The use of methylation profiling to identify DNA modifications showed that more aggressive tumours had significantly worse outcomes, but all patients with IDH-mutant tumours benefited from the standard treatment.

This combined treatment should become the standard of care for patients with anaplastic astrocytoma with an IDH mutation, according to the researchers. This was underlined by the EANO Scientific Committee with its award of the Best Oral Presentation for Clinical Research. Dr van den Bent said: "These results emphasise the importance of long-term follow-up. Thanks to the commitment of patients and the collaboration with partners worldwide, we have been able to identify the optimal treatment strategy that can extend life significantly in this patient population."

EORTC CEO Dr Denis Lacombe said: "Given the rarity of these tumours and the fact that the role of IDH in glioma was only discovered recently, it is a significant achievement to have delivered these results in a short time period, and further underlines the important role of academic clinical research in helping rare disease patients."

Presentation number: OS05.2.A Final clinical and molecular analysis of the EORTC randomized phase III intergroup CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma without 1p/19q codeletion.

(Press release, EORTC, OCT 18, 2025, View Source [SID1234656764])

On October 18, 2025 SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing next-generation immunotherapies for infectious diseases and their associated cancers, reported the presentation of first-in-human clinical data for SCG142 in an investigator-initiated Phase I trial (NCT06544720) in patients with recurrent or metastatic HPV-associated carcinomas. The poster will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany, on Saturday, 18 October 2025.

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This ongoing first-in-human trial evaluates the safety, tolerability and preliminary efficacy of SCG142, a novel human papillomavirus (HPV) E7-specific T-cell receptor-engineered T (TCR T) cell therapy armoured with a TGFβRII-41BB chimeric switch receptor. Eligible patients are HLA-A*02:01-positive with advanced HPV16- or HPV52-positive carcinomas who have progressed on or were intolerant to at least one prior systemic therapy. Key endpoints include safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. As of the data cut-off, tumor shrinkage was observed in all seven treated patients, resulting in a disease control rate (DCR) of 100%. Four of the seven patients (57%) achieved >30% tumor reduction, including two confirmed partial responses (PR) and two unconfirmed PRs. No dose-limiting toxicities or serious adverse events were reported. These preliminary findings support continued clinical development of SCG142.

"SCG142 is a novel and differentiated HPV-specific TCR T cell therapy with promising clinical activity." said Prof. Dr. Yang Li, Director of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University. "We’re excited that tumor shrinkage was observed in all seven treated patients and that SCG142 was well tolerated. These encouraging preliminary findings underscore the potential of SCG142 to provide new solutions for patients in a variety of HPV16 and HPV52 expressing cancers and support further evaluation in larger patient cohorts", she added.

SCG142 was isolated with GianTCRTM, SCG’s proprietary TCR screening platform with the ability to identify fully natural TCRs with high affinity and high avidity properties as well as potent antiviral and anti-tumor effects against infection-related solid tumors accompanied by a lower risk of off-target toxicity. "We are delighted that the excellent preclinical profile of our HPV-E7-specific TCR – including high avidity and dual functionality in both CD8+ and CD4+ T cells – has translated into clinical activity with SCG142" added Dr. Susanne Wilde, VP, Head of Preclinical Research of SCG Cell Therapy.

Besides SCG142, SCG is also advancing SCG101, a hepatitis B virus (HBV)-specific TCR T cell therapy for the treatment of HBV-related hepatocellular carcinoma (HCC).

(Press release, SCG Cell Therapy, OCT 18, 2025, View Source [SID1234656750])

On October 18, 2025 Astrazeneca reported positive results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) in the neoadjuvant setting (before surgery) demonstrated a statistically significant and clinically meaningful improvement in the pathologic complete response (pCR) rate. The trial compared Enhertu followed by THP with dose-dense doxorubicin and cyclophosphamide followed by THP (ddAC-THP) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment.

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In DESTINY-Breast11, Enhertu followed by THP resulted in a pCR rate of 67.3% compared with 56.3% for ddAC-THP, representing a pCR rate improvement of 11.2%. Improvement in pCR rates was observed across both hormone receptor (HR)-positive and HR-negative subgroups (HR-positive: 61.4% versus 52.3%; HR-negative: 83.1% versus 67.1%). Additionally, after surgery, 81.3% of patients who received neoadjuvant treatment in the Enhertu followed by THP arm had no or minimal residual invasive cancer (residual cancer burden [RCB] 0+I) detected in the resected breast or lymph node tissue compared to 69.1% of patients in the comparator arm.

The secondary endpoint of event-free survival (EFS) was not mature at the time of this analysis (4.5% maturity at data cutoff); however, an early analysis showed a trend favouring Enhertu followed by THP versus ddAC-THP (hazard ratio 0.56; 95% CI 0.26-1.17).

Nadia Harbeck, MD, PhD, Director of Breast Center, Cancer Department of OB&GYN and CCC Munich, LMU University Hospital, Germany and principal investigator for the trial, said: "For patients with early breast cancer who are at high risk of disease recurrence, using the most effective treatment option at the earliest opportunity is critical to prevent recurrence, optimise safety and improve the potential for cure. In the DESTINY-Breast11 trial, more than two thirds of patients had a pathologic complete response with trastuzumab deruxtecan followed by THP, suggesting a potential new standard of care in the neoadjuvant setting for patients with high-risk, HER2-positive early breast cancer."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The goal of treatment in the early breast cancer setting is to provide patients with the best possible chance for cure whilst optimising the tolerability of the treatment regimen. The impressive pathologic response rates and favourable safety profile seen with Enhertu followed by THP in DESTINY-Breast11 have the potential to transform treatment in the neoadjuvant setting and underscore the importance of bringing Enhertu into earlier stages of HER2-positive disease."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "While achieving a pathologic complete response in HER2-positive early-stage breast cancer is critical for reducing disease recurrence and improving long-term prognosis, approximately half of patients still show evidence of residual disease following surgery with currently available neoadjuvant treatment options. The results from DESTINY-Breast11 show that treatment with Enhertu followed by THP prior to surgery resulted in no evidence of residual invasive disease in two thirds of patients, illustrating the first treatment regimen in more than a decade to significantly improve outcomes in the earliest treatment setting for HER2-positive breast cancer."

Summary of Results: DESTINY-Breast11i,ii

Efficacy Measure

Enhertu (5.4 mg/kg; 4 cycles) followed by THP (4 cycles) (n=321)

ddAC (4 cycles) followed by THP (4 cycles)
(n=320)

pCR

pCR rate, %iii

67.3

56.3

ΔpCR,% (95% CI)iii,iv

11.2 (4.0-18.3)

p=0.003

HR-positive subgroup pCR rate, %iii

61.4

52.3

ΔpCR, % (95% CI)

9.1 (0.2-17.9)

HR-negative subgroup pCR rate, % iii

83.1

67.1

ΔpCR, % (95% CI)

16.1 (3.0-28.8)

RCB (0+I)v

RCB (0+I rate), %

81.3

69.1

ΔRCB, %

12.2

RCB-I rate, %

68.8

57.5

RCB-0 rate, %

12.5

11.6

HR-positive subgroup RCB (0+I) rate, %

78.0

64.7

ΔRCB, % (95% CI)

13.3

HR-positive RCB-I rate, %

63.1

52.8

HR-positive RCB-0 rate, %

14.8

11.9

HR-negative subgroup RCB (0+I) rate, %v

90.4

81.2

ΔpCR, % (95% CI)

9.2

HR-negative RCB-I rate, %

84.3

70.6

HR-negative RCB-0 rate, %

6.0

10.6

EFSvi

2-year EFS, %

Hazard ratio (95% CI)

96.9

93.1

0.56 (0.26, 1.17)

THP, paclitaxel, trastuzumab and pertuzumab; ddAC, dose-dense doxorubicin and cyclophosphamide; pCR, pathologic complete response; HR, hormone receptor; CI, confidence interval; RCB (0+I), residual cancer burden; EFS, event-free survival

i Data cut-off 12 March 2025; median duration of follow up was 24.2 months with Enhertu followed by THP and 23.6 months with ddAC-THP
ii Based on blinded central review
iii pCR responders were defined as patients who only received randomised study treatment (at least one dose) and had pCR
iv Stratified Miettinen & Nurminen method; p value crossed the 0.03 prespecified boundary
v RCB is based on raw data and is not corrected for non-starters, or any bridging/off study neoadjuvant treatment; therefore, there may be differences between pCR and RCB-0
vi EFS was 4.5% mature at interim analysis

The safety profile of Enhertu followed by THP in DESTINY-Breast11 was consistent with the known profiles of each individual therapy with no new safety concerns identified.

Enhertu followed by THP showed a favourable safety profile compared with ddAC-THP with reduced rates of Grade 3 or higher adverse events (AEs) (37.5% versus 55.8%), serious AEs (10.6% versus 20.2%), treatment interruptions (37.8% versus 54.5%) and left ventricular dysfunction (1.3% versus 6.1%).

Rates of interstitial lung disease (ILD) were low and similar between arms with ILD events occurring in 4.4% of patients in the Enhertu followed by THP arm compared with 5.1% in the ddAC-THP arm. The majority of ILD events were low Grade (Grade 1 and 2). There was one Grade 3/4 event in the Enhertu followed by THP arm and five Grade 3/4 events in the ddAC-THP arm. There was one Grade 5 ILD event in each arm as determined by an independent adjudication committee.

DESTINY-Breast11 results (abstract #291O) will be presented today during Presidential Symposium I, alongside the results from the DESTINY-Breast05 Phase III trial (abstract #LBA1) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress in Berlin, Germany. The DESTINY-Breast11 results will also be published in the Annals of Oncology in parallel with ESMO (Free ESMO Whitepaper).

A supplemental Biologics License Application for Enhertu followed by THP based on the results from DESTINY-Breast11 is currently under review by the US Food and Drug Administration (FDA).

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

Notes

HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

Approximately one in three patients with HER2-positive early breast cancer are considered high-risk, meaning they are more likely to experience disease recurrence and have a poor prognosis.4 For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.5 However, approximately half of patients who receive neoadjuvant treatment do not reach pCR.6-10

The current standard of care in the HER2-positive neoadjuvant setting in many regions of the world consists of combination chemotherapy regimens.11 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiotoxicity, reinforcing the need for new treatment options.11-13

DESTINY-Breast11
DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4 mg/kg) monotherapy or Enhertu followed by THP (paclitaxel, trastuzumab and pertuzumab) versus ddAC-THP in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer.

Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC followed by four cycles of THP.

The Enhertu monotherapy arm was closed early following a recommendation from the Independent Data Monitoring Committee (IDMC). The recommendation was based on multiple factors including a lower pCR rate, low likelihood that Enhertu alone would be superior to ddAC-THP, and timing of surgery. The recommendation was not related to safety.

The primary endpoint of DESTINY-Breast11 is rate of pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety.

DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, 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 (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (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 85 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 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic 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 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (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 (6.4 mg/kg) is approved in more than 70 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-Gastric06 trials. 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 more than 10 countries/regions 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 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme 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.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

(Press release, AstraZeneca, OCT 18, 2025, View Source [SID1234656783])

On October 18, 2025 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported the results of the CHOPIN randomized Phase 2 clinical trial (CHOPIN Trial) presented by Principal Investigator and Lead Author Professor Ellen Kapiteijn, MD, from Leiden University Medical Center’s Department of Medical Oncology at the 2025 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress.

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CHOPIN Trial Design

The investigator-initiated, prospective, randomized Phase 2 CHOPIN Trial was designed to compare the safety, tolerability, and efficacy of Delcath’s CHEMOSAT Hepatic Delivery System (HDS) with melphalan for percutaneous hepatic perfusion (PHP) when used alone versus when combined with the systemic immune checkpoint inhibitors (ICI) ipilimumab and nivolumab. Patients with metastatic uveal melanoma (mUM) were randomized 1:1 to receive PHP alone or in combination with ipilimumab and nivolumab. CHEMOSAT is the device component of the U.S. Food and Drug Administration (FDA) approved combination drug and device product HEPZATO KIT (HEPZATO (melphalan) for Injection/Hepatic Delivery System). HEPZATO KIT is approved for the liver-directed treatment of adult patients with uveal melanoma with unresectable hepatic metastases with less than 50% liver involvement and is administered every six to eight weeks for up to six melphalan/HDS treatments.

Ipilimumab and nivolumab are approved by the FDA and European Union for the treatment of unresectable metastatic melanoma, typically administered intravenously every three weeks for four doses, followed by maintenance nivolumab monotherapy every two to four weeks until disease progression.

The CHOPIN Trial randomized 76 patients 1:1 to receive PHP alone at weeks one and seven (PHP group) or four cycles of ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every three weeks over approximately nine weeks with two PHP treatments at weeks one and seven (combination group). The CHOPIN Trial design did not include additional PHP treatments beyond two treatments or nivolumab maintenance monotherapy. Once the nine-week treatment period was completed patients were monitored until progression. Key eligibility criteria included unresectable hepatic metastases with 50% or less unresectable disease and limited extrahepatic disease. The primary endpoint was one-year progression-free survival; secondary endpoints included safety, best overall response rate, overall survival, and hepatic progression-free survival.

CHOPIN Trial Results

Key Results from the CHOPIN Phase 2 Trial:

Progression-Free Survival (95% CI):
One Year % (95% CI)
Combination group: 54.7% (36.8 – 69.5)
PHP group: 15.8% (5.8 – 30.1)
Median months (95% CI)
Combination group: 12.8 (9.2 – 15.4)
PHP group: 8.3 (6.0 – 9.6)
Hazard Ratio 0.34 (0.19 – 0.60)
P<0.001
Overall Survival – (95% CI):
One Year % (95% CI)
Combination group: 82.8% (65.6 – 91.9)
PHP group: 82.2% (64.5 – 91.6)
Two Year % (95% CI)
Combination group: 49.6% (29.3 – 67.0)
PHP group: 22.1% (7.9 – 40.6)
Median: months (95% CI)
Combination group: 23.1 (20.2 – 38.5)
PHP group: 19.6 (15.2 – 21.8)
Hazard Ratio: 0.39 (0.20 – 0.77)
P = 0.006
Best Overall Response Rate (95% CI):
Combination group: 76.3 (59.4 – 88.0)
PHP group: 39.5 (24.5 – 56.5)
P < 0.001
Grade 3 or higher treatment-related adverse events were more frequent in the combination group (81.6% vs. 40.5%, P<0.001), but most were manageable with standard care. Overall, the combination treatment was well tolerated, with types, rates and frequencies of adverse events consistent with individual use of PHP and checkpoint inhibitors. No new safety signals were identified.

The abstract is available at ESMO (Free ESMO Whitepaper) Congress 2025 – Mini Oral Session LBA59.

"The CHOPIN trial clearly demonstrates that adding ipilimumab and nivolumab to PHP is both effective and tolerable. The efficacy results are impressive, especially when considering the treatment regime included only two PHP treatments and did not include nivolumab maintenance. Since many oncologists start systemic therapy first, this approach provides valuable lead time for patient assessment and scheduling PHP, helping to overcome logistical barriers and support broader adoption and near- to medium-term uptake," said Gerard Michel, Chief Executive Officer of Delcath Systems.

A number of large, randomized clinical trials shows that patients with liver metastases typically have poorer outcomes than those with metastases elsewhere when treated with ICIs across multiple tumor types, including melanoma, non-small-cell lung cancer (NSCLC), urothelial carcinoma, and renal cell carcinoma1, 2. This diminished efficacy of ICIs has been attributed to the well-documented immunosuppressive nature of the liver microenvironment, with underlying mechanisms increasingly understood through preclinical and clinical research3.

"In addition to the potential immediate benefit to patients with metastatic uveal melanoma, the possible synergy of PHP and ICI therapy seen in the successful Phase 2 CHOPIN trial may be transferable to other cancers with liver-dominant disease, and Delcath looks forward to investigating that potential," said Dr. Vojislav Vukovic, Chief Medical Officer of Delcath Systems.

Conference Call Information

Delcath Systems, Inc. will host a conference call and webcast on October 20, 2025, at 8:45 a.m. Eastern Time to discuss the Phase 2 CHOPIN Trial results and provide a brief overview of the financial results and guidance announced in this release. Joining Delcath management on the call with pre-recorded remarks will be Dr. Vincent T. Ma, Assistant Professor and Medical Oncologist at the University of Wisconsin Department of Medicine, a current user of HEPZATO KIT for the treatment of metastatic uveal melanoma patients, an expert in treating cutaneous melanoma, and a co-author on the seminal Nature Medicine paper exploring liver immune tolerance mechanisms in cancer.

To participate in this event, dial in approximately 5 to 10 minutes before the beginning of the call.

Event Date: Monday, October 20
Time: 8:45 AM Eastern Time

Participant Numbers:
Toll Free: 1-877-407-3982
International: 1-201-493-6780
Webcast: View Source;tp_key=6f3953dd75

A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website View Source

(Press release, Delcath Systems, OCT 18, 2025, View Source [SID1234656766])

On October 18, 2025 Astrazeneca reported positive results from the DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) in patients with a high risk of disease recurrence. The trial compared Enhertu with trastuzumab emtansine (T-DM1) as a post-neoadjuvant treatment (after surgery) in patients with HER2-positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant treatment.

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Results showed Enhertu significantly reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1 as a post-neoadjuvant treatment (based on an IDFS hazard ratio [HR] of 0.47, 95% confidence interval [CI] 0.34-0.66, p<0.0001). At three years, 92.4% of patients in the Enhertu arm were alive and free of invasive disease, compared with 83.7% of those in the T-DM1 arm. The IDFS results were consistent across all prespecified subgroups.

Enhertu also significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]), a key secondary endpoint, by 53% (HR 0.47; 95% CI 0.34-0.66; p<0.0001). Further, Enhertu lowered the risk of distant disease recurrence (distant recurrence-free interval [DRFI]) by 51% and the risk of brain metastases (brain metastasis-free interval [BMFI]) by 36% versus T-DM1.

Overall survival (OS) was not mature at the time of this planned interim analysis (2.9% maturity at data cut-off) and will be assessed in future analyses (HR 0.61; 95% CI 0.34-1.10).

Charles Geyer, MD, Chief Scientific Officer of the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP) Foundation, Professor of Medicine at the UPMC Hillman Cancer Center and principal investigator for the trial, said: "For patients with residual disease after neoadjuvant treatment, the post‑neoadjuvant setting represents a critical second opportunity to reduce recurrence risk, and in DESTINY‑Breast05 Enhertu reduced the risk of early recurrence or death by 53 per cent compared to the current standard of T‑DM1. These results, coupled with the safety data from the trial, are likely to transform clinical practice in the post-neoadjuvant setting for patients with high-risk disease, with the potential for Enhertu to set a new standard of care."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Progress in treating HER2-positive early breast cancer has been significant, yet managing patients at a higher-risk of recurrence remains challenging. These landmark data, alongside those from DESTINY-Breast11, underscore the potential of Enhertu to become a foundational treatment in early-stage breast cancer, increasing the likelihood that more patients could be cured in this setting."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The results of DESTINY-Breast05 demonstrate a clear benefit of Enhertu over the current standard of care in patients with high-risk HER2-positive early breast cancer following surgery, improving their chance for sustained long-term outcomes. These results, coupled with the results of DESTINY-Breast11, illustrate the continued promise of Enhertu to move earlier in the breast cancer treatment paradigm where it can have the greatest impact on the lives of patients."

Summary of Results: DESTINY-Breast05i

Efficacy Measure

Enhertu
(5.4 mg/kg; n=818)

T-DM1
(n=817)

IDFSii

3-year IDFS rate, %

92.4

83.7

HR 0.47 (95% CI 0.34-0.66); p<0.0001

DFSiii

3-year DFS rate, %

92.3

83.5

HR 0.47 (95% CI 0.34-0.66); p<0.0001

DRFIiv

3-year event-free rate, %

93.9

86.1

HR 0.49 (95% CI 0.34-0.71)

BMFIv

3-year event-free rate, %

97.6

95.8

HR 0.64 (95% CI 0.35-1.17)

OSvi

Survival at 3 years, %

97.4

95.7

HR 0.61 (95% CI 0.34-1.10)

TDM-1, trastuzumab emtansine; CI, confidence interval; HR, hazard ratio; IDFS, invasive disease-free survival; DFS, disease-free survival; DRFI, distant recurrence-free interval; BMFI, brain-metastasis-free interval; OS, overall survival

i Data cut-off 2 July 2025
ii IDFS is defined as the time from randomisation until the date of first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumour, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause; based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure
iii DFS is defined as the time between randomisation and the date of the first occurrence of an IDFS event per STEEP criteria, including second primary non-breast cancer event, or contralateral or ipsilateral ductal carcinoma in situ (DCIS); based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure
iv DRFI is defined as the time between randomisation and the date of distant breast cancer recurrence; based on investigator assessment
v BMFI is defined as the time between randomisation and the date of documentation of brain metastases or leptomeningeal disease; based on investigator assessment
vi 2.9% maturity

The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified. Grade 3 or higher treatment emergent adverse events (AEs) rates were comparable between Enhertu and T-DM1 (50.6% versus 51.9%). Rates of interstitial lung disease (ILD) were low in both arms with ILD events occurring in 9.6% of the Enhertu arm and 1.6% of the T-DM1 arm. The majority of ILD events were low Grade (Grade 1 or 2). There were no Grade 3 or higher ILD events for T-DMI. There were seven Grade 3 events and no Grade 4 events in the Enhertu arm. There were two Grade 5 events in the Enhertu arm as determined by an independent adjudication committee.

The DESTINY-Breast05 results (abstract #LBA1) will be presented today during Presidential Symposium I alongside the results of the DESTINY-Breast11 Phase III trial (abstract #291O) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress in Berlin, Germany.

DESTINY-Breast05 was conducted in collaboration with the NSABP, the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group.

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

Notes

Post neoadjuvant treatment for HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.4 However, approximately half of patients who receive neoadjuvant treatment do not reach pCR and have poorer long-term outcomes, putting them at increased risk of disease recurrence.5-9

Post-neoadjuvant therapy represents a key opportunity to minimise the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. Despite receiving additional treatment with T-DMI in the post-neoadjuvant setting, approximately 20% of patients still experience invasive disease or death and no reduction in the risk of CNS recurrence.10,11 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.12

New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.

DESTINY-Breast05
DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus T-DM1 in patients with HER2-positive early breast cancer with residual invasive disease in breast and/or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.

The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomisation until first recurrence, distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include OS, distant recurrence-free interval, brain metastases-free interval and safety.

DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, 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 (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridisation (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 85 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 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic 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 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (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 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 70 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-Gastric06 trials. 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 more than 10 countries/regions 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 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme 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.

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.

With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.

To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab).

(Press release, AstraZeneca, OCT 18, 2025, View Source [SID1234656784])