On October 19, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III IMvigor011 study evaluating Tecentriq (atezolizumab) as an adjuvant treatment for people with muscle-invasive bladder cancer (MIBC) who are at risk of recurrence after surgery (cystectomy) and have detectable circulating tumor DNA (ctDNA). In this ctDNA-guided setting, Tecentriq reduced the risk of death (overall survival, OS) by 41% and the risk of disease recurrence or death (disease-free survival, DFS) by 36%, both compared with placebo. This ctDNA-guided approach, using Natera’s SignateraTM ctDNA Molecular Residual Disease (MRD) test, spared people at low risk of recurrence from unnecessary treatment and side effects. The safety profile was consistent with previous studies of Tecentriq.

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These results are being presented as part of the Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. They will also be discussed with health authorities, including the U.S. Food and Drug Administration.

"These clinically meaningful results show that Tecentriq helped people with muscle-invasive bladder cancer live longer and without their disease returning," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "The use of serial ctDNA testing to detect molecular residual disease may also advance bladder cancer treatment by combining a precision diagnostic with cancer immunotherapy."

"Even after surgery, most people with muscle-invasive bladder cancer will face the physical and emotional toll of further treatment," said Thomas Powles, lead principal investigator of IMvigor011, professor of genitourinary oncology; chair of Barts Cancer Centre at St. Bartholomew’s Hospital. "These results indicate that with Signatera ctDNA testing, we may be able to identify those at risk of recurrence who could benefit from adjuvant atezolizumab treatment and spare others from unnecessary therapy, paving the way for a more personalized treatment approach."

At median follow up of 16.1 months, median DFS was 9.9 months in the Tecentriq arm versus 4.8 months in the placebo arm (stratified hazard ratio [HR]=0.64; 95% CI: 0.47-0.87, p=0.0047). Median OS was 32.8 months in the Tecentriq arm versus 21.1 months in the placebo arm (HR=0.59; 95% CI: 0.39-0.90, p=0.0131). People who persistently tested for no detectable ctDNA had low risk of recurrence.

More than 150,000 people worldwide are diagnosed with MIBC each year. It is an aggressive type of cancer, with poor long-term outcomes and high treatment burden. Despite this, personalized treatment approaches lag behind other cancer types. ctDNA-guided treatment could change this, by helping healthcare professionals tailor treatment more precisely to improve clinical benefit and reduce unnecessary intervention.

About the IMvigor011 study
IMvigor011 [NCT04660344] is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with Tecentriq (atezolizumab) compared with placebo in participants with muscle-invasive bladder cancer (MIBC) who are circulating tumor DNA (ctDNA)-positive and are at risk of recurrence following cystectomy. IMvigor011 utilized Natera’s Signatera as the clinical trial assay. This personalized ctDNA test for the detection of MRD is currently under review by the FDA for use as a companion diagnostic. 761 people participated in the surveillance phase of IMvigor011 and those with positive Signatera tests (250 people) joined the treatment phase, where they received either Tecentriq or placebo. The primary endpoint is investigator-assessed disease-free survival (DFS). Secondary endpoints include overall survival (OS) and tolerability, amongst others.

About Tecentriq (atezolizumab)

Tecentriq (atezolizumab) is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

What is Tecentriq?

Tecentriq is a prescription medicine used to treat:

Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as a treatment for your lung cancer:
to help prevent your lung cancer from coming back after your tumor(s) has been removed by surgery and you have received platinum-based chemotherapy, and
you have stage 2 to stage 3A NSCLC (talk to your healthcare provider about what these stages mean), and
your cancer tests positive for "PD-L1".
Tecentriq may be used alone as your first treatment when your lung cancer:
has spread or grown, and
your cancer tests positive for "high PD-L1", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.
Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.

Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as your first treatment when your lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC", and
your tumor does not have an abnormal "EGFR" or "ALK" gene.

Tecentriq may be used alone when your lung cancer:

(Press release, Genentech, OCT 19, 2025, View Source [SID1234656787])
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working.
If your tumor has an abnormal "EGFR" or "ALK" gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

Adults with a type of lung cancer called "extensive stage small cell lung cancer (SCLC)", which is SCLC that has spread or grown

Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as your first treatment
Tecentriq may be used with the medicine lurbinectedin as maintenance treatment when your lung cancer:
has not progressed after first treatment with Tecentriq or atezolizumab and hyaluronidase-tqjs and the chemotherapy medicines carboplatin and etoposide.

Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq may be used with the medicine bevacizumab when your liver cancer:

has spread or cannot be removed by surgery, and
you have not received other medicines by mouth or injection through your vein (IV) to treat your cancer.

Adults with a type of skin cancer called melanoma. Tecentriq may be used with the medicines cobimetinib and vemurafenib when your melanoma:

has spread to other parts of the body or cannot be removed by surgery, and
has a certain type of abnormal "BRAF" gene. Your healthcare provider will perform a test to make sure this Tecentriq combination is right for you.

Adults and children 2 years of age and older with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq may be used when your sarcoma:

has spread to other parts of the body or cannot be removed by surgery.

It is not known if Tecentriq is safe and effective when used:

in children younger than 2 years of age for the treatment of ASPS.
in children for the treatment of NSCLC, SCLC, HCC or melanoma.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during your treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worse signs or symptoms, including:

Lung problems

cough
shortness of breath
chest pain
Intestinal problems

diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems

yellowing of your skin or the whites of your eyes
severe nausea or vomiting
pain on the right side of your stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems
headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
your voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems

decrease in your amount of urine
blood in your urine
swelling of your ankles
loss of appetite
Skin problems

rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes

Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Call or see your healthcare provider right away for any new or worse signs or symptoms, including:

Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Tecentriq. Your healthcare provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Tecentriq. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Tecentriq if you have severe side effects.

Before you receive Tecentriq, tell your healthcare provider about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Tecentriq can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with Tecentriq.
You should use an effective method of birth control during your treatment and for at least 5 months after the last dose of Tecentriq.
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into your breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

Feeling tired or weak
decreased appetite
nausea
cough
shortness of breath

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
decreased appetite

The most common side effects of Tecentriq when used in hepatocellular carcinoma (HCC) with bevacizumab include:

high blood pressure
feeling tired or weak
too much protein in the urine

The most common side effects of Tecentriq when used in melanoma with cobimetinib and vemurafenib include:

skin rash
joint, muscle, or bone pain
feeling tired or weak
liver injury
fever
nausea
itching
swelling of legs or arms
mouth swelling (sometimes with sores)
low thyroid hormone levels
sunburn or sun sensitivity

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of Tecentriq. Ask your healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information and Medication Guide for additional Important Safety Information.

(Press release, Genentech, OCT 19, 2025, View Source [SID1234656787])

On October 19, 2025 Daiichi Sankyo reported initial results from the dose escalation part of the first-in-human phase 1/2 trial of DS-3939 demonstrated promising clinical activity in patients with previously treated advanced solid tumors refractory to standard treatment. These data were presented today during a proffered paper session (917O) at the 2025 European Society for Medical Oncology (#ESMO25).

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DS-3939 is a specifically engineered, potential first-in-class tumor-associated mucin-1 (TA-MUC1) directed DXd antibody drug conjugate (ADC) discovered and being developed by Daiichi Sankyo (TSE: 4568).

TA-MUC1 is a tumor-specific transmembrane glycoprotein that is overexpressed in most human epithelial cancers, making it a promising target for cancer therapy.1,2 Currently, there are no TA-MUC1 directed medicines approved for any type of cancer.

Preliminary safety and efficacy results of DS-3939 were reported from the dose escalation part of the phase 1/2 trial in 64 patients with advanced solid tumors, including 16 with non-small cell lung cancer (NSCLC), 12 with pancreatic ductal adenocarcinoma, nine with urothelial carcinoma, eight with ovarian cancer, seven with biliary tract cancer, seven with colorectal cancer and five with breast cancer.

Patients in the dose escalation phase of the study (n=64) received a median of three prior therapies (range, 1-17) for locally advanced/metastatic disease, including more than one-third receiving prior topoisomerase I inhibitor treatment (n=24; 37.5%). As of the data cut-off on August 1, 2025, 15 patients (23.4%) were still being treated with DS-3939.

The safety and tolerability of DS-3939 was evaluated at increasing dose levels from 1.0 mg/kg to 10.0 mg/kg. The most common treatment-emergent adverse events (TEAEs) of any grade in >20% of patients were nausea (60.9%), vomiting (35.9%), fatigue (28.1%), anemia (26.6%), constipation (26.6%), decreased appetite (23.4%), diarrhea (23.4%) and decreased neutrophil count (23.4%). Grade 3 or higher TEAEs occurred in 46.9% of patients (n=30) and the most common (>2%) included decreased neutrophil count (15.6%), anemia (10.9%), pneumonitis (4.7%) and decreased platelet count (3.1%). There were three dose-limited toxicities observed, including one grade 3 anemia needing transfusion (4.0 mg/kg dose), one grade 3 abdominal pain (6.0 mg/kg dose) and one grade 4 decreased platelet count (8.0 mg/kg dose). All grade adjudicated as treatment-related interstitial lung disease (ILD)/pneumonitis occurred in 10.9% (n=7) of patients. The majority of ILD events were low grade (grade 2 [n=6 or 9.4%]) with one grade 3 (n=1 or 1.6%) event as determined by an independent adjudication committee. Following the data cut-off of August 1, 2025, two ILD events were adjudicated as grade 5 and two additional ILD events are pending adjudication.

Preliminary efficacy results were reported across dose levels from 1.0 mg/kg to 10.0 mg/kg of DS-3939. One confirmed complete response was observed in a patient with ovarian cancer and 10 confirmed partial responses were seen in patients with ovarian cancer (n=5), NSCLC (n=4) and breast cancer (n=1). Thirty-nine cases of stable disease were observed in patients with NSCLC (n=11), urothelial carcinoma (n=8), pancreatic ductal adenocarcinoma (n=6), colorectal cancer (n=5), biliary tract cancer (n=4), breast cancer (n=3) and ovarian cancer (n=2) after a median follow-up of 8.8 months (range, 0.6-22.9).

"These initial results are encouraging for patients with advanced solid tumors where treatment options remain limited once standard therapies are no longer effective," said Manish R. Patel, MD, Director of Drug Development, Florida Cancer Specialists and Sarah Cannon Research Institute. "Enrollment continues into the dose expansion part of the trial to help us better understand the potential role DS-3939 may play in treating numerous types of advanced solid tumors."

"These first-in-human results offer preliminary evidence that targeting the novel tumor antigen TA-MUC1 may be a promising treatment approach for multiple types of cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, these results represent the sixth antibody drug conjugate from the pipeline of Daiichi Sankyo with encouraging early phase data further demonstrating the portability of our DXd antibody drug conjugate technology to new tumor targets."

About the Phase 1/2 Trial
The two-part, multicenter, open-label, first-in-human phase 1/2 trial is assessing the safety and efficacy of DS-3939 in patients with locally advanced, metastatic or unresectable solid tumors not amenable to standard of care treatment for each tumor type.

The first part of the trial (dose escalation) assessed the safety and tolerability of increasing doses of DS-3939 to determine the maximum tolerated dose and/or the recommended doses for expansion (RDEs) in patients with locally advanced, metastatic or unresectable solid tumors.

The second part of the trial (dose expansion) consists of multiple expansion cohorts to assess the safety and efficacy of DS-3939. The trial will evaluate safety endpoints, including dose-limiting toxicities and adverse events, and efficacy endpoints, including objective response rate, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic and biomarker endpoints also will be assessed.

The trial is ongoing and enrolling patients across multiple tumor types at sites globally, including Asia, Europe and North America. For more information, please visit ClinicalTrials.gov.

About TA-MUC1
TA-MUC1, a tumor-specific transmembrane glycoprotein, is a molecular target that is expressed across a broad range of solid tumors, but has limited expression in normal human tissues.1 Based on the overexpression of TA-MUC1 in solid tumors, it is an attractive target for cancer therapy.2 Currently, there are no TA-MUC1 directed therapies approved for any type of cancer.

About DS-3939
DS-3939 is an investigational, potential first-in-class TA-MUC1 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DS-3939 is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo. DS-3939 is comprised of a humanized anti-TA-MUC1 antibody, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Daiichi Sankyo, OCT 19, 2025, View Source [SID1234656803])

On October 19, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress held in Berlin, Germany, results from a Phase 3 OptiTROP-Lung04 trial of the Company’s trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) in EGFR-mutated non-small cell lung cancer (NSCLC) following progression on epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was presented as an oral report by Professor Li Zhang from Sun Yat-sen University Cancer Center (Presentation # LBA5, Presidential Symposium II) and were simultaneously published in the New England Journal of Medicine (Impact Factor = 78.5).

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In the OptiTROP-Lung04 trial, a total of 376 patients were randomized (1:1) to receive sac-TMT monotherapy or chemotherapy.

As at the data cut-off date July 06, 2025, the median follow-up is 18.9 months. the median Progression-Free Survival (PFS) was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group. Sac-TMT significantly improved PFS over chemotherapy with 51% lower risk of disease progression or death (hazard ratio (HR) 0.49; 95% confidence interval (CI), 0.39-0.62; P<0.0001).

At the preplanned interim analysis of overall survival (OS), the OS was not reached (NR) in the sac-TMT group and 17.4 months in the chemotherapy group. sac-TMT significantly improved OS over chemotherapy with 40% lower risk of death (hazard ratio (HR) 0.6; 95% CI: 0.44-0.82; two-sided P=0.001). In the supplemental analysis, when censoring patients at the date of initiation of subsequent ADCs, sac-TMT significantly improved OS over chemotherapy with 44% lower risk of death (HR, 0.56; 95% CI, 0.41 – 0.77).

Sac-TMT significantly improved ORR as compared to chemotherapy (60.6% vs 43.1%)

A consistent PFS and OS benefit of sac-TMT over chemotherapy was observed across all predefined subgroups, including prior EGFR-TKI therapy, presence of liver or brain metastases, and EGFR mutation subtype.

The incidence of any grade treatment-related adverse events (TRAEs) and grade ≥3 TRAEs was similar between the two groups. The most common TRAEs for both sac-TMT and chemotherapy were hematologic toxicities. No TRAEs led to discontinuation or death, and no cases of interstitial lung disease/pneumonitis were reported in the sac-TMT group. Ocular surface toxicity: occurred in 9.6% of patients in the sac-TMT group, all of which were grade 1 – 2.

As a conclusion, sac-TMT demonstrates highly statistically significant and clinically meaningful improvements in PFS and OS compared to platinum-based chemotherapy and showed a manageable safety profile, with no unexpected safety signals identified. Several global phase 3 studies of sac-TMT monotherapy (NCT06305754, NCT06074588) and combination study with osimertinib in China (NCT06670196) in EGFR-mutant NSCLC are ongoing.

Professor Zhang Li, National Lead Principal Investigator from Sun Yat-sen University Cancer Center, commented: "Compared to platinum-based doublet chemotherapy, sac-TMT not only significantly prolonged PFS but also demonstrated a statistically significant and clinically meaningful improvement in OS within this patient population. This achievement marks a major breakthrough in global lung cancer treatment—sac-TMT, as a monotherapy, demonstrated statistically significant and clinically meaningful improvements in both PFS and OS in the Phase III trial for patients with EGFR-TKI-resistant NSCLC. This study provides highly valuable, new evidence-based guidance for lung cancer management worldwide and has the potential to reshape the therapeutic landscape for EGFR-TKI-resistant NSCLC "

About sac-TMT

Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, BC, GC, gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (which includes Mainland China, Hong Kong, Macao and Taiwan).

To date, three indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting), EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy and EGFR mutant-positive locally advanced or metastatic non-squamous NSCLC who progressed after treatment with EGFR-TKI therapy. Sac-TMT is the first TROP2 ADC drug approved for marketing in lung cancer globally. In addition, the new indication applications for sac-TMT for the treatment of adult patients with unresectable locally advanced, metastatic HR+/HER2- BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), and was included in the priority review and approval process.

As of today, the Company has initiated 9 registrational clinical studies in China. MSD has initiated 15 ongoing Phase 3 global clinical studies of sac-TMT as a monotherapy or with pembrolizumab or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD.

(Press release, Kelun, OCT 19, 2025, View Source [SID1234656788])

On October 19, 2025 Merck and Daiichi Sankyo reported results from the phase 2 (dose optimization) part of the REJOICE-Ovarian01 phase 2/3 trial showed that raludotatug deruxtecan (R-DXd) demonstrated clinically meaningful response rates in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer. These data were presented today during a late-breaking proffered paper session (LBA42) at the 2025 European Society for Medical Oncology (#ESMO25) Congress.

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Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 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.

The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens, highlighting the need for new treatment options.3

A confirmed objective response rate (ORR) of 50.5% (95% confidence interval [CI]: 40.6-60.3) was observed in patients (n=107) with platinum-resistant ovarian cancer receiving raludotatug deruxtecan across three doses (4.8 mg/kg, 5.6 mg/kg and 6.4 mg/kg) as assessed by blinded independent central review (BICR). There were 3 complete responses (CRs) and 51 partial responses (PRs) seen, and a disease control rate (DCR) of 77.6% (95% CI: 68.5–85.1) was observed.

In patients receiving the 5.6 mg/kg dose (n=36), a confirmed ORR of 50.0% (95% CI: 32.9–67.1) was observed as assessed by BICR with two CRs (5.6%), 16 PRs (44.4%) and a DCR of 80.6% (95% CI: 64.0–91.8). Clinically meaningful tumor responses were seen irrespective of dose and across a range of CDH6 expression levels.

The safety profile of raludotatug deruxtecan observed in REJOICE-Ovarian01 is consistent with safety findings from the phase 1 trial with no new safety signals identified. Nausea, anemia, asthenia and neutropenia were the most common treatment-emergent adverse events (TEAEs) across all doses. Treatment discontinuations due to treatment-related TEAEs occurred in 8.3% (n=3), 0.0% (n=0) and 8.6% (n=3) in the 4.8 mg/kg, 5.6mg/kg and 6.4 mg/kg groups, respectively. Grade 3 or higher treatment-related TEAEs occurred in 27.8% (n=10), 30.6% (n=11), and 48.6% (n=17) of patients in the 4.8 mg/kg (n=36), 5.6 mg/kg (n=36), and 6.4 mg/kg (n=35) groups, respectively.

The most common TEAEs (≥10% of total population) in the 5.6 mg/kg cohort included nausea (69.4%), anemia (58.3%), asthenia (50.0%), neutropenia (44.4%), vomiting (33.3%), constipation (27.8%), decreased appetite (25.0%), thrombocytopenia (19.4%), AST increase (16.7%), diarrhea (16.7%) and leukopenia (13.9%). Four (3.7%) interstitial lung disease (ILD)/pneumonitis events were confirmed as treatment-related across all doses as determined by an independent adjudication committee. The majority of ILD events (one with 5.6 mg/kg, two with 6.4 mg/kg) were low grade (grade 1 or 2). One grade ≥3 (4.8 mg/kg) ILD event was reported. Based on these efficacy and safety results, the 5.6 mg/kg dose has been selected for the phase 3 part of the trial.

"When ovarian cancer becomes resistant to platinum-based chemotherapy, treatment options for patients become limited," said Isabelle Ray-Coquard, MD, PhD, President, ENGOT (European Network of Gynecological Oncology Trial) Group, Trial Leader, National Group of Investigators on the Studies of Ovarian and Breast Cancer (GINECO), and Medical Oncologist, Centre Léon Bérard, Lyon, France. "These promising results from the first part of REJOICE-Ovarian01 suggest that raludotatug deruxtecan may have an important role in treating patients with platinum-resistant ovarian cancer and support further evaluation in the phase 3 portion of this trial."

"In this dose optimization analysis, rapid responses with impressive disease control have been observed with raludotatug deruxtecan across a range of CDH6 expression levels," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "These results, which contributed to the recent Breakthrough Therapy Designation in the U.S., reinforce the potential for raludotatug deruxtecan to become a new treatment option for certain types of patients with platinum-resistant ovarian cancer."

"While we have seen targeted treatment advancements and improved outcomes in ovarian cancer in recent years, there is still a high unmet need for additional options for patients," said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. "CDH6 is highly expressed in ovarian cancer, which underscores the potential of raludotatug deruxtecan to make an impact."

In September 2025, raludotatug deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab.

Median follow-up for the 4.8-mg/kg, 5.6-mg/kg and 6.4-mg/kg cohorts was 5.6 months (95% CI: 4.7–6.3), 5.6 months (95% CI: 4.6–5.8), and 5.2 months (95% CI: 4.9–5.8), respectively. A majority of patients (51.4%) in REJOICE-Ovarian01 received three prior lines of treatment, including bevacizumab (n=89; 83.2%), PARP inhibitor (n=75; 70.1%) and mirvetuximab soravtansine (n=3; 2.8%). As of the data cut-off of February 26, 2025, 66 patients (61.7%) remain on treatment with raludotatug deruxtecan.

Summary of REJOICE-Ovarian01 Results

Efficacy Measure

Raludotatug
Deruxtecan
Across 4.8, 5.6 and 6.4
mg/kg (n=107)

Raludotatug
Deruxtecan
6.4 mg/kg
(n=35)

Raludotatug
Deruxtecan
5.6 mg/kg
(n=36)

Raludotatug
Deruxtecan
4.8 mg/kg
(n=36)

Confirmed ORR, % (95% CI)1

50.5%

(40.6–60.3)

57.1%

(39.4–73.7)

50.0%

(32.9–67.1)

44.4%

(27.9–61.9)

CR, n (%)

3 (2.8%)

0

2 (5.6%)

1 (2.8%)

PR, n (%)

51 (47.7%)

20 (57.1%)

16 (44.4%)

15 (41.7%)

SD, n (%)

42 (39.3%)

10 (28.6%)

15 (41.7%)

17 (47.2%)

PD, n (%)

8 (7.5%)

4 (11.4%)

2 (5.6%)

2 (5.6%)

NE, n (%)

3 (2.8%)

1 (2.9%)2

1 (2.8%)3

1 (2.8%)2

DCR, %

(95% CI)

77.6%

(68.5–85.1)

77.1%

(59.9–89.6)

80.6%

(64.0–91.8)

75.0%

(57.8–87.9)

TTR, weeks, median (range)

7.1 weeks

(5.1–19.1)

7.2 weeks

(5.3–19.1)

6.6 weeks

(5.1–18.3)

7.1 weeks

(5.4–18.7)

Data cutoff: February 26, 2025.

1As accessed by BICR per RECIST 1.1. 2Patient had no baseline tumor assessment by BICR. 3Patient had no adequate post-baseline tumor assessment by BICR.

BICR, blinded independent central review; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease; TTR, time to response.

About REJOICE-Ovarian01
REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior lines of systemic therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.

The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by BICR. Key secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator.

The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.

REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer
More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.4 The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2

The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.5 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.3 For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7

About CDH6
CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% to 94% of patients with ovarian cancer have tumors that express CDH6.9,10,11 In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.9, 10,11 There is currently no CDH6 directed medicine approved for treatment of any cancer.

About Raludotatug Deruxtecan
Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

(Press release, Merck & Co, OCT 19, 2025, View Source [SID1234656804])

On October 19, 2025 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 hematologic malignancies and solid tumors, reported that the latest results from the ongoing Phase I/II CLINCH study of ATG-022 (CLDN18.2 antibody-drug conjugate [ADC]), were presented in a Poster Presentation at the European Society for Medical Oncology Congress 2025 (ESMO 2025) in Berlin, Germany.

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Details of the Poster Presentation:
ATG-022 (CLDN18.2 antibody-drug conjugate)
Title: Phase I/II study of Claudin 18.2 ADC ATG-022 in patients with advanced gastric/ gastroesophageal junction cancer (CLINCH)
Abstract Number: 2907
Presentation Number: 2113P

ATG-022 and CLINCH Study Overview

ATG-022 is a CLDN18.2-targeted ADC with sub-nM affinity and fast internalization. Using a VC-MMAE linker-payload (DAR 4), ATG-022 has demonstrated potent activity across tumors with high, low, and ultra-low CLDN18.2 expression.
The ongoing Phase I/II CLINCH study consists of dose escalation and dose expansion phases. In dose escalation, patients with advanced solid tumors regardless of CLDN18.2 expression receive ATG-022 once every three weeks (0.3-3.0 mg/kg Q3W) to evaluate the safety, tolerability, and pharmacokinetics; CLDN18.2-positive (≥ IHC 1+, 1%) patients are treated at 1.8 mg/kg or 2.4 mg/kg in dose expansion to evaluate the efficacy and safety.
ATG-022 has been granted two Orphan Drug designations (ODDs) by the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer and pancreatic cancer, and in August 2025 obtained Breakthrough Therapy Designation from China’s National Medical Products Administration (NMPA) for treating CLDN18.2-positive, HER-2 negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) who have received at least two prior lines of therapy.
Key Results from the CLINCH Study

Efficacy Data
Among GC/GEJC patients with moderate/high CLDN18.2 expression (IHC 2+ > 20%), the 2.4 mg/kg dose cohort observed 1 complete response (CR), 11 partial responses (PRs) and 15 stable diseases (SDs), resulting in an objective response rate (ORR) of 40% (12/30) and a disease control rate (DCR) of 90% (27/30). The median progression-free survival (mPFS) was 6.97 months and the 12-month overall survival (OS) rate was 66.2%. In the 1.8 mg/kg dose cohort, there were 1 CR, 9 PRs, and 11 SDs, resulting in an ORR of 40% (10/25) and a DCR of 84% (21/25).
Among GC/GEJC patients with low/ultra low CLDN18.2 expression (IHC 2+ ≤ 20%), patients treated at the efficacious dose of 1.8-2.4 mg/kg achieved 1 CR and 5 PRs, resulting in an ORR of 33.3% (6/18) and a DCR of 50% (9/18). The patient with CR has demonstrated durable response and has been on the study for over 22 months.
To date, the study has observed three CRs, one from each of the three forementioned cohorts (two dose cohorts among CLDN18.2 mid/high expressors and the cohort of low/ultra low CLDN18.2 expressors). This broad-spectrum antitumor activity indicates ATG-022’s potential as a new treatment option for a broader population of patients).
Safety Data
At 2.4 mg/kg in the dose expansion, 45.8% of patients had ≥1 treatment-emergent adverse events (TEAEs), 60.4% of patients had grade ≥3 TEAEs. The most common grade ≥3 treatment-related adverse events (TRAEs, ≥5% of patients) were neutrophil count decrease (16.7%), decreased appetite (14.6%) and anaemia (8.3%).
In the dose-expansion phase, the 1.8 mg/kg cohort demonstrated excellent safety and tolerability, with only 13.6% of patients reporting serious TEAEs and 18.2% reporting Grade ≥3 TEAEs. The favorable safety profile of this dose level support its potential use in first-line combination regimens with chemotherapy and immune checkpoint inhibitors.
No ophthalmological toxicities or interstitial lung disease have been observed.
Conclusions and Outlook

ATG-022 demonstrated a manageable safety profile and encouraging antitumor effects in GC/GEJC adenocarcinoma patients with a broad range of CLDN18.2 expressions, thus supporting further clinical investigation in patients with variable CLDN18.2 expressions. In addition to GC/GEJC, preliminary efficacy has been observed in other non-GI tumor types which will be reported at upcoming conferences.
The 2.4 mg/kg cohort showed a favorable safety profile, while the 1.8 mg/kg cohort demonstrated even better safety and tolerability. These findings provide strong support for advancing ATG-022 in combination with immune checkpoint inhibitors and chemotherapy in first-line treatment settings, paving the way to significantly expand its clinical reach and commercial potential.
The Phase II dose expansion study of ATG-022 is going smoothly in China and Australia. In parallel, Antengene is actively preparing for combination therapy studies involving ATG-022 to further advance its clinical development.

(Press release, Antengene, OCT 19, 2025, View Source [SID1234656789])