Latest news with #PDL1
Yahoo
04-08-2025
- Business
- Yahoo
Alphamab Oncology Announces IND Application for Innovative PD-L1/αvβ6 Bispecific ADC JSKN022 was Officially Accepted by CDE
SUZHOU, China, Aug. 4, 2025 /PRNewswire/ -- Alphamab Oncology (stock code: announced that the Investigational New Drug (IND) application for JSKN022, an independently developed innovative bispecific antibody-drug conjugate (ADC) targeting PD-L1 and integrin αvβ6, has been officially accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The Company plans to initiate a first-in-human (FIH) clinical study of JSKN022 for the treatment of advanced malignant solid tumors. JSKN022 is an innovative bispecific ADC developed in-house with Alphamab's proprietary glycan-specific conjugation platform. The molecule simultaneously targets and binds to both PD-L1 and integrin αvβ6 on the surface of tumor cells. After binding to either target, JSKN022 enters the lysosome through target-mediated endocytosis. The cleavable linker is specifically hydrolyzed by proteolytic enzymes such as cathepsin B, releasing cytotoxic topoisomerase I inhibitor (T01), which then induces apoptosis of PD-L1 and/or integrin αvβ6 positive tumor cells. In addition, the inhibitor can penetrate the cell membrane and enter the antigen-negative tumor cells to exert bystander effects. These combined effects can effectively inhibit the growth of tumor cells. At present, no ADC targeting integrin αvβ6 or PD-L1 has been approved for marketing worldwide, with all related investigational candidates remaining in clinical development stages. Preclinical data demonstrate that JSKN022 exhibits potent antitumor activity in both in vitro and in vivo models against tumor cells expressing integrin αvβ6 and/or PD-L1. JSKN022 will potentially bring in novelty in the therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors, including non-small cell lung cancer, head and neck squamous cell carcinoma, and colorectal cancer. This Phase I clinical study will evaluate the safety, tolerability, pharmacokinetics (PK)/pharmacodynamics (PD), and antitumor activity of JSKN022 in patients with advanced malignant solid tumors who have failed standard therapies, and determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D). About JSKN022JSKN022 is a first-in-class ADC targeting both PD-L1 and integrin αvβ6. Based on independently developed Envafolimab, Alphamab integrates immuno-oncology (IO) mechanisms with ADC approaches. This novel drug molecule utilizes glycan-specific conjugation technology to enhance both stability and homogeneity. The topoisomerase I inhibitor T01 is site-specifically conjugated to antibodies via a cleavable linker, enhancing therapeutic efficacy. JSKN022 is expected to provide a novel therapeutic option for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors. The IND application for the first-in-human clinical study of JSKN022 for the treatment of advanced malignant solid tumors has been accepted by CDE. About Alphamab OncologyAlphamab Oncology is an innovative biopharmaceutical company focusing on oncology therapeutics. On December 12, 2019, the Company was successfully listed on the Main Board of the Hong Kong Stock Exchange, trading under the stock code 9966. By leveraging its proprietary core technology platforms including single-domain antibodies, bispecific antibodies, glycan-specific conjugation, linker-payload, dual-payload antibody conjugation, and subcutaneous high concentration formulation for biologics, the Company has established a product portfolio with differentiated innovation and global competitiveness, covering cutting-edge areas such as antibody-drug conjugates (ADCs), bispecific antibodies, and single-domain antibodies. The Company has one product approved for marketing (Envafolimab, the world's first subcutaneously injectable PD-(L)1 inhibitor), which has made a significant breakthrough in the convenience and accessibility of cancer treatment. Additionally, the Company has multiple bispecific antibodies and bispecific ADCs in clinical stage, while rapidly advancing the preclinical pipeline prioritizing bispecific ADCs and dual-payload ADCs. Multiple strategic collaborations based on innovative products or technology platforms have been established with partners such as CSPC, ArriVent, and Glenmark. Our overarching mission is to make cancer manageable and curable by addressing unmet clinical needs in oncology. Alphamab Oncology is continuously dedicated to the development of effective, safe, and globally competitive anti-tumor drugs, delivering China-innovated cancer therapies to benefit patients worldwide. View original content: SOURCE Alphamab Oncology Sign in to access your portfolio
Medscape
16-07-2025
- Health
- Medscape
Fact or Fiction: Bladder Cancer
Recent advances in immunotherapy, genomic profiling, and bladder-sparing techniques have begun to reshape diagnostic algorithms and treatment strategies across disease stages, from non-muscle-invasive to metastatic bladder cancer. Immunotherapies targeting PD-1 and PD-L1 have shown durable responses in certain subsets of patients, while next-generation sequencing helps guide decisions by identifying actionable mutations and molecular subtypes. Additionally, minimally invasive surgical techniques, improvements in intravesical therapies, and novel surveillance tools such as urinary biomarkers contribute to a more personalized, risk-adapted approach. As the field moves toward more integrated, multidisciplinary care, clinicians and care teams must stay abreast of these innovations to ensure optimal outcomes, improved quality of life, and equitable access to cutting-edge therapies. Checkpoint inhibitors such as atezolizumab, nivolumab, and pembrolizumab have been approved for patients with advanced or metastatic urothelial carcinoma, especially those ineligible for cisplatin-based chemotherapy or with disease progression after platinum therapy. These agents work by targeting PD-1 or PD-L1 pathways to enhance the immune system's ability to fight cancer. In recent years, nivolumab was approved for use in combination with cisplatin and gemcitabine as first-line treatment for unresectable or metastatic urothelial carcinoma, marking a major shift toward integrating immunotherapy earlier in treatment algorithms. Learn more about immunotherapy for bladder cancer. Cigarette smoking is the leading risk factor for bladder cancer, responsible for approximately 50% of all cases. Smokers are twice as likely to develop bladder cancer than nonsmokers. Smoking cessation significantly reduces risk over time, though former smokers remain at elevated risk compared to never-smokers. Occupational exposures, such as to benzidine and beta-naphthylamine, are also important, especially for long-term workers in underregulated environments. However, these exposures account for a smaller percentage of overall cases. Environmental exposures are increasingly being realized as a cause for bladder cancer. Pesticides and contaminated drinking water are concerns. Learn more about bladder cancer etiology. The majority of NMIBC cases are managed conservatively, starting with transurethral resection of bladder tumor (TURBT). At recurrence, however, intravesical therapy with instilled chemotherapy drugs, Bacillus Calmette-Guérin (BCG), and immediate radical cystectomy are options that should be discussed. Radical cystectomy is generally reserved for patients who are unresponsive to or who have high-grade T1 lesions with associated carcinoma in situ, lymphovascular invasion, or variant histology. Bladder preservation is a cornerstone of treatment for low- and intermediate-risk patients with NMIBC, aiming to maintain quality of life while achieving cancer control. Surveillance through periodic cystoscopy and urinary cytology is essential to detect recurrences, which are common. Learn more about treatment for NMIBC. Although several urinary biomarkers (eg, NMP22, UroVysion FISH, Cxbladder, bladder tumor antigen tests) are available, they have not replaced cystoscopy, which remains the cornerstone of surveillance. Cystoscopy provides direct visualization and allows for resection of visible tumors, whereas biomarkers have variable sensitivity and specificity with the potential for false positives. Urinary biomarkers are being incorporated as adjuncts to traditional surveillance, however, as they offer minimal discomfort and invasiveness for patients. Ongoing research is exploring novel biomarker panels and genomic assays to better personalize surveillance regimens and reduce the burden of routine cystoscopy without compromising oncologic safety. Learn more about long-term monitoring for bladder cancer. Neoadjuvant cisplatin-based chemotherapy, typically gemcitabine plus cisplatin (GC) or methotrexate-vinblastine-doxorubicin-cisplatin (MVAC), has been shown to improve overall survival, with some studies finding a 10% benefit in 5-year survival. As a result, neoadjuvant chemotherapy is considered a standard of care for eligible patients with muscle-invasive bladder cancer. For cisplatin-ineligible patients, ongoing trials are evaluating alternative treatment options in the neoadjuvant setting. Molecular subtyping, while there is not yet currently sufficient evidence to be the standard of care, may help to inform treatment decision-making and offer the potential for more targeted therapies. Learn more about neoadjuvant therapy for bladder cancer.
Medscape
24-06-2025
- Health
- Medscape
PD-L1 Did Not Predict Immunotherapy Benefit in CC
Findings of the BEATcc trial suggest PD-L1 status is not a reliable biomarker for guiding immunotherapy selection in patients with recurrent or metastatic cervical cancer, potentially simplifying treatment decisions for clinicians managing this patient population. A post-hoc analysis of the phase 3 trial demonstrated that the addition of atezolizumab to chemotherapy plus bevacizumab provided clinical benefit regardless of PD-L1 combined positive score (CPS) status. This was among the results of the trial that Kristina Lindemann, MD, head of the Gynecological Oncology Center at Oslo University Hospital, Norway, presented at the European Society for Medical Oncology Gynecological Cancers Congress 2025. Current Treatment Landscape The treatment landscape for recurrent or metastatic cervical cancer has evolved significantly in recent years, according to Lindemann. Since the publication of GOG-240, platinum-based chemotherapy with or without bevacizumab has served as the standard of care for chemotherapy-naive patients. She noted, during her presentation, that the Keynote 826 study further established pembrolizumab plus chemotherapy and bevacizumab as a treatment option, but only for biomarker-positive patients with a CPS of at least 1. The question that remains now is 'can we further improve the efficacy' of chemotherapy by adding immunotherapy in the biomarker-negative population, that is in those with a CPS of less than 1 or an unknown PD-L1 status? BEATcc Trial Design and First Results The BEATcc trial was an open-label, multicenter randomized phase 3 study in an all-comer population of 410 patients with recurrent or metastatic cervical cancer who had received no prior systemic anticancer therapy. Patients were randomized 1:1 to receive either atezolizumab plus bevacizumab and platinum-based chemotherapy or the control arm of bevacizumab and platinum-based chemotherapy alone. The trial met its dual primary endpoints of progression-free survival (PFS) and interim overall survival (OS). Lindemann reported that the addition of atezolizumab to the backbone of chemotherapy and bevacizumab significantly increased both PFS and interim OS, with an increase in median PFS from 10.4 months to 13.7 months (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78). Median OS was 32.1 and 22.8 months, respectively (HR, 0.68; 95% CI, 0.52-0.88). Biomarker Analysis The post hoc analysis presented by Lindemann examined treatment efficacy according to PD-L1 status in 313 patients (76% of the randomized population) who had available CPS scores. The analysis showed that the addition of atezolizumab to chemotherapy and bevacizumab provided benefit across all CPS subgroups. In the CPS-negative group (CPS < 1), PFS improved from 10.2 months in the control group to 13.6 months with atezolizumab (HR, 0.48; 95% CI, 0.28-0.82). Similarly, in the CPS-positive group (CPS ≥ 1), the median PFS increased from 10.5 months to 16.6 months (HR, 0.54; 95% CI, 0.39-0.74). Interaction tests showed no predictive effect of CPS for PFS ( P = .73), PFS2 ( P = .53), or OS ( P = .12). Commenting on these data, Lindemann emphasized that 'atezolizumab demonstrates efficacy in terms of providing a significant beneficial effect on PFS as well as interim OS, both in the intention-to-treat population, but also in the biomarker-evaluable population, and this efficacy was seen across all CPS cut-offs.' Stéphanie Lheureux, of Princess Margaret Cancer Centre, Toronto, Ontario, who served as the external discussant, provided context regarding the interpretation of these biomarker analyses. She highlighted critical differences between the BEATcc and Keynote 826 trials in their approach to biomarker assessment. 'It's important to note that for both trials, the primary endpoint was a dual primary endpoint with both OS and PFS, which was powered for the trial design. They both used the same specific CPS core biomarker, but the way they analyzed the biomarker was very different in the two trials,' Lheureux noted. She explained that, in Keynote 826, CPS score was prospectively assessed as a stratification factor and was well-balanced between groups, with CPS < 1 representing about 10% of the population. In contrast, the BEATcc biomarker analysis was conducted as a post hoc analysis, with 24% of patients lacking CPS scores and some imbalance between treatment groups. 'We need to be very careful when we look at subgroup analysis. The clinical trial design matters very much when we analyze the results,' Lheureux cautioned. 'If the subgroup analysis is not powered, it could just be hypothesis generating, and we need to be very careful of how we interpret this.' Clinical Implications and Future Perspectives The findings of BEATcc have already influenced clinical practice guidelines. 'The BEAT regimen is now listed as a preferred first-line regimen in these patients' in the updated National Comprehensive Cancer Network guidelines, reflecting the potential for broader application of atezolizumab regardless of biomarker status, Lindemann explained. Looking ahead, Lheureux emphasized that more sophisticated approaches to personalized treatment selection using biomarkers are needed. "We need to make sure biomarkers are context specific and appropriately validated with the right rigorous trials, and we need to assess the potential evolution of this biomarker with the tumor evolution and heterogeneity,' she said. Lindemann said the final OS analysis from the BEATcc trial is expected in 2026, which may provide additional insights into the long-term benefits of the atezolizumab combination across different biomarker subgroups. 'In the BEATcc trial, PD-L1 status does not seem to be a robust biomarker guiding patient selection for immunotherapy in this setting.' The findings suggest that atezolizumab, in combination with bevacizumab and chemotherapy, 'represents an effective first-line treatment option for patients with recurrent [or] metastatic cervical cancer and should actually be offered irrespective of CPS,' she concluded. Lindemann reports financial relationships with GSK, MSD, AstraZeneca, Karyopharm, Eisai, and Genmab. Lheureux reports financial relationships with AstraZeneca, Repare Therapeutics, GSK, Schrodinger, Merck, Roche, Seagen, AbbVie, Zai Lab, Gilead, and Eisai.
Medscape
20-06-2025
- Health
- Medscape
ASCO 2025: New Standards Reshape Care in mBC
Heather McArthur, MD, describes how the 2025 ASCO Annual Meeting brought exciting advances in the metastatic breast cancer space. In PD-L1-positive triple-negative breast cancer, sacituzumab govitecan combined with pembrolizumab significantly improved progression-free survival over standard chemotherapy plus pembrolizumab, quickly becoming a new standard of care. Similarly, in HER2-positive disease, trastuzumab deruxtecan combined with pertuzumab outperformed traditional THP therapy, offering a new frontline option. Overall, these findings signify a major shift in how to treat metastatic breast cancer.
Medscape
11-06-2025
- Health
- Medscape
Can a TKI Boost Anti-PD-L1 Activity in NSCLC?
Can adding a TKI that targets programmed death ligand 1 (PD-L1) to a monoclonal antibody that also targets PD-L1 improve outcomes over the monoclonal antibody alone in locally advanced, unresectable non-small cell lung cancer (NSCLC)? Researchers in China have come in with a qualified yes. The authors of the new study found that a combination of anlotinib, an oral small-molecule TKI, and benmelstobart (TQB2450), a humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody that targets PD-L1, improved progression-free survival (PFS) compared with benmelstobart alone after concurrent/sequential chemoradiotherapy (60 Gray ± 10%). A downside of taking the TKI was a significant increase in side effects, Ming Chen, MD, PhD, lead investigator of the R-ALPS trial, reported at American Society of Clinical Oncology (ASCO) 2025. Study Results 'Our key finding demonstrated significant improvement in median PFS with the combination of benmelstobart plus anlotinib, with a median PFS of 15.1 months compared to 9.7 months with benmelstobart alone and 4.2 months with placebo,' said Chen, while presenting the abstract at the meeting. PFS was the primary endpoint of the study. Ming Chen, MD, PhD 'This translated into a reduced risk of disease progression with a hazard ratio of 0.49 for the combination arm and 0.53 for benmelstobart alone,' vs placebo, said Chen, who is director of Radiation Oncology at the Sun Yat-sen University Cancer Center in Guangzhou, China. The P values for both were less than .0001. Chen reported results of an interim analysis of the phase 3 R-ALPS study, which randomized 553 patients to one of three treatment groups after all received concurrent/sequential chemoradiotherapy: Benmelstobart alone, benmelstobart plus anlotinib, or placebo. Twelve-month PFS rates were 54.9% in the combination group, 45.7% in the benmelstobart alone group, and 26.4% in the placebo group. The data analysis of overall survival rates has not been completed, Chen said. Among secondary endpoints, overall response rates were 25.6% ( P = .01), 23.3 ( P = .0318), and 12.9% for the combination, benmelstobart alone, and placebo groups, respectively. The disease control rates were 84.5% ( P = .0067) and 86.1% ( P = .0023) for the combination and benmelstobart alone groups, respectively, and was 70.5% for the placebo group. Safety Profile 'Manageable' or 'Significant'? The combination group had consistently higher rates of adverse events than the other two groups. Chen said the safety profile of adding anlotinib to benmelstobart was 'manageable,' while Shankar Siva, PhD, MBBS, a discussant at the oral abstracts session, characterized the toxicity profile of the study as 'significant.' Shankar Siva, PhD, MBBS Overall, the rates of grade 3-5 treatment-related adverse events (TRAEs) were 50% in the combination group, 32% in the benmelstobart alone group, and 21% in the placebo group. The rates of serious TRAEs were 38.3%, 33% and 26.5%, respectively. Hematologic toxicities were not significantly different across the three groups, Chen said, but the following four biochemical measures were significantly elevated in the combination group: Antistreptokinase, creatine phosphokinase, thyroid-stimulating hormone, and amylase. Among the grade 3-5 non-hematologic TRAEs, rates of infectious pneumonia, hypertension, and hemoptysis were significantly higher in the combination group: 8.1%, 8.6%, and 2.4%, respectively, vs 4.7%, 0.9%, and 0.5% in the benmelstobart alone group and 5.3%, 1.8%, and 0.8% in the placebo group. Chen added that the rates of radiation pneumonitis and immune pneumonitis 'were very mild in all three arms,' with rates below 3%. Elaborating on his different take on the combination treatment's safety profile from Chen's, Siva said the incidence of high-grade adverse events in this study was notable. 'More targeted or bispecific TKIs' might be worth exploring in a combination treatment after chemoradiotherapy for NSCLC to improve the safety profile, he said, during the session. Knowing biomarkers of benefit and potential toxicity would also be important for using multitarget TKIs in combination therapies after chemoradiotherapy for NSCLS, noted Siva, who is a radiation oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia. One of the limitations of the study was that all patients were Chinese, Chen said. Anlotinib was approved for advanced NSCLC in China in 2019. Chia Tai TianQing Pharmaceutical Group funded the study. Chen reported having no relevant financial relationships. Siva reported having financial relationships with AstraZeneca, Bayer, Bristol Myers Squibb, Merck Sharp & Dohme, and Varian Medical Systems.
