On September 22, 2025 Servier, an independent international pharmaceutical group governed by a foundation, reported that the European Commission (EC) has approved VORANIGO (vorasidenib) for the treatment of predominantly non-enhancing Grade 2 astrocytoma or oligodendroglioma with an isocitrate dehydrogenase-1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation in adult and adolescent patients aged 12 years and older and weighing at least 40 kg who only had surgical intervention and who are not in immediate need of radiotherapy or chemotherapy (Press release, Servier, SEP 22, 2025, View Source [SID1234656157]). The decision to approve VORANIGO as the first targeted therapy to treat Grade 2 IDH-mutant glioma follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in July 2025.

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Gliomas are types of brain cancer that can hinder normal brain function and cause a variety of symptoms. Diffuse gliomas with IDH mutations represent the most common malignant primary brain tumors diagnosed in adults younger than 50 years of age. Historically, treatment options have been limited, and tumors continue to grow and infiltrate normal brain tissue without treatment.1,2,3

"Today’s EU approval of VORANIGO is a landmark moment for people in the EU living with IDH-mutated glioma who have been waiting more than two decades for new treatment options. VORANIGO is the first EMA-approved therapy specifically designed to target mutant IDH enzymes in Grade 2 glioma and represents a long-awaited shift in the treatment paradigm. As a leader in precision medicine, we’re grateful to the researchers, patients and advocates who have helped expand our understanding of IDH inhibition and bring this breakthrough to the EU," said Islam Hassan, Global Head of Development-Neuro-Oncology & Senior Director, LS/LCM at Servier.

Decisions by the EC are applicable in the 27 member states of the EU, as well as Norway, Liechtenstein, and Iceland.

The approval of VORANIGO is supported by results from the pivotal Phase 3 INDIGO clinical trial published in The New England Journal of Medicine and presented during the Plenary Session at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which showed that VORANIGO significantly extended progression-free survival (PFS) and time to next intervention (TTNI) when compared to placebo. The INDIGO study showed that VORANIGO was well tolerated, and its safety profile was consistent with results from the Phase 1 studies. The most common (≥15%) adverse reactions were fatigue, COVID-19, musculoskeletal pain, diarrhea and seizure.4

VORANIGO has also been granted marketing authorization in the United States, Canada, Australia, Israel, the United Arab Emirates, Saudi Arabia, Switzerland, Brazil, the United Kingdom, and Japan. Servier has submitted marketing authorization applications in several other regions as well and reviews by the respective health authorities are ongoing.

On September 22, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that a new drug application (NDA) for the Company’s small molecule rearranged during transfection (RET) kinase inhibitor A400 (also known as EP0031) was accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China for the treatment of adult patients with RET-fusion positive locally advanced, or metastatic non-small cell lung cancer (NSCLC) (Press release, Kelun, SEP 22, 2025, View Source [SID1234656156]). This acceptance for review is based on the positive results from the two pivotal Phase 2 cohorts of the KL400-I/II-01 study for both 1L and 2L+ advanced RET-fusion positive NSCLC.

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Cohort 1 and 2, the Phase 2 stage of the KL400-I/II-01 study, evaluate the efficacy and safety of A400/EP0031 90mg orally once daily (QD) for the treatment of patients with pre-treated and treatment-naïve RET-fusion positive locally advanced, or metastatic NSCLC, respectively. Primary efficacy endpoints of the two pivotal cohorts were reached, where A400/EP0031 demonstrated favorable efficacy in pretreated and treatment-naïve NSCLC including patients with prior immunotherapy or brain metastases. A400/EP0031 also demonstrated an encouraging, manageable tolerability and safety profile.

Dr. Michael Ge, CEO of Kelun-Biotech said, "We are pleased to report positive results from the clinical study of A400/EP0031 in treating RET-fusion positive NSCLC, which gives us confidence in its future clinical potential. As a tumor agnostic precision therapy, A400/EP0031 represents our significant strategic positioning in the solid tumor field. We look forward to working closely with regulatory authorities to expedite the review process for A400/EP0031, bringing this innovative therapy to patients with RET-fusion positive NSCLC as soon as possible."

About RET-fusion positive NSCLC

RET gene fusions represent one of the rare yet significant driver mutation types in NSCLC. In Chinese NSCLC patients, the incidence of RET gene fusions ranges from 1.4% to 2.5%[1]. Patients with RET fusions derive limited benefit from conventional treatments. In recent years, the emergence of novel highly selective inhibitors has led to breakthroughs in the clinical management of advanced RET-fusion positive NSCLC patients. However, their therapeutic benefits are limited, in part, by acquired RET drug-resistant mutations and safety issues such as hypertension and hematological toxicity, underscoring the need for novel selective RET inhibitors with improved safety and better efficacy against drug-resistant mutations.

About A400/EP0031

A400/EP0031 is a novel next-generation selective RET inhibitor for NSCLC, medullary thyroid cancer (MTC) and other solid tumors with a high prevalence of RET alterations. The Company is currently conducting a phase 1b/2 clinical study for RET+ MTC and solid tumor in China. The results from the Phase 1 study of A400/EP0031 in patients with advanced RET-mutant MTC were presented at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting.

In March 2021, the Company granted Ellipses Pharma Limited, a U.K.-based international oncology drug development company, an exclusive license to develop, manufacture and commercialize this agent outside Greater China and certain Asian countries under the code EP0031.

In March 2024, it was announced that EP0031/A400 was granted Fast Track designation by the Food and Drug Administration (FDA) for the treatment of RET-fusion positive NSCLC. In April 2024, EP0031/A400 was cleared by the FDA to progress into Phase 2 clinical development and is now open in the United States, United Kingdom, Europe and United Arab Emirates.

On September 22, 2025 Akeso Inc. (9926.HK) reported that the Late-Breaking Abstract (LBA) from the registrational Phase III clinical study (AK112-306/HARMONi-6 study) of ivonescimab, a globally first-in-class bispecific antibody targeting PD-1 and VEGF, will be presented at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress (Press release, Akeso Biopharma, SEP 22, 2025, View Source [SID1234656155]). This study, which evaluates ivonescimab in combination with chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC), has been selected for the Presidential Symposium. The study’s principal investigator, Professor Lu Shun, Director of the Department of Oncology at Shanghai Chest Hospital, will present the results from this pivotal study.

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Additionally, the final results of the Phase III clinical study (COMPASSION-15/AK104-302 study) of cadonilimab in combination with oxaliplatin and capecitabine as first-line treatment for unresectable, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, have been accepted for a Mini Oral Session at ESMO (Free ESMO Whitepaper). Cadonilimab is a first-in-class bispecific antibody targeting PD-1 and CTLA-4 developed by Akeso that is currently approved for first line treatment of gastric cancer, first line treatment of cervical cancer, and second/third line treatment of cervical cancer. The study’s principal investigator, Professor Shen Lin from Peking University Cancer Hospital, will present the findings in an oral presentation.

Phase Ⅲ Study of lvonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as Firstline Treatment for advanced squamous non-small cell lung cancer (HARMONi-6)

Speakers: Professor Shun Lu (Shanghai, China)
Session: Presidential Symposium 2 Proffered Paper session
Presentation Time: 16:30 -16:42 (CEST) Sun. 19.10.2025
Room: Berlin Auditorium – Hub 27
The upcoming detailed results from the HARMONi-6 study, to be presented at ESMO (Free ESMO Whitepaper) 2025, will provide a comprehensive overview of the exceptional efficacy and favorable safety profile of ivonescimab in combination with chemotherapy for the treatment of first line advanced squamous NSCLC. These findings will further underscore ivonescimab’s role in advancing treatment strategies beyond first-generation immuno-oncology therapies.

The HARMONi-6 study represents the third Phase III trial of ivonescimab in NSCLC, showing significant positive outcomes. This trial is particularly important as it introduces an antiangiogenic mechanism-based therapy for sq-NSCLC, a subtype previously lacking such therapeutic options. Notably, it is the second Phase III head-to-head trial where ivonescimab has outperformed a PD-1 inhibitor-based regimen, reinforcing its breakthrough clinical value.

The promising results thus far affirm that ivonescimab provides significant advancements in clinical treatment for NSCLC, whether compared to PD-1 monotherapy, PD-1 plus chemotherapy, or VEGF-targeted therapies. The consistent superiority observed in these comparisons highlights ivonescimab’s potential to redefine treatment paradigms in oncology.

In April 2025, Akeso announced that the topline results from the registrational Phase III study, HARMONi-6, met its primary endpoint of progression-free survival (PFS), as confirmed by the Independent Data Monitoring Committee (IDMC). The results showed statistically significant and clinically meaningful improvements in PFS for ivonescimab plus chemotherapy compared to tislelizumab plus chemotherapy. In the intent-to-treat (ITT) population, patients receiving ivonescimab plus chemotherapy showed significantly superior PFS benefits compared to the control group. This PFS improvement was consistently observed across all subgroups, regardless of PD-L1 expression status.

On July 28, 2025, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) accepted the supplemental New Drug Application (sNDA) for ivonescimab in combination with chemotherapy as a first-line treatment for advanced sq-NSCLC.

Cadonilimab (Cado) plus chemotherapy (chemo) versus chemotherapy as first-line (1L) treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: final results of the Phase Ⅲ COMPASSION-15 trial
Speaker: Professor Shen Lin, Peking University Cancer Hospital
Presentation Format: Mini Oral Session
Abstract Number: 2098MO
Presentation Time: 10:45–10:50 AM (CEST) , Saturday, 18 October 2025
The final results of the COMPASSION-15 study, to be presented at ESMO (Free ESMO Whitepaper) 2025, will further validate the groundbreaking clinical value of the cadonilimab-based regimen, reinforcing its potential as a transformative therapeutic option for advanced gastric cancer.

Preliminary findings from the COMPASSION-15 study were first presented by Professor Ji Jiafu of Peking University Cancer Hospital at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. These results garnered international recognition and were subsequently published in the esteemed Nature Medicine journal. Due to the positive clinical results, cadonilimab received approval from the NMPA in September 2024 for the first-line treatment of advanced gastric cancer. Furthermore, the regimen was included as the only immunotherapy strategy with a Category I Recommendation (Level IA Evidence) in the 2025 CSCO Gastric Cancer Guidelines, facilitating its widespread adoption in clinical practice.

On September 22, 2025 Akeso Inc. (9926.HK) reported that the Late-Breaking Abstract (LBA) from the registrational Phase III clinical study (AK112-306/HARMONi-6 study) of ivonescimab, a globally first-in-class bispecific antibody targeting PD-1 and VEGF, will be presented at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress (Press release, Akeso Biopharma, SEP 22, 2025, View Source [SID1234656155]). This study, which evaluates ivonescimab in combination with chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC), has been selected for the Presidential Symposium. The study’s principal investigator, Professor Lu Shun, Director of the Department of Oncology at Shanghai Chest Hospital, will present the results from this pivotal study.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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

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Additionally, the final results of the Phase III clinical study (COMPASSION-15/AK104-302 study) of cadonilimab in combination with oxaliplatin and capecitabine as first-line treatment for unresectable, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, have been accepted for a Mini Oral Session at ESMO (Free ESMO Whitepaper). Cadonilimab is a first-in-class bispecific antibody targeting PD-1 and CTLA-4 developed by Akeso that is currently approved for first line treatment of gastric cancer, first line treatment of cervical cancer, and second/third line treatment of cervical cancer. The study’s principal investigator, Professor Shen Lin from Peking University Cancer Hospital, will present the findings in an oral presentation.

Phase Ⅲ Study of lvonescimab plus chemotherapy versus Tislelizumab plus chemotherapy as Firstline Treatment for advanced squamous non-small cell lung cancer (HARMONi-6)

Speakers: Professor Shun Lu (Shanghai, China)
Session: Presidential Symposium 2 Proffered Paper session
Presentation Time: 16:30 -16:42 (CEST) Sun. 19.10.2025
Room: Berlin Auditorium – Hub 27
The upcoming detailed results from the HARMONi-6 study, to be presented at ESMO (Free ESMO Whitepaper) 2025, will provide a comprehensive overview of the exceptional efficacy and favorable safety profile of ivonescimab in combination with chemotherapy for the treatment of first line advanced squamous NSCLC. These findings will further underscore ivonescimab’s role in advancing treatment strategies beyond first-generation immuno-oncology therapies.

The HARMONi-6 study represents the third Phase III trial of ivonescimab in NSCLC, showing significant positive outcomes. This trial is particularly important as it introduces an antiangiogenic mechanism-based therapy for sq-NSCLC, a subtype previously lacking such therapeutic options. Notably, it is the second Phase III head-to-head trial where ivonescimab has outperformed a PD-1 inhibitor-based regimen, reinforcing its breakthrough clinical value.

The promising results thus far affirm that ivonescimab provides significant advancements in clinical treatment for NSCLC, whether compared to PD-1 monotherapy, PD-1 plus chemotherapy, or VEGF-targeted therapies. The consistent superiority observed in these comparisons highlights ivonescimab’s potential to redefine treatment paradigms in oncology.

In April 2025, Akeso announced that the topline results from the registrational Phase III study, HARMONi-6, met its primary endpoint of progression-free survival (PFS), as confirmed by the Independent Data Monitoring Committee (IDMC). The results showed statistically significant and clinically meaningful improvements in PFS for ivonescimab plus chemotherapy compared to tislelizumab plus chemotherapy. In the intent-to-treat (ITT) population, patients receiving ivonescimab plus chemotherapy showed significantly superior PFS benefits compared to the control group. This PFS improvement was consistently observed across all subgroups, regardless of PD-L1 expression status.

On July 28, 2025, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) accepted the supplemental New Drug Application (sNDA) for ivonescimab in combination with chemotherapy as a first-line treatment for advanced sq-NSCLC.

Cadonilimab (Cado) plus chemotherapy (chemo) versus chemotherapy as first-line (1L) treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: final results of the Phase Ⅲ COMPASSION-15 trial
Speaker: Professor Shen Lin, Peking University Cancer Hospital
Presentation Format: Mini Oral Session
Abstract Number: 2098MO
Presentation Time: 10:45–10:50 AM (CEST) , Saturday, 18 October 2025
The final results of the COMPASSION-15 study, to be presented at ESMO (Free ESMO Whitepaper) 2025, will further validate the groundbreaking clinical value of the cadonilimab-based regimen, reinforcing its potential as a transformative therapeutic option for advanced gastric cancer.

Preliminary findings from the COMPASSION-15 study were first presented by Professor Ji Jiafu of Peking University Cancer Hospital at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. These results garnered international recognition and were subsequently published in the esteemed Nature Medicine journal. Due to the positive clinical results, cadonilimab received approval from the NMPA in September 2024 for the first-line treatment of advanced gastric cancer. Furthermore, the regimen was included as the only immunotherapy strategy with a Category I Recommendation (Level IA Evidence) in the 2025 CSCO Gastric Cancer Guidelines, facilitating its widespread adoption in clinical practice.

On September 22, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that the Company received notice of an additional advance payment from the Cancer Prevention and Research Institute of Texas (CPRIT), the second-largest public cancer research funder globally (Press release, Plus Therapeutics, SEP 22, 2025, View Source;_hsenc=p2ANqtz-9FE0VkS0lXyVYLeYUX_e8OPwY_tMBw4qcG1ikTgGaPNR7TS1e_6ZHFTELAxFZVszjULgsem3LXhrctDaOQfJKZLO2kJw&_hsmi=381576755&utm_content=381576755&utm_source=hs_email [SID1234656154]). This $1.9 million payment is part of the Company’s previously awarded $17.6 million grant and is the second non-dilutive financing received from CPRIT following the $1.6 million receipt announced in July 2025.

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"Continued payments from CPRIT are supportive to our radiotherapeutic development initiatives, with a further $1.9 million in funding expected over the next 12 months, providing a steady source of significant non-dilutive financing," said Andrew Sims, Plus Therapeutics Chief Financial Officer. "The support from CPRIT builds on our active National Institutes of Health and Department of Defense grants, reflecting strong commitment for our clinical programs from strategic institutions. We continue to actively pursue additional grant opportunities to strengthen our capital position."

The funding supports and accelerates the Company’s clinical development of REYOBIQ for the ReSPECT-LM dose optimization trial and further develops the Company’s CNSide LM diagnostic test as a key pivotal trial endpoint.

About LM
Leptomeningeal metastases (LM) are a rare but severe complication of advanced cancer, affecting the fluid-lined structures of the central nervous system. LM occurs in approximately 5% of patients with metastatic cancer, with breast cancer, lung cancer, and melanoma being the most common sources. Median survival is typically 2-6 months, and effective treatment options are limited, highlighting the urgent need for novel therapies.

About REYOBIQ (rhenium Re186 obisbemeda)
REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy specifically formulated to deliver direct targeted high dose radiation in CNS tumors in a safe, effective, and convenient manner to optimize patient outcomes. REYOBIQ has the potential to reduce off target risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue, and gamma energy for real-time imaging. REYOBIQ is being evaluated for the treatment of recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer in the ReSPECT-GBM, ReSPECT-LM, and ReSPECT-PBC clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT). The Company’s ReSPECT-PBC clinical trial for pediatric brain cancer is supported by a $3 million grant from the U.S. Department of Defense’s Peer Reviewed Cancer Research Program.