Cabozantinib (s)-Malate

5月16日，中国国家药监局药品审评中心（CDE）公示将和誉医药的ABSK-011胶囊（通用名：依帕戈替尼/Irpagratinib）纳入突破性治疗品种，拟用于治疗既往接受过免疫检查点抑制剂（ICI）和多靶点酪氨酸激酶抑制剂（mTKI）治疗失败的FGF19过表达晚期肝细胞癌患者。疗效数据上，作为全球首个针对FGF19/FGFR4信号通路异常激活的小分子抑制剂，它在2023年ESMO年会上公布的Ib期数据就让人眼前一亮：每日两次给药组的27例患者中，客观缓解率（ORR）达到40.7%，其中包括1例完全缓解和10例部分缓解，中位无进展生存期（PFS）5个月。横向对比的话，现有肝癌二线治疗药物如瑞戈非尼、卡博替尼的ORR通常不足15%，而诺华此前开发的同类FGFR4抑制剂在临床试验中ORR仅有16%。当它与PD-L1抑制剂阿替利珠单抗联用时，2024年ESMO-GI大会上更新的II期数据显示ORR进一步提升至50%，甚至在既往接受过免疫治疗的患者中依然有效。这可能为肝癌一线治疗打开新局面。安全性方面，患者最常见的不良反应是可控的腹泻、乏力，没有出现FGFR抑制剂常见的皮肤毒性或高磷血症。FGF19过表达这个生物标志物的应用，直接把目标锁定在约占肝癌患者30%的特定人群。和誉医药从早期研究就与国内顶尖临床中心合作，比如武汉同济医院陈孝平院士团队牵头推进的全国多中心研究，不仅验证了FGF19检测的临床价值，还建立起标准化的检测流程。先锁定生物标志物，再开发药物既避免了传统肝癌治疗“大水漫灌”的低效，又为后续伴随诊断的商业化铺平道路。值得一提的是，入组患者必须同时满足“接受过ICI和mTKI治疗失败”的条件，这相当于精准切入末线治疗空白市场，要知道，这类患者的中位生存期往往不足6个月，现有治疗手段几乎束手无策。不过，依帕戈替尼的研发过程并非一帆风顺。FGFR4这个靶点曾让多家跨国药企折戟沉沙。诺华早期的候选药物因严重骨骼毒性终止开发，Blueprint公司的BLU-554也因疗效未达预期暂停临床。和誉医药能后来居上，关键在于分子设计上的突破。研发团队通过上千次实验筛选出高选择性化合物，成功避免了对FGFR1-3的脱靶效应，这正是此前竞品失败的主因。从商业策略看，企业针对ICI/mTKI治疗失败的患者群体快速推进注册临床，同时与罗氏合作探索与阿替利珠单抗联用的一线治疗方案，这既能快速满足临床急需，又为后续市场扩张埋下伏笔。当然，机遇也很重要。政策层面，2024年4月FDA授予的孤儿药资格为其打开美国市场提供快速通道，7年市场独占期和税收优惠显著降低商业化成本。国内CDE的突破性治疗认定更是雪中送炭，根据既往案例，纳入该程序的药物平均审评周期可缩短6-8个月。考虑到中国每年新发肝癌病例占全球55%，且约半数患者存在FGF19过表达，这个近30万人的潜在市场足以让依帕戈替尼站稳脚跟。但是，FGF19检测的普及度直接影响药物可及性，目前全国能开展标准化检测的三甲医院不足百家，基层医疗机构几乎空白；此外，约20%患者在治疗6个月后出现FGFR4耐药突变，这和EGFR-TKI面临的困境如出一辙。为此，和誉医药已启动新一代抑制剂ABSK-012的临床试验，试图通过序贯治疗延长药物生命周期。放眼全球竞争格局，依帕戈替尼正处于前有堵截后有追兵的关键期。虽然目前尚无同类药物获批，但Blueprint公司重启的BLU-554改良版已进入II期临床，诺华也通过收购获得新一代FGFR4抑制剂权益。更不可忽视的是跨国药企在联合治疗领域的深厚积累，罗氏自家就有PD-L1抑制剂和抗血管生成药物的组合方案，未来是否会将依帕戈替尼纳入生态体系尚存变数。不过从现有数据看，中国药企这次确实跑在了前面：依帕戈替尼的临床进展比国际竞品快至少12个月，且40.7%的ORR暂时领跑赛道。若能顺利在2026年上市，它有望成为首个针对FGF19/FGFR4通路的肝癌靶向药，改写NCCN等国际指南的推荐等级。信息来源：［1］https://www.sohu.com/a/893366006_100169898［2］http://wtt.xianjichina.com/forum/details_548383药事纵横投稿须知：稿费已上调，欢迎投稿

Approval based on results from the CheckMate-77T trial which showed perioperative Opdivo improved event-free survival compared to neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo Opdivo is now the only PD-(L)1 inhibitor approved for both perioperative and neoadjuvant-only treatment of resectable non-small cell lung cancer in the European Union PRINCETON, NJ, USA I May 16, 2025 I Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved the perioperative regimen of neoadjuvant Opdivo ® (nivolumab) and chemotherapy followed by surgery and adjuvant Opdivo for the treatment of resectable non-small cell lung cancer (NSCLC) at high risk of recurrence in adult patients whose tumors have PD-L1 expression ≥1%. $BMY announces the European Commission has approved its perioperative #immunotherapy-based regimen for certain patients with resectable non-small cell #lungcancer. Share “This approval brings another perioperative immunotherapy treatment option for select patients with resectable NSCLC in the EU, helping address an ongoing need for interventions that can meaningfully reduce the risk of cancer returning after initial therapy,” said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. “With this approval, Opdivo with chemotherapy followed by adjuvant Opdivo has the potential to change the course of certain patients’ disease by significantly reducing the risk of cancer recurrence and improving long-term outcomes earlier in the treatment journey.” The decision is based on results from the CheckMate -77T study, which evaluated the perioperative regimen of neoadjuvant Opdivo with platinum-doublet chemotherapy followed by surgery and adjuvant Opdivo monotherapy, compared to neoadjuvant platinum-doublet chemotherapy and placebo followed by surgery and adjuvant placebo in adult patients with resectable NSCLC. The trial met its primary endpoint of event-free survival (EFS), showing that the risk of disease recurrence, progression or death was reduced by 42% (EFS Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.43 to 0.78; P=0.00025) in patients treated in the Opdivo arm, compared to the chemotherapy and placebo arm, after a median follow-up of 25.4 months. Furthermore, after 24–months, EFS was observed in 65% of patients in the Opdivo arm, compared to 44% of patients in the chemotherapy and placebo arm. The trial also demonstrated clinically meaningful improvements in the secondary efficacy endpoints of pathologic complete response (pCR) and major pathologic response (MPR). The regimen benefit was demonstrated across all efficacy endpoints and in all randomized subjects. Additionally, the safety profile of the perioperative regimen was consistent with previously reported studies in NSCLC. No new safety signals were identified. The EFS, pCR and MPR results from the CheckMate -77T trial were first presented at the European Society of Medical Oncology (ESMO) Congress 2023 and published in The New England Journal of Medicine . Updated results were presented at the ESMO Congress 2024. CheckMate -77T is ongoing to assess the key secondary endpoint of overall survival (OS). This approval by the EC for the treatment of resectable NSCLC at high risk of recurrence in adult patients whose tumors have PD-L1 expression ≥1% is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approvals in lung cancer, Opdivo- based options are also approved for treatment of multiple tumor types in the EU. In October 2024, the CheckMate -77T trial was used as the basis for the U.S. Food and Drug Administration’s (FDA) approval of Opdivo for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, for neoadjuvant treatment, in combination with platinum-doublet chemotherapy, followed by single-agent Opdivo as adjuvant treatment after surgery. Bristol Myers Squibb thanks the patients and investigators for their significant contributions to the Phase 3 CheckMate -77T clinical trial. About CheckMate -77T CheckMate -77T is a Phase 3 randomized, double-blind, placebo-controlled, multi-center trial evaluating neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo versus neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant placebo in 461 patients with resectable stage IIA to IIIB NSCLC. The primary endpoint of the trial is EFS. Secondary endpoints include OS, pCR and MPR. About Lung Cancer Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes. About Opdivo Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo ’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression. In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union . INDICATIONS OPDIVO ® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO ® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. OPDIVO ® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC). OPDIVO ® (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO ® as adjuvant treatment after surgery. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). OPDIVO ® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO ® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO ® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). OPDIVO ® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO ® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO ® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO ® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Please see U.S. Full Prescribing Information for OPDIVO and YERVOY Clinical Trials and Patient Populations Checkmate 9DW – hepatocellular carcinoma, in combination with YERVOY; Checkmate 227—previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY, after prior treatment with sorafenib; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer in combination with YERVOY; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma in combination with chemotherapy; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066—previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 77T–Neoadjuvant treatment with platinum-doublet chemotherapy for non-small cell lung cancer followed by single-agent OPDIVO as adjuvant treatment after surgery; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , X , YouTube , Facebook and Instagram . SOURCE: Bristol Myers Squibb