This phase II trial tests how well zipalertinib with carboplatin and pemetrexed works in treating stage II-IIIB non small cell lung cancer. that can be removed by surgery (resectable). Zipalertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving zipalertinib with carboplatin and pemetrexed may kill more tumor cells in patients with resectable, stage II-IIIB non-small cell lung cancer.

开始日期2027-06-01

申办/合作机构

Jonsson Comprehensive Cancer Center

[+1]

NCT07720167

/ Not yet recruiting临床2期

Neoadjuvant Chemo-Cemiplimab for Clinical Stage I, 2-3.9cm, Non-Small Cell Lung Cancer

The study will investigate the role of cemiplimab in combination with platinum doublet chemotherapy in stage I resectable non-small cell lung cancer (NSCLC). Sub-4cm NSCLC tumors are highly lethal malignancies, yet no therapies are used in these patients to improve chances of survival with surgery alone. Here will be examined the ability of 3 cycles of cemiplimab-chemotherapy to induce pathologic complete responses to treatment.

开始日期2026-11-01

申办/合作机构

The Medical University of South Carolina

NCT07234877

/ Not yet recruiting临床2期IIT

A Randomized Phase II Study Evaluating Upfront SRT to All Brain Metastases Followed by Ivonescimab Plus Chemotherapy Versus Upfront Ivonescimab Plus Chemotherapy in Patients With Asymptomatic Active Brain Metastases From NSCLC

This is a randomized, two-arm, comparative Phase II clinical trial designed to evaluate the difference in intracranial progression-free survival (iPFS) between two treatment strategies, assessed locally.
Approximately 158 patients will be randomized in a 1:1 ratio. Will be included patients with pathology proven metastatic NSCLC without an actionable genomic alteration for which there is first line targeted treatment available and active asymptomatic brain metastasis (newly diagnosed or progressive).
The primary objective is to compare iPFS between the two arms.

开始日期2026-11-01

申办/合作机构

European Organisation for Research & Treatment of Cancer

[+1]

100 项与培美曲塞二钾相关的临床结果

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100 项与培美曲塞二钾相关的转化医学

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100 项与培美曲塞二钾相关的专利（医药）

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4,288

项与培美曲塞二钾相关的文献（医药）

2026-12-31·JOURNAL OF MEDICAL ECONOMICS

Cost comparison of osimertinib plus platinum-pemetrexed versus amivantamab plus lazertinib for the first-line treatment of patients with locally advanced or metastatic epidermal growth factor receptor-mutated non-small cell lung cancer

Article

作者: Hearmon, Natalie ; Upton, Elysia ; Procter, Emily ; Nieva, Jorge J. ; Rattigan-Brown, Yanique ; Freeman, Harry ; Lopes, Gilberto de Lima ; Karia, Pritesh

OBJECTIVES:

Novel first-line (1L) combination regimens offer improved efficacy for patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) versus the standard of care, but their costs have not been comprehensively evaluated. Total and differential costs of 1L osimertinib plus platinum-pemetrexed, intravenous (IV) amivantamab plus lazertinib, and subcutaneous (SC) amivantamab plus lazertinib were estimated from a United States (US) payer perspective.

METHODS:

A cost of care model was developed to assess treatment acquisition, administration, disease management, and adverse event (AE) management costs for osimertinib plus platinum-pemetrexed versus IV and SC amivantamab plus lazertinib for patients with EGFRm NSCLC. A one-year time horizon was chosen to allow for direct treatment comparison; a one-year treatment duration was assumed for treat-to-progression regimen components.

RESULTS:

The total first-year cost per-patient for osimertinib plus platinum-pemetrexed (all-payer perspective: $172,600; private perspective: $253,529; Medicare perspective: $84,926) was over twofold lower than for IV amivantamab plus lazertinib (all-payer perspective: $418,176; private perspective: $618,240; Medicare perspective: $201,441) and for SC amivantamab plus lazertinib (all-payer perspective: $419,718; private perspective: $621,166; Medicare perspective: $201,482). This translated to per-patient cost savings of $245,577; $364,711; and $116,514 for osimertinib plus platinum-pemetrexed versus IV amivantamab plus lazertinib and $247,118; $367,637; and $116,555 versus SC amivantamab plus lazertinib for the all-payer, private, and Medicare perspectives, respectively.

LIMITATIONS:

Limited data availability necessitated cost conversions across payer perspectives and assumptions for select inputs, including specific concomitant medication durations. Additionally, as any payer-negotiated discounts for treatment are confidential, model treatment acquisition costs reflected list prices. These data limitations contributed to uncertainty surrounding model inputs.

CONCLUSIONS:

From a US payer perspective, osimertinib plus platinum-pemetrexed was associated with substantially lower overall costs compared with IV and SC amivantamab plus lazertinib for the 1L treatment of patients with EGFRm locally advanced or metastatic NSCLC.

2026-10-01·INTERNATIONAL IMMUNOPHARMACOLOGY

Pemetrexed potentiates γδ T cell-based immunotherapy in NSCLC through ATM-STING-NF-κB-mediated induction of NKG2D ligands

Article

作者: Fang, Hsin-Yuan ; Huang, Kevin Chih-Yang ; Chen, Mei-Chih ; Chen, Yi-Wen ; Kan, Kai-Wen ; Li, Yu-Hsuan ; Chiu, Shao-Chih ; Cho, Der-Yang ; Hung, Meng-Yu ; Pan, Chih-Ming ; Huang, Shi-Wei ; Lin, Ho

Adoptive T-cell therapy is a promising strategy for cancer immunotherapy; however, its efficacy is often limited by the immunosuppressive tumor microenvironment. γδ T cells, particularly the Vγ9Vδ2 subset, exhibit innate-like cytotoxicity and are emerging candidates for adoptive immunotherapy. Pemetrexed, an antifolate chemotherapeutic agent, has documented immunomodulatory effects in αβ T-cell settings; however, its impact on γδ T-cell antitumor responses remains insufficiently defined. Here, Vγ9Vδ2 T cells were isolated and expanded from healthy-donor peripheral blood mononuclear cells (PMBCs) and co-cultured with non-small cell lung cancer (NSCLC) cells with or without pemetrexed pretreatment. Pemetrexed significantly enhanced γδ T cell-mediated cytotoxicity compared with either treatment alone. Mechanistically, pemetrexed increased the expression of NKG2D ligands, including MHC class I chain-related proteins A/B (MICA/B) and UL16-binding proteins (ULBPs), through the ataxia-telangiectasia mutated (ATM)-stimulator of interferon genes (STING)-nuclear factor-κB (NF-κB) signaling axis. ATM activation triggered cyclic GMP-AMP synthase-independent STING signaling and preferentially activated NF-κB rather than interferon regulatory factor 3 (IRF3), thereby promoting transcriptional upregulation of NKG2D ligands and improving tumor recognition by γδ T cells. Consistent with the cell-line findings, pemetrexed increased MICA/B and ULBP2/5/6 expression in NSCLC patient-derived organoids. Furthermore, in an in vivo NSCLC animal model, combined pemetrexed and adoptive γδ T-cell therapy suppressed tumor growth more effectively than either treatment alone and was accompanied by increased NKG2D ligand expression. Collectively, these findings reveal a tumor-sensitizing mechanism by which pemetrexed potentiates γδ T-cell antitumor function and support combining pemetrexed with γδ T cell-based immunotherapy for NSCLC.

2026-09-01·JOURNAL OF CLINICAL NEUROSCIENCE

Update on the management of leptomeningeal disease in solid organ malignancy: Systemic, intrathecal and novel therapies

Review

作者: Dimou, James ; Campbell, Bethany ; Topp, Monique ; Hovens, Chris ; Fisher, Sanlin ; Airth, Angus ; Stylli, Stan

BACKGROUND:

Leptomeningeal disease (LMD) is an increasingly recognised late-stage complication of solid tumours (primarily melanoma, lung and breast cancers). It involves dissemination to the leptomeninges surrounding the brain and spinal cord and carries a poor prognosis ranging from 2-6 months. Recent advances in emerging therapies such as CNS-active targeted therapy, intrathecal agents, and early-phase immunotherapy necessitate an updated appraisal of prospective data.

METHODS:

A systematic search of MEDLINE, Embase, Scopus and CENTRAL (January 2020-July 2025) was undertaken according to PRISMA 2020 guidelines (PROSPERO CRD420251181223). Prospective clinical studies evaluating systemic, intrathecal, or novel therapies for adult solid-tumour LMD were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), response rates, neurological function, quality of life (QoL) and safety. Risk of bias was assessed using the Newcastle-Ottawa Scale or Cochrane RoB-2 as appropriate.

RESULTS:

Ten prospective trials (n = 520) met study inclusion criteria. Two Korean phase II studies demonstrated consistent intracranial activity of osimertinib in EGFR-mutant NSCLC-LMD, with median OS 13-15 months and intracranial ORR 51.6% by blinded RANO-LMD review. Three phase I/II Chinese trials of IT pemetrexed showed reproducible disease-control signals (ORR 43.5-80.3%, median OS 9-12 months) with frequent neurological improvement and predominantly reversible myelosuppression. In breast-cancer LMD, IT liposomal cytarabine improved LM-PFS (3.8 vs 2.2 months) without a significant OS or QoL advantage. IT trastuzumab produced modest responses with acceptable tolerability, while combined IT/IV nivolumab in melanoma LMD showed feasibility and manageable toxicity. BLOSSOM was the only study to demonstrate QoL improvement, while DEPOSEIN collected EORTC-based QoL data but found no between-arm differences; QoL reporting in other trials was minimal or absent.

CONCLUSIONS:

Contemporary prospective evidence suggests incremental outcome gains in solid-tumour LMD, driven by CNS-active targeted therapy (osimertinib) and, in selected cases, IT pemetrexed. However, reliance on single-arm designs, heterogeneous endpoints, and sparse QoL data reduces confidence in the findings. Standardised LMD-specific outcomes and controlled comparative trials are needed to define best practice.

348

项与培美曲塞二钾相关的新闻（医药）

2026-08-26

·十亿分子

WCLC 2026 前瞻：双抗、ADC 与小分子重塑肺癌治疗格局

每年一届的世界肺癌大会（WCLC）都是全球肺癌药物研发的「风向标」。今年 9/12 日 WCLC 的前瞻摘要已经发布，本公众号初步梳理出了 420 条摘要，其中 169 条披露了临床疗效或安全性数据。阅读之后，给人的初步印象：双抗/多抗与 ADC 正从「概念验证」全面走向「改写标准治疗」，小分子则在罕见靶点与耐药场景继续「精雕细琢」。以下是看完摘要后的整体印象，后续本公众号将进一步跟进感兴趣的研发药物精细分析。一、双抗/三抗：免疫治疗的「下半场」，比的是谁先拿到 OS 免疫检查点抑制剂的白热化竞争，PD-1×VEGF 双特异性抗体扎堆出现，三抗临床数据也进一步增加。本届双抗的两大值得高度关注的方向无疑是：同时靶向免疫+血管的「1+1」组合，以及三靶点免疫协同临床数据。 ① PD-1×VEGF 双抗成为「抗血管+免疫」的集大成者。ivonescimab（PD-1×VEGF）在 HARMONi 全球 III 期研究中，针对三代 EGFR-TKI 耐药后的 EGFR 突变晚期 NSCLC：联合组中位 OS 16.8 个月 vs 安慰剂+化疗 14.0 个月，HR 0.76（95%CI 0.61–0.95），nominal P=0.0151，是首个在该场景带来生存获益的双抗；≥3 级 TRAE 51.4% vs 43.6%，安全性整体可控。国产 RC148（PD-1×VEGF）一线治疗鳞状 NSCLC：10 mg/kg 组 ORR 达 90.0%，其中 PD-L1 阴性亚组 93.3%，mPFS 10.8 个月，差异化卡位 PD-L1 阴性人群。 ② EGFR 突变「双抗+TKI」成主流打法。amivantamab（EGFR×c-MET）联合 lazertinib（EGFRi）在 AMIGO-1 研究中达成主要终点：18 个月 PFS 66.7%（80%CI 57.5–74.4，p=0.0045），中位 PFS 25.1 个月；MARIPOSA 进一步显示其对比 osimertinib（EGFR T790M）带来 OS 延长（HR 0.75，P=0.005）。在 EGFR 敏感突变一线趋饱和的背景下，双抗+TKI 正争夺「更长的生存」。 ③ CTLA-4×PD-1 双抗：围手术期与一线「抢滩」。cadonilimab（CTLA-4×PD-1）围手术期化疗 pCR 28.9%、MPR 52.6%，不可切除 III 期同步放化疗后 1 年 PFS1 69.2%、ORR 85.4%；Opamtistomig（PD-L1×4-1BB）（LBL-024）一线联合化疗 ORR 65.0%（PD-L1≥1% 亚组 78.3%）；Rilvegostomig（PD-1×TIGIT）在 PD-L1≥50% 队列确认 ORR 61.8%、mPFS 16.7 个月、24 个月 OS 率 67.6%；JS207（PD-1×VEGF）新辅助 pCR 54.5%、MPR 72.7%。 ④ PD-1×CTLA-4×VEGF 三抗：把「双免疫 + 抗血管」装进一个分子。相比双抗，三抗致力于在一个分子上同时拮抗 CTLA-4（免疫启动）、PD-1（免疫效应）与 VEGF（血管微环境去抑）。本届 WCLC 2026 亮相的 HC010（PD-1×CTLA-4×VEGF）（宏成/倍特）公布了首次人体 Phase I：69 例可评估 ORR 14.5%、DCR 71%，其中免疫治疗难治性 NSCLC 亚组 ORR 25%、DCR 75%，最优剂量组（31 例）呈趋势更好；≥3 级 TRAE 24.1%，常见为皮疹 38.0%（G3 1.3%）、甲减 22.8%、AST/ALT 及贫血各 20.3%。同一靶点的 CS2009（PD-1×CTLA-4×VEGF）（基石）走得更远：已入组近 300 例、POC 落地，一线 PD-L1 高表达 ORR 81.3%、后线 IO 耐药 NSCLC ORR 30.8%，III 期 MRCT 计划 2026 年底启动。二、ADC 浪潮：靶点扩张 +「双抗 ADC」本届 ADC 的核心变化是：从广谱表达的「泛癌种靶点」（TROP2/HER2/HER3 等，靠适应症广取胜），走向肿瘤选择性更强的「精准靶点」（DLL3/SEZ6 等）与「双抗 ADC」，以拓宽治疗窗、降低靶向脱靶毒性，并加速向 SCLC、罕见病理类型渗透。 ① 双抗 ADC 登场。ALK202（EGFR×c-MET 双抗 ADC）在 EGFR 突变非鳞 NSCLC 中，高剂量组 ORR 42.9%、DCR 92.9%，3.2 mg/kg D1/D8 组 ORR 50%、DCR 100%——把双抗的「协同内吞」与 ADC 的「精准杀伤」结合。≥3 级 TRAE 65.8%，血液学毒性仍是主要约束。 ② TROP2 赛道：疗效分化，亚组深挖。sacituzumab tirumotecan（TROP2，sac-TMT）在高肿瘤负荷（≥3 转移灶）亚组显著获益：mOS 未达到 vs 化疗 15.7 个月（HR 0.49），18 个月 OS 率 63.4% vs 37.6%，ORR 61.7% vs 43.7%；在其他可操作基因组改变（AGA）人群 ORR 34.4%、中位 DOR 12.7 个月。 ③ 小细胞肺癌成 ADC 新蓝海。ABBV-706（SEZ6）治疗复发/难治 SCLC，既往数据 ORR 52%、mOS 11.3 个月，本次主要报告肺炎/ILD 4.2%；ifinatamab deruxtecan（B7-H3，I-DXd）在经治 ES-SCLC 疗效良好，ILD/肺炎 13.1%；YL201（B7-H3 ADC）联合 serplulimab（PD-1）一线 ES-SCLC 达 cORR 85.4%、mPFS 12.9 个月。tarlatamab（DLL3×CD3）在神经内分泌肿瘤取得 ORR 30%、CRS 80% 但均为 1–2 级。三、小分子精准治疗：罕见靶点与「耐药破局」并进在双抗与 ADC 之外，小分子依旧是驱动基因阳性肺癌的「底座」。本届在 EGFR、ALK/ROS1、KRAS、MET，以及四代 TKI/耐药后场景均密集发布数据，方向可归纳为四点：更优的生存、更广的罕见靶点、更强的大脑穿透、以及对抗耐药的「精准复合」。 ① EGFR-TKI：三代「内卷」，脑转移与联合成为胜负手。一线 befotertinib（EGFR） mPFS 22.0 个月 vs icotinib（EGFR） 13.8 个月（HR 0.52）；lazertinib（EGFR） mPFS 22.1 个月（Del-19 25.5 vs L858R 16.6 个月）；osimertinib（EGFR T790M）+ bevacizumab（VEGF-A） mPFS 19.8 vs 12.6 个月（HR 0.528）。脑转移是主场：furmonertinib（EGFR）颅内 ORR 85.4%、颅内 PFS 24.0 个月，联合 pemetrexed（化疗）后颅内 ORR 84%；osimertinib（EGFR T790M）+ savolitinib（MET）（MET 共突变，FLOWERS）mPFS 22.6 vs 单药 11.2 个月。 ② ALK/ROS1：生存竞速与「全程管理」。lorlatinib（ALK/ROS1） CROWN 7 年随访，mPFS 至今仍未达到 vs crizotinib（ALK/ROS1/c-MET） 9.1 个月，二次进展 PFS（PFS2）HR 0.43；taletrectinib（ROS1） TKI 初治 cORR 89.8%、mPFS 46.1 个月，经治 cORR 55.8%，覆盖既往耐药；alectinib（ALK）新辅助 MPR 55.8%、pCR 18.6%；ficonalkib（ALK）颅内 ORR 65.0% 且无神经毒性，向脑转移 ALK+ 人群延伸。 ③ KRAS：从 G12C 走向 G12D，「分子缓解」成新标尺。GFH375（KRAS G12D） ORR 54.7%、确认 ORR 49.1%、mPFS 8.1 个月，是 G12D 抑制剂中少见的具临床意义数据；adebrelimab（PD-L1）+ HS-10370（KRAS G12C）一线 ORR 87.0%、12 个月 PFS 率 80.2%；garsorasib（KRAS G12C）+ sitneprotafib（SHP2）以 ctDNA 动态分层，93.3% 基线阳性者于 C3D1 实现清除，未清除者 PFS 缩短至 4.3 个月——「分子缓解」正成为早期判断疗效的重要代理终点。 ④ MET 与罕见突变：精准「扩目录」。vebreltinib（c-MET）（MET 扩增）ORR 66.7–73.3%、mPFS 12.0–13.6 个月；osimertinib（EGFR T790M）+ vebreltinib（c-MET）（MET 共突变）mPFS 32.8 个月、确认 ORR 53.3%；dacomitinib（EGFR/HER2）治疗罕见 EGFR 突变 ORR 80%、mPFS 14.3 个月、mOS 44.2 个月。 ⑤ 耐药破局：四代 TKI 与 C797S。VRN110755（EGFR C797S）在 C797S 阳性亚组 ORR 87.5%、ctDNA C797S 清除率 83.3%；BH-30643（EGFR C797S，SOLARA）在 C797S 人群中 43% 达 RECIST 缓解、86% 肿瘤缩小，且无 MET/KRAS 共突变、未化疗者更优。C797S 这一 osimertinib（EGFR T790M）最常见的耐药机制，正成为下一代 EGFR-TKI 的攻坚重点。四、疗效之外：安全性管理成为胜负手双抗、ADC 这类「重武器」的 AE 管理越来越直接决定疗效能否兑现：telisotuzumab vedotin（c-MET，Teliso-V）的周围神经病变（PN）亚组提示 ≥2 级 PN 与更高累积剂量（31 vs 11 mg）和更长治疗（9 vs 2 个月）相关；ABBV-706（SEZ6）的间质性肺炎/ILD 发生率仅 4.2%、中位起病 96 天，多可恢复；ifinatamab deruxtecan（B7-H3）（I-DXd）的 ILD/肺炎 13.1%（≥3 级 4.4%），提示 B7-H3 类 ADC 需重点管理肺部毒性——把剂量-暴露关系与毒性谱做透，是从「能获批」走向「能长期用」的关键。五、关键数据速览（依据本届前瞻摘要）代表药物 / 方向关键数据看点 ivonescimab（PD-1×VEGF）三代TKI耐药后 mOS 16.8 vs 14.0 月，HR 0.76 EGFR耐药后首个OS获益双抗 RC148（PD-1×VEGF）鳞癌一线 ORR 90.0%；PD-L1阴性 93.3% 卡位PD-L1阴性人群 amivantamab（EGFR×c-MET）+ lazertinib（EGFR） AMIGO-1 18m-PFS 66.7%；mPFS 25.1 月双抗+TKI 挑战奥希替尼 Rilvegostomig（PD-1×TIGIT） PD-L1≥50% 确认ORR 61.8%；mPFS 16.7 月 PD-1×TIGIT 一线免疫 ALK202（EGFR×c-MET 双抗ADC） 3.2mg/kg 组 ORR 50%、DCR 100% 双抗+ADC 技术融合 sacituzumab tirumotecan（TROP2）高肿瘤负荷 mOS HR 0.49；ORR 61.7% 疗效亚组深挖 ABBV-706（SEZ6） R/R SCLC ORR 52%、mOS 11.3 月 SCLC 新靶点 ADC YL201（B7-H3 ADC）+ serplulimab（PD-1） ES-SCLC 一线 cORR 85.4%、mPFS 12.9 月小细胞肺癌一线组合 taletrectinib（ROS1） TKI初治 cORR 89.8%、mPFS 46.1 月 ROS1 全程管理 furmonertinib（EGFR）+ pemetrexed ORR 88%、CNS ORR 84% 脑转移颅内应答六、总结 ① 竞争格局：EGFR 敏感突变一线趋饱和，真正的「战场」在耐药后与围手术期。谁能带来 OS 获益（而非仅 PFS），谁才有资格进入标准治疗——ivonescimab（PD-1×VEGF）、amivantamab（EGFR×c-MET）+ lazertinib（EGFR）均瞄准这一点。 ② ADC 从「泛肿瘤靶点」走向「精准+双抗」，并向 SCLC/罕见病理类型渗透。 TROP2 渐显拥挤，DLL3、SEZ6、HER3、c-MET 等新靶点与双抗 ADC 将成为下一条差异化赛道。 ③ 「分子缓解」与「安全性深度」成为新的研究竞争力。 ctDNA 清除、毒性谱（ILD/PN/CRS）的精细管理，会越来越多地影响临床开发策略与同类竞争。 ④ 未满足需求仍在：脑转移颅内疗效、罕见驱动基因（ROS1/罕见 EGFR/KRAS 耐药）、以及小细胞肺癌的长期生存，仍是值得投入的方向。总体而言，WCLC 2026 传递的信号是：肺癌治疗正从「单药/单靶」走向「双抗 × ADC × 小分子的精准组合」，市场欢迎在特定人群、特定场景带来确定性生存获益与可控安全性的差异化资产。（说明：本文全部数据源自 WCLC 2026 大会前瞻摘要，仅作信息梳理与行业观察；数值以官方最终发布为准，不构成临床或投资建议。）

2026-08-26

·劲方医药GenFleet

GFH375 Advances into 1L NSCLC Phase II Study including Monotherapy and Combination Regimens with EGFR antibody or Chemotherapy

GenFleet Therapeutics (2595.HK) announced that GFH375 has entered a phase II study for first-line treatment of patients with advanced, KRAS G12D-mutant non-small cell lung cancer (NSCLC). The multicenter, open-label, randomized trial features three arms including GFH375 monotherapy and two combination regimens pairing GFH375 with the EGFR antibody (cetuximab) or with chemotherapy （pemetrexed）. The study will be conducted in dozens of clinical sites across China, with Guangdong Provincial People’s Hospital as the leading site. GFH375 (also known as VS-7375 outside of China) stands as the first KRAS G12D inhibitor that received Breakthrough Therapy Designation (BTD) in China for NSCLC and has also been granted with the U.S. FDA’s Fast Track designation (FTD) for locally advanced unresectable or metastatic KRAS G12D-mutant NSCLC. Current first-line standard of care for KRAS G12D-mutant patients follows the treatment paradigm for oncogene-negative NSCLC, yielding only modest survival benefits. Moreover, effective therapeutic options after frontline progression remain scarce. Multiple real-world studies show that patients with KRAS G12D mutations experience significantly poorer outcomes under first-line chemotherapy - with or without immunotherapy - compared to KRAS wild-type or non-KRAS G12D-mutant patients. GFH375 has already entered the world’s first registrational phase III study of an oral KRAS G12D inhibitor in patients with NSCLC, and GFH375 demonstrated best-in-class efficacy in NSCLC patients according to publicly available data of KRAS G12D inhibitor monotherapies. Notably, updated phase I/II GFH375 monotherapy data in NSCLC patients (abstract No. 2333) have been selected for an oral presentation at this year’s World Conference on Lung Cancer (WCLC) to be held in Seoul, and the presentation will take place in the section Beyond KRAS: Emerging Targets, Smart Therapies on Sept. 14. On the combination front, preclinical data presented at this year’s American Association for Cancer Research (AACR) Annual Meeting demonstrated that in KRAS G12D-mutant NSCLC models, the combination of GFH375 with cetuximab delivered markedly superior antitumor activity compared with either agent alone. Moreover, GFH375 advanced into a phase Ib/II trial last year evaluating combinations with chemotherapy or cetuximab across multiple solid tumors; early data indicated a favorable safety and tolerability profile with no obvious overlapping toxicities. The data from the GFH375/cetuximab combination treating RAS-mutant solid tumors have been granted the eligibility for full submission of a Late-Breaking Abstract (LBA) at the European Society for Medical Oncology (ESMO) Annual Meeting in 2026. Yu Wang, M.D., Ph.D. Chief Medical Officer of GenFleet “Driven by the monotherapy efficacy of GFH375 in NSCLC and the active progression of multiple combination studies, we are confident in moving GFH375-based lung cancer therapies from late-line to the first-line setting. Over the past two years, multiple clinical programs for GFH375 have advanced efficiently, with clinical data across various tumor types consecutively selected for LBAs or oral presentations at major international academic conferences. Meanwhile, we deeply recognize the urgent need of KRAS G12D-mutant patients for innovative targeted therapies and look forward to more of our innovative therapies reaching patients.” About GFH375/VS-7375 GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays. GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China. In the U.S., GenFleet’s partner Verastem Oncology is evaluating VS-7375 in TARGET-D 202, a registration-directed study in NSCLC.GenFleet received the Breakthrough Therapy Designations granted by China’s CDE in 2026 for GFH375 in pretreated KRAS G12D-mutant NSCLC and metastatic pancreatic cancer respectively; Verastem received the Fast Track Designations granted by U.S. FDA for VS-7375 treating KRAS G12D-mutant pancreatic ductal adenocarcinoma across all lines of therapy in 2025, and treating locally advanced unresectable or metastatic KRAS G12D-mutant NSCLC in 2026. About GenFleet Therapeutics With a focus on cutting-edge therapies, GenFleet Therapeutics is dedicated to serving significant unmet medical needs globally in oncology and immunology. Leveraging its deep understanding of disease biology and translational medicine, GenFleet has established a proprietary and fully integrated R&D system that yields a robust pipeline of multiple cutting-edge products with novel mechanisms and global IP.Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe. The company has set up a highly differentiated RAS-targeted matrix including selective and pan-RAS inhibitors of diverse molecular types, with most assets leading their categories in clinical progress in China or globally. In addition, the company has pioneered a series of first-in-class combination therapies based on dual-target synergistic mechanisms. By integrating clinical needs and insights, GenFleet is dedicated to expanding its portfolio into major therapeutic areas including pancreatic cancer, NSCLC, and cachexia. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world. Forward-looking Statements Specific information in this press release may contain or constitute forward-looking words that are not historical facts. They can be identified by using forward-looking terminology, such as "predict", "believe", "plan", "predict", "expect", "will", "may", "should" and other words of similar meanings.Based on the management's current beliefs, plans, estimates and expectations of the company's operation and market trends subject to changes beyond control, the forward-looking terminology reflects GenFleet Therapeutics' beliefs, plans, estimates and expectations of future development. Actual outcome in the future may differ significantly from forward-looking words owing to market, policy, and R&D uncertainties, among others.Subject to the above-mentioned uncertainties, GenFleet Therapeutics makes no expressed or implied guarantee as to the accuracy, completeness or feasibility of this presentation, and you are cautioned not to solely rely on such forward-looking words.Neither the company nor any of its directors, officers, employees, shareholders, agents, related parties, consultants or representatives will be liable to you or any other person for consequences resulting from using this presentation. Investors are advised to exercise due diligence with reference to the company's official disclosures for decision-making.

2026-08-25

·allsci.com

Ivonescimab Phase III PFS benefit gets peer-reviewed backing ahead of FDA decision

Peer-reviewed results from the global Phase III HARMONi trial have confirmed a significant PFS benefit for ivonescimab in EGFR-mutated NSCLC, but the study's primary overall survival (OS) analysis remained non-significant ahead of a US FDA decision due November 14, 2026. The primary analysis of the trial data was published in The Lancet Oncology, while Summit Therapeutics Inc.'s (Nasdaq: SMMT) press release plans to present updated OS data at the World Conference on Lung Cancer (WCLC 2026) on September 15, 2026. HARMONi is a randomized, double-blind, placebo-controlled Phase III trial enrolling patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease progressed after a third-generation EGFR tyrosine kinase inhibitor (TKI). The study ran across 114 centers in Asia, Europe, and North America. At the primary analysis, ivonescimab plus platinum-doublet chemotherapy produced a median progression-free survival (PFS) of 6.8 months versus 4.4 months with placebo plus chemotherapy, a hazard ratio of 0.52 (95% CI: 0.41–0.66; p<0.0001) assessed by independent radiographic review. The PFS benefit was consistent across preplanned subgroups. At the time of the primary OS analysis, the combination showed a positive OS trend that did not reach statistical significance. Treatment-related grade 3–5 hemorrhage events occurred in fewer than 1% of patients in the ivonescimab arm, consistent with prior clinical experience, Summit said. Ivonescimab simultaneously blocks PD-1 and vascular endothelial growth factor (VEGF) through a single tetravalent bispecific antibody engineered by China-based Akeso Inc. (HKEX: 9926.HK). The molecule is designed to preferentially accumulate in the tumor microenvironment, where both PD-1 and VEGF are more highly expressed than in normal tissue. Summit holds commercialization rights in North America, South America, Europe, the Middle East, Africa, and Japan; Akeso retains rights elsewhere, including China, where ivonescimab was first approved in May 2024 for EGFR-TKI-resistant non-squamous NSCLC. The post-third-generation TKI setting has historically resisted immunotherapy. Prior Phase III studies of PD-1 monoclonal antibodies failed to show PFS or OS benefit in this population, making HARMONi's statistically significant PFS result the first for an immunotherapy-based regimen in a global trial of this kind, Summit said. An updated OS analysis based on a June 2026 data cut showed a continued positive OS trend, with western patients achieving an OS hazard ratio of 0.76, consistent with the overall study population. That data will be presented at WCLC 2026. The HARMONi-A study — a single-region China-based predecessor trial in a similar population — demonstrated a statistically significant OS benefit (HR 0.74; p=0.019), providing supportive context for the global dataset. Summit proceeded with its BLA submission based on the PFS result and the positive OS trend, citing the absence of any FDA-approved regimen with demonstrated OS benefit in this patient population and the consistency of results between Asian and western cohorts. The PDUFA goal action date is November 14, 2026. In the US, Johnson & Johnson's EGFR/MET-targeted bispecific antibody Rybrevant (amivantamab-vmjw) is approved with carboplatin and pemetrexed for patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations whose disease has progressed on or after an EGFR TKI. That molecule's September 2024 approval was based on the Phase III MARIPOSA-2 trial, in which the regimen produced a median PFS of 6.3 months versus 4.2 months with chemotherapy alone (HR 0.48; 95% CI: 0.36–0.64). Ivonescimab combines PD-1 and VEGF blockade, potentially providing a mechanistically distinct treatment option if approved. Cross-trial comparisons between HARMONi and MARIPOSA-2 remain limited by differences in eligibility criteria, comparator arms, and study design. Summit's global Phase III program for ivonescimab now spans five company-sponsored studies, including HARMONi-3 (first-line NSCLC versus Merck's Keytruda (pembrolizumab) plus chemotherapy), HARMONi-7 (first-line high PD-L1 NSCLC monotherapy versus pembrolizumab), HARMONi-GI3 (first-line metastatic colorectal cancer), and HARMONi-GU1 (first-line urothelial carcinoma). Akeso separately received NMPA approval in August 2026 for ivonescimab plus chemotherapy in first-line squamous NSCLC based on HARMONi-6 OS data — the third approved indication for the molecule in China. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article

临床3期临床结果上市批准免疫疗法

100 项与培美曲塞二钾相关的药物交易

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适应症	国家/地区	公司	日期
ALK阳性非小细胞肺癌	美国	Avyxa Pharma LLC	2025-10-03
局部晚期非鳞状非小细胞肺癌	美国	Avyxa Pharma LLC	2024-06-28
恶性胸膜间皮瘤	美国	Avyxa Pharma LLC	2024-06-28
转移性非鳞状非小细胞肺癌	美国	Avyxa Pharma LLC	2024-06-28
非鳞状非小细胞肺癌	美国	Avyxa Pharma LLC	2024-06-28
复发性非鳞状非小细胞肺癌	美国	Avyxa Pharma LLC	2024-06-28

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适应症	最高研发状态	国家/地区	公司	日期
非小细胞肺癌 III期	临床3期	美国	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	美国	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	中国	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	阿根廷	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	澳大利亚	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	比利时	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	巴西	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	加拿大	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	法国	Eli Lilly & Co.	2008-09-01
非小细胞肺癌IIIB期	临床3期	德国	Eli Lilly & Co.	2008-09-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ChiCTR1800016615 (ASCO_Breakthrough2026)	临床2期	软脑膜转移性恶性肿瘤 ALK-mutant	25	Intrathecal pemetrexed (ALK-mutant non-small-cell lung cancer + leptomeningeal metastases)	壓艱獵衊繭顧鬱遞網衊(壓窪觸觸鬱構鑰鏇壓艱) = 鑰夢糧獵簾鹽觸簾餘繭願夢簾獵積觸壓壓膚鹽 (願淵醖夢簾鹽糧範餘糧, 13.0 ~ 23.6) 更多	积极	2026-06-25
ASCO_Breakthrough2026	N/A	EGFR突变肺癌 EGFR-mutated	119	Carboplatin+Pemetrexed+Bevacizumab	築衊遞鬱廠夢餘醖餘製(範壓繭顧繭鹹構繭網蓋) = Distinct safety profiles were identified: thrombocytopenia and hepatic dysfunction occurred more frequently with CPemB, whereas febrile neutropenia, rash, and peripheral neuropathy were more common with ABCP. 艱鹽廠鑰鹽觸獵鑰築觸 (淵遞淵構獵顧齋鬱簾壓 ) 更多	积极	2026-06-25
ASCO_Breakthrough2026	N/A	EGFR突变肺癌 EGFR-mutated	119	Atezolizumab+Bevacizumab+Carboplatin+Paclitaxel		积极	2026-06-25
NCT06663306 (ESMO_ELCC2026)	临床1期	软脑膜转移性恶性肿瘤 EGFR mutations	6	Intrathecal pemetrexed (IP)	顧襯願觸遞鏇艱築淵齋(蓋醖築繭鬱築淵構襯鑰) = the most common treatment-related adverse events being myelosuppression and elevated ALT/AST, mostly grade 1 簾鬱壓積夢鬱獵襯膚鹽 (願艱淵鹽鬱觸夢窪醖窪 )	积极	2026-03-25
NCT03559049 (CTgov)	临床1/2期	转移性非小细胞肺癌 \| 非鳞状非小细胞肺癌	25	Carboplatin+Pemetrexed+Rucaparib+Pembrolizumab	築鹽醖願顧鏇鏇顧醖範(繭鬱願築積餘獵窪窪鏇) = 夢餘構窪遞艱襯築積鹽衊選膚鏇艱網膚窪膚糧 (鬱選鹹鑰積廠顧鏇憲壓, 積壓糧鏇鹽顧齋構夢鏇 ~ 糧廠餘範獵選膚窪壓觸) 更多	-	2026-02-12
ChiCTR2100047017 (ESMO_ASIA2025)	临床2期	EGFR+	18	Aumolertinib + intrathecal pemetrexed	窪壓觸觸窪築壓繭觸鹹(選顧選鑰顧顧襯夢淵餘) = The most common adverse event was myelosuppression (n=5; 27.8%), which reversed after symptomatic treatment. 簾選艱鹹網衊醖襯壓衊 (製觸顧積廠築製築衊鹽 )	积极	2025-12-05
ESMO_ASIA2025	N/A	肾盂输尿管移行细胞癌转移 EGFR exon 20 insertion \| MTAP loss	1	Amivantamab+pemetrexed-based chemotherapy (EGFR exon 20 insertion + MTAP loss + Metastatic upper tract urothelial carcinoma)	夢願糧簾窪憲構鬱衊網(餘鏇鹹選襯網壓築觸築) = 獵構醖遞簾糧夢簾觸襯選遞範夢簾憲遞蓋廠鑰 (觸鏇繭艱襯憲選觸齋壓 )	积极	2025-12-05
NCT04211090 (CAP-BRAIN, Pubmed \| EClinicalMedicine)	临床2期	晚期非小细胞肺癌一线	45	Camrelizumab + Pemetrexed + Carboplatin	遞簾鏇觸遞餘夢觸繭壓(繭醖齋膚餘繭繭觸淵衊) = 遞構鬱廠鏇簾鬱廠齋鹹膚壓構鹹壓鬱積餘鏇糧 (蓋憲齋膚窪齋艱選廠鑰, 40.9 ~ 73.0) 更多	积极	2025-12-01
NCT03132532 (CTgov)	临床2期	复发性非小细胞肺癌 \| 不可切除的非小细胞肺癌	20	Quality-of-Life Assessment+Etoposide+Carboplatin+Pemetrexed+Paclitaxel+cisplatin (Arm A (Platinum Doublet Chemotherapy, Lower Dose PBT))	蓋願範鬱鏇齋製齋膚繭 = 糧簾製鏇淵壓顧淵淵憲糧觸顧憲選網鬱築鬱願 (遞齋廠網憲鬱鬱壓襯醖, 顧範簾衊鹽壓製壓製襯 ~ 製夢簾憲鑰製艱餘衊鏇) 更多	-	2025-11-25
NCT03132532 (CTgov)	临床2期	复发性非小细胞肺癌 \| 不可切除的非小细胞肺癌	20	Quality-of-Life Assessment+Carboplatin+Paclitaxel (Arm C (Platinum Doublet Chemotherapy, Higher Dose PBT))	蓋願範鬱鏇齋製齋膚繭 = 糧鑰衊鏇蓋鹽蓋窪繭齋糧觸顧憲選網鬱築鬱願 (遞齋廠網憲鬱鬱壓襯醖, 廠糧積鹽構鹽願遞醖製 ~ 壓醖醖蓋鬱鑰憲築衊鑰) 更多	-	2025-11-25
ESMO2025	N/A	EGFR突变的非小细胞肺癌二线 EGFR mutation	241	Osimertinib + Osimertinib/pemetrexed (EGFR common mutations + advanced NSCLC)	觸範獵衊製淵襯鏇製網(繭繭選構醖鑰繭艱積範) = 簾廠遞壓醖獵選壓鏇艱願遞積膚簾築艱淵餘網 (顧築齋餘選觸鬱壓選齋, 8.1 ~ 11.1) 更多	不佳	2025-10-17
ESMO2025	N/A	软脑膜转移性恶性肿瘤	150	NGS-guided double dose of targeted therapy combined with intrathecal pemetrexed chemotherapy	遞願襯築鹽簾壓顧鏇壓(餘廠築築蓋齋積繭餘構) = The most common AEs were myelosuppression (48.0%) and elevation of hepatic aminotransferases (25.3%). 鑰襯顧蓋製積積淵醖鹹 (餘壓壓範觸餘鏇淵夢夢 )	积极	2025-10-17