Adavosertib

Lantern Pharma on Tuesday launched a new AI-powered module developed to assess how combination cancer treatments involving DNA-damaging agents (DDAs) and DNA damage response inhibitors (DDRis) work – and how effectively they fight tumours. The module is integrated into RADR, Lantern's proprietary drug discovery platform that leverages data analytics, experimental biology and machine learning to interpret complex biological data.The new model brings together genomic, transcriptomic and clinical data to predict pharmacodynamic synergy, enhance treatment efficacy and identify patient subgroups most likely to benefit from specific DDA-DDRi combinations. It has already informed the design of Lantern's FDA-cleared Phase Ib/II clinical trial of LP-184 in patients with biomarker-defined, treatment-resistant non-small-cell lung cancer."This AI-powered module is a transformative step in our mission to deliver personalised cancer treatments," said Panna Sharma, CEO and president at Lantern. By applying RADR to analyse multi-omics and clinical trial data, Sharma says Lantern aims to "reduce combination therapy development timelines and costs by one-third compared to traditional methods."A recent paper in Frontiers in Oncology describes how researchers developed the module by analysing data from 221 clinical trials involving DDA-DDRi combinations, encompassing 22 DDAs and 46 DDRis. The agents were categorised into eight DDA and 14 DDRi subclasses based on their mechanisms of action and molecular targets. Of these trials, 89 with interpretable outcomes were assigned scores reflecting clinical effectiveness, safety and overall benefit across tumour types and patient populations.According to the findings, non-PARP DDRi combinations demonstrated high positive outcome rates in interstrand cross-linker trials — particularly combinations involving Wee1 inhibitors like adavosertib with platinum agents or gemcitabine. For example, adavosertib plus carboplatin achieved a 43% overall response rate in patients with platinum-resistant or refractory epithelial ovarian cancer. Biomarkers such as TP53 mutations and homologous recombination deficiency signatures were highly predictive of response. Drug formulation improvements also appeared to reduce toxicity; liposomal doxorubicin, for instance, lowered cardiotoxicity, thereby broadening its therapeutic use in regimens with cumulative cardiac risks.With its multi-agentic architecture, the module not only classifies drugs and predicts combination efficacy, but also identifies biomarkers and optimises treatment strategies. Its adaptive framework allows it to continuously add new data, enabling Lantern to refine drug development in real time and accelerate clinical trial progress.Lantern is currently exploring licensing and commercialisation opportunities to broaden the reach and impact of its AI-powered technology.

点击蓝字 关注我们根据发表在《临床肿瘤学杂志》上的IIb期ADAGIO试验（NCT04590248）的数据，WEE1抑制剂Adavosertib（AZD1775）在接受过大量治疗的晚期复发性/持续性子宫浆液性癌患者中显示出初步的抗肿瘤活性，尽管该药物以300mg每日一次给药时耐受性不佳。[1]ADAGIO研究的入选患者符合以下条件：纯子宫浆液性癌或混合性子宫内膜癌（浆液性成分占肿瘤的≥10%）；根据RECIST 1.1标准有可测量病灶的证据；器官功能良好且骨髓功能正常；有证据表明既往接受过至少1种铂类化疗方案；ECOG体能状态评分为0或1分。这项开放标签、单组、多中心研究评估了Adavosertib单药治疗，起始剂量为300 mg，每日一次，第1-5天和第8-12天给药，21天为一个周期，直至患者出现病情进展或出现不可接受的毒性反应。主要终点是客观缓解率（ORR），根据RECIST 1.1标准通过盲法独立中心审查（BICR）确定；次要终点包括缓解持续时间（DOR）、缓解深度、无进展生存期（PFS）、总生存期（OS）、疾病控制率和安全性。研究结果显示，在全分析集的患者中，根据BICR评估疗效的患者（n=104）的ORR为26.0%（95%CI: 17.9%-35.5%），其中1.0%的患者达到完全缓解（CR），25.0%的患者达到部分缓解（PR）。经研究者评估可评价疗效患者（n=109）的ORR为21.1%（95%CI: 13.9%-30.0%），其中CR和PR率分别为1.8%和19.3%。对于已确认缓解的患者，BICR 评估的中位DOR为4.7个月，研究者评估的中位DOR为5.6个月；BICR评估的中位PFS为2.8个月；研究者评估的中位PFS为3.5个月。值得注意的是，97.2%的患者在起始剂量300 mg时出现了治疗相关不良反应（TRAE）。≥3级TRAE发生率达60.6%，其中最常见的≥3级TRAE是中性粒细胞减少症（21.1%）和疲劳（13.8%）。45.9%的患者出现了严重不良事件，26.6%的患者被认为与治疗相关。总计43.1%的患者死亡；3.7%的患者死于不良事件，包括脓毒症（2例）、心脏疾病（1例）和呼吸衰竭（1例）。值得注意的是，60.6%的患者需要减少剂量，76.1%的患者需要中断给药，17.4%的患者因不良事件停用Adavosertib。研究作者在论文中写道：“300 mg每日一次间歇性用药方案对Adavosertib的耐受性不佳，并观察到严重的中性粒细胞减少症和脓毒症等不良反应。然而，ADAGIO的经验表明，尽管Adavosertib的治疗窗口较窄，但探索WEE1抑制作为子宫浆液性癌潜在治疗靶点的科学原理仍然值得关注。”参考文献1.Liu JF, Colombo N, Oza AM, et al. ADAGIO: a phase IIb, open-label, single-arm, multicenter study assessing the efficacy and safety of adavosertib (AZD1775) as treatment for recurrent or persistent uterine serous carcinoma. J Clin Oncol. Published online April 22, 2025. doi:10.1200/JCO-24-01606（来源：《肿瘤瞭望》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。