Polatuzumab Vedotin-Piiq

If approved, Lunsumio and Polivy could offer an off-the-shelf, chemo-free regimen for patients with second-line large B-cell lymphoma. Roche has demonstrated the power of combining two of oncology’s hottest modalities—bispecifics and antibody-drug conjugates (ADCs)—in a Lunsumio-Polivy regimen in large B-cell lymphoma (LBCL).The combination of the CD20xCD3 bispecific Lunsumio and the CD79b-directed ADC Polivy significantly reduced the risk of progression or death by 59% versus the traditional R-GemOx regimen in patients with previously treated LBCL who are not eligible for stem cell transplant. R-GemOx includes Roche’s own Rituxan and the chemotherapies gemcitabine and oxaliplatin.Patients in the Lunsumio-Polivy group went a median 11.5 months without disease progression versus 3.8 months for R-GemOx, according to the primary analysis of the phase 3 Sunmo study presented at the International Conference on Malignant Lymphoma.Roche said it will submit the trial results to global health authorities, including the FDA. While Lunsumio is currently approved as an intravenous infusion to treat follicular lymphoma, the Sunmo trial uses a subcutaneous formulation of the drug. Polivy, meanwhile, received the FDA’s approval as part of a combination for certain previously untreated patients with LBCL in 2023.The positive Sunmo readout could give Roche another shot at second-line LBCL after the regulatory prospects of its other CD20xCD3 bispecific, Columvi, were thrown into doubt in the U.S.In its own phase 3 study, Columvi, used in tandem with GemOx, led to a 63% reduction in the risk of disease worsening or death in patients with previously treated diffuse large B-cell lymphoma (DLBCL). The median progression-free survival was 12.1 months for Columvi-GemOx and 3.3 months for control. The Columvi regimen also significantly reduced the risk of death by 41% compared with R-GemOx at the primary analysis of the Starglo trial.Despite the positive readout, an FDA advisory committee agreed with an FDA internal analysis that the Starglo results are not applicable to a U.S. patient population. The Starglo study enrolled 48% of its total population in Asia but just 9% of patients in the U.S. In addition, an FDA subgroup analysis found a negative patient survival trend in participants from non-Asian countries.Given the bleak feedback, the Starglo regimen looks unlikely to be approved in the U.S., even though the European Commission has cleared it in second-line DLBCL. Overall survival data remained immature in the Sunmo trial of the Lunsumio-Polivy regimen. That metric currently numerically favored Lunsumio-Polivy, with a preliminary 20% death risk reduction. But there’s no breakdown of survival data by subgroups. The study is continuing toward its final overall survival analysis. A statistically significant overall survival showing is not required to win an approval in second-line LBCL in the U.S. The FDA has previously approved CAR-T therapies from Gilead Sciences and Bristol Myers Squibb in the disease setting based on the event-free survival endpoint.However, regional representation might become a sticking point for Roche with the FDA again. Sunmo enrolled 20—or about 10%—of its 208 patients in the U.S. and Canada. Latin America represents 41% of the study participation and East Asia 38%.But in a piece of good news for Roche, the progression-free survival analysis for the small North America cohort showed a massive 87% benefit in favor of Lunsumio-Polivy.Unlike Starglo, Sunmo also enrolled patients with high-grade B-cell lymphoma and follicular lymphoma grade 3b in addition to the 78% of individuals with DLBCL. Disease progression data favored Lunsumio-Polivy in each of the three subgroups, with DLBCL’s 62% the biggest among the three lymphoma types.The treatment effect looked similar for patients who received just one prior line of therapy versus at least two.In terms of toxicity, the rates of treatment-related grade 3 or 4 adverse events were similar, at 52.6% and 51.6%, for Lunsumio-Polivy and R-GemOx, respectively. And treatment-related deaths were recorded in 1.5% and 3.1% of patients in the groups, respectively.“If approved, this off-the-shelf treatment combination of [Lunsumio] and [Polivy] could be administered over a fixed period of time, without mandatory hospitalization or traditional chemotherapy, which could provide a meaningful option for patients with relapsed or refractory LBCL,” the Sunmo study’s lead author, Jason Westin, M.D., from the MD Anderson Cancer Center, said in a statement Friday. Between its two CD20xCD3 T-cell engagers, Roche angled Columvi toward the more aggressive DLBCL in its development plan. The Swiss pharma is also running the phase 3 Skyglo study, testing the combination of Columvi, Polivy and the R-CHP regimen in first-line DLBCL.Meanwhile, AbbVie and Genmab are running the phase 3 Epcore NHL-2 trial for its rival CD20xCD3 bispecific Epkinly in a combination with R-CHOP in newly diagnosed DLBCL. 

临床试验病友交流群（点击）一、新药快讯1、晚期小细胞肺癌有望迎来ZL-1310的新药，疾病控制率高达93%ZL-1310属于一款抗体偶联药，该药目前的针对肿瘤类型是小细胞肺癌，在最近的一期临床试验中，对于携带DLL3突变、此前接受过1种或多种治疗的74名晚期小细胞肺癌患者，使用ZL-1310治疗让37%的患者肿瘤大幅度缩小，而疾病控制率则达到了93%。尽管该药还处在早期临床试验阶段，距离获批上市还有时间，但是仍然值得非常关注。2、同时靶向HER2两个位置，泽尼达妥单抗联合化疗治疗胃食管腺癌胃食管腺癌是一组包含胃、食管和胃食管交界处腺癌的恶性肿瘤，很多患者晚期才被确诊，20%的患者存在HER2表达阳性，泽尼达妥单抗是一种新型双特异性抗体，可以同时靶向HER2的两个非重叠结构域，同时还能激活免疫介导效应。最近一项二期临床试验表明，泽尼达妥单抗联合标准化疗一线治疗胃食管腺癌，确认的治疗应答率达到了76.2%，中位无进展生存时间达到了12.5个月，中位总生存时间为36.5个月，疾病控制率达到了88.1%。3、靶向双特异性抗体药联合ADC药物治疗淋巴瘤，无进展生存期延长3倍最近，根据一项三期临床试验SUNMO结果，CD20和CD30的双特异性靶向抗体药物Lunsumio，联合CD79b的抗体偶联药Polivy，在治疗无法进行造血干细胞移植的复发或难治性大B细胞淋巴瘤患者中，相比利妥昔单抗联合奥沙利铂方案，中位无进展生存时间延长了3倍。客观缓解率也获得了明显提升，预计很快向FDA发起上市申请。二、抗癌前沿1、2025年世界肺癌大会报道中国肺癌软脑膜转移治疗成果2025年第25届世界肺癌大会将在9月在西班牙召开，南京鼓楼医院老年肿瘤科的肺癌脑膜转移研究将会报道，133名接受鞘注培美曲塞化疗的肺癌脑膜转移患者，中位总生存时间达到了14.2个月，生存时间超过6个月的比例是83.5%，生存时间超过1年的比例是56.6%，91.7%的患者鞘注培美化疗后临床症状得到了改善，64.3%的患者影像学稳定或缓解。EGFR常见突变的生存期显著长于罕见突变患者，分别是15.9个月和11.7个月。