获批铂化疗后进展的EGFR exi20ns NSCLC，基
FDA granted accelerated approval to amivantamab-vmjw (Rybrevant, Janssen) for locally advanced/metastatic NSCLC w/EGFR exon 20 insertion mutations that progressed after platinum-based chemotherapy.
Approval was based on CHRYSALIS, a multicenter, non-randomized, open label, multicohort clinical trial (NCT02609776) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Efficacy was evaluated in 81 patients with advanced NSCLC with EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. Patients received amivantamab-vmjw once weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review (BICR) and response duration. The ORR was 40% (95% CI: 29%, 51%) with a median response duration of 11.1 months (95% CI: 6.9, not evaluable).
The most common adverse reactions (≥ 20%) were rash, infusion-related reactions, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting.
The recommended dose of amivantamab-vmjw is 1050 mg for patients with baseline body weight < 80 kg, and 1400 mg for those with body weight ≥ 80 kg, administered weekly for 4 weeks, then every 2 weeks thereafter until disease progression or unacceptable toxicity.
JNJ-372用于含铂化疗后的EGFRex20ins NSCLC
安全性方面：≥Gr3 TRAE16%，TRAE引起的治疗终止只有4%
不良事件方面，2%的治疗终止是因为皮疹这个EGFR相关的毒性，虽然12%的患者报道腹泻其中10%治疗相关但基本是1-2级，66%的患者报道任意级别的输液反应≥Gr3的只有3%，而且巨大部分发生在首次输液时基本不影响后续治疗
疗效方面：ORR 40%，CBR 74%，DoR 11.1mo，而且几乎所有亚组的缓解率都很接近
PFS 8.3mo，OS 22.8mo
相当不错的结果
另外相比ASCO20上的结果：ORR和CBR差不大，但DoR只有7mo，这次我们看到了很多深度的缓解，DoR也长达11.1mo
比较下
amivantamab vs mobocertinib（JNJ372 vs TAK778） 用于铂化疗后进展的ex20ins NSCLC
样本量：80 vs 114
ORR ：40% [29-51] (IRC) vs 35% [26-45] (inv) & 28% [20-37] (IRC)
DOR：11.1mo [6.9-NR] vs 17.5mo [7.4-20.3]
PFS：8.3mo [6.5-10.9] vs 7.3 [5.5-10.2]
剩下就是Amivantamab联合Lazertinib
ASCO19初次报道了单药在经治的EGFRm NSCLC中的疗效 ORR 30%左右，虽然MET扩增是常见的EGFR TKI后的耐药机制，但是化疗在二线EGFRm患者疗效也是差不多30%，实在是体现不出一个靶向药的优势
ESMO20报道了JNJ-372联合三代EGFR TKI lazertinib治疗晚期EGFRm的NSCLC
lazertinib在T790M中ORR 66%，DCR 93%
联合的Ph1，剂量递增阶段Lazertinib固定240mg QD，JNJ-372从700/1050mg爬到1050/1400mg，后者确定为RP2D，扩展到对Osi耐药但未经化疗治疗和未经治疗2个Cohort
患者基线只有剂量扩张阶段的treatment naive Cohort的患者先前未经治疗，其中59%的患者先前接受过1/2 代TKI，59%的患者先前接受过3代 TKI
安全基本都是Gr 1-2
Osi经治但未化疗患者 ORR 36%和ASCO19的接近，没有披露DoR 应该会比化疗长，缓解的患者基本都是2线接受Osi的，这个时候起作用的只是JNJ-372了
游泳图显示 88%的缓解患者仍持续缓解中
这部分就是双药一线了，20例患者全部PR，应该还是样本问题吧，另外Osi单药一线也有ORR 80% DCR 97%，EGFR敏感突变看ORR意义已经不大了
Osi的bar太高，一线2个加起来能高出多少，祝福光头强吧
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