獲批鉑化療后進展的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用于含鉑化療后的EGFRex20ins NSCLC
安全性方面：≥Gr3 TRAE16%，TRAE引起的治療終止只有4%
不良事件方面，2%的治療終止是因為皮疹這個EGFR相關的毒性，雖然12%的患者報道腹瀉其中10%治療相關但基本是1-2級，66%的患者報道任意級別的輸液反應≥Gr3的只有3%，而且巨大部分發(fā)生在首次輸液時基本不影響后續(xù)治療
療效方面：ORR 40%，CBR 74%，DoR 11.1mo，而且?guī)缀跛衼喗M的緩解率都很接近
PFS 8.3mo，OS 22.8mo
相當不錯的結(jié)果
另外相比ASCO20上的結(jié)果：ORR和CBR差不大，但DoR只有7mo，這次我們看到了很多深度的緩解，DoR也長達11.1mo
比較下
amivantamab vs mobocertinib（JNJ372 vs TAK778） 用于鉑化療后進展的ex20ins NSCLC
樣本量：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聯(lián)合Lazertinib
ASCO19初次報道了單藥在經(jīng)治的EGFRm NSCLC中的療效 ORR 30%左右，雖然MET擴增是常見的EGFR TKI后的耐藥機制，但是化療在二線EGFRm患者療效也是差不多30%，實在是體現(xiàn)不出一個靶向藥的優(yōu)勢
ESMO20報道了JNJ-372聯(lián)合三代EGFR TKI lazertinib治療晚期EGFRm的NSCLC
lazertinib在T790M中ORR 66%，DCR 93%
聯(lián)合的Ph1，劑量遞增階段Lazertinib固定240mg QD，JNJ-372從700/1050mg爬到1050/1400mg，后者確定為RP2D，擴展到對Osi耐藥但未經(jīng)化療治療和未經(jīng)治療2個Cohort
患者基線只有劑量擴張階段的treatment naive Cohort的患者先前未經(jīng)治療，其中59%的患者先前接受過1/2 代TKI，59%的患者先前接受過3代 TKI
安全基本都是Gr 1-2
Osi經(jīng)治但未化療患者 ORR 36%和ASCO19的接近，沒有披露DoR 應該會比化療長，緩解的患者基本都是2線接受Osi的，這個時候起作用的只是JNJ-372了
游泳圖顯示 88%的緩解患者仍持續(xù)緩解中
這部分就是雙藥一線了，20例患者全部PR，應該還是樣本問題吧，另外Osi單藥一線也有ORR 80% DCR 97%，EGFR敏感突變看ORR意義已經(jīng)不大了
Osi的bar太高，一線2個加起來能高出多少，祝福光頭強吧
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