Janaayo 26, 2025, Xarunta Qiimaynta Daawada (CDE) ee Maamulka Badeecadaha Caafimaadka Qaranka ee Shiinaha ayaa ku dhawaaqday in duritaanka LM-108 loogu talagalay in lagu daro daaweynta degdegga ah ee burooyinka adag ee horumarsan ee leh xasillooni darro microsatellite ah (MSI-H) ama cilladaha hagaajinta aan isku midka ahayn (dMMR) ee horumaray ka dib markii lagu daaweeyay daawooyinka ka hortagga difaaca jirka (ICI).
LM-108 waa unug difaac oo cusub oo Fc-optimized ah, oo ka hortagga CCR8 monoclonal ah kaas oo si gaar ah u baabi'iya Tregs-ka burooyinka ku soo qulqulaya.
Ku saabsan CCR8:
CCR8 (chemokine receptor 8) waa xubin ka tirsan qoyska receptor-ka chemokine ee hoos yimaada qoyska receptor-ka borotiinka isku xiran (GPCR). Daraasado hore ayaa shaaca ka qaaday in muujinta CCR8 ay ku yar tahay unugyada dhiigga ee durugsan iyo unugyada caadiga ah, laakiin si gaar ah ayaa loogu hagaajiyay Tregs-ka burooyinka ku faafa ee kansarrada badan oo ay ku jiraan kansarka naasaha, kansarka mindhicirka, iyo kansarka sambabada. Unugyada difaaca jirka ee Anit-CCR8 waxay si xushmad leh u dhexdhexaadin karaan dhimista Tregs-ka burooyinka ku faafa, taasoo kor u qaadaysa jawaabta difaaca jirka ee ka hortagga burooyinka iyo joojinta koritaanka burooyinka.
AShirka Sanadlaha ah ee ASCO 2024，soo sheeg falanqayn isku dhafan oo natiijooyinka laga soo qaatay daraasado 3 marxaladood 1/2 ah (NCT05199753; NCT05255484; NCT05518045) si loo qiimeeyo waxtarka iyo badbaadada LM-108 iyadoo lala kaashanayo daaweynta ka hortagga PD-1 ee bukaanada qaba kansarka caloosha.
Hababka: Bukaannada u qalma ee qaba kansarka caloosha oo lagu daweeyay LM-108 oo lagu daray antibody-ga ka hortagga PD-1 ayaa lagu daray falanqaynta. Bukaannada waxaa la siiyay LM-108 xididka ah heerarka qiyaasta ee 3 mg/kg Q2W, 6 mg/kg Q3W, ama 10 mg/kg Q3W oo lagu daray antibody-ka ka hortagga PD-1 (pembrolizumab 200 mg Q3W ama 400 mg Q6W ama toripalimab 240 mg Q3W). Dhammaadka ugu horreeya wuxuu ahaa ORR oo lagu qiimeeyay baarayaasha halkii RECIST v1.1. Dhammaadka labaad waxaa ka mid ahaa badbaadada, natiijooyinka kale ee waxtarka, iyo falanqaynta biomarkers. Taariikhda goynta xogta ee falanqaynta la isku daray waxay ahayd Diseembar 25, 2023.
Natiijooyinka: Afartan iyo siddeed bukaan oo qaba kansarka caloosha (da'da dhexe: 60.5 sano; ragga: 72.9%) oo ka yimid Shiinaha, Mareykanka, iyo Australia ayaa lagu daweeyay ≥ 1 qiyaas oo LM-108 ah iyadoo lagu daray pembrolizumab ama toripalimab. Inta badan (n = 47, 97.9%) bukaanada waxay heleen ugu yaraan 1 daaweyn ka hortagta kansarka ka hor, 43 (89.6%) waxay heleen daaweyn ka hortagta PD-1 ka hor. Dhacdooyinka xun ee la xiriira daaweynta (TRAEs) waxay ka dhaceen 39 bukaan (81.3%), kuwaas oo dhacdooyinka ugu badan (≥15%) ay ahaayeen alanine transaminase oo kordhay (25.0%), aspartate transaminase oo kordhay (22.9%), unugyada dhiigga cad oo yaraaday (22.9%), dhiig yari (16.7%). Darajada ≥ 3 TRAEs waxay ka dhacday 18 bukaan (37.5%), dhacdooyinka ugu badan (≥ 4%) waxay ahaayeen dhiig-yaraan (8.3%), lipase-ka oo kordhay (4.2%), finan (4.2%), iyo tirada lymphocytes-ka oo hoos u dhacday (4.2%). 36 bukaan oo lagu qiimeeyay waxtarka dhammaan daawooyinka, ORR waxay ahayd 36.1% (95% CI 20.8%–53.8%) iyo DCR waxay ahayd 72.2% (95% CI 54.8%–85.8%). Celceliska PFS wuxuu ahaa 6.53 bilood (95% CI 2.96–NA). 11 bukaan oo cudurkoodu uu ku soo baxay daaweynta safka hore, ORR wuxuu ahaa 63.6% (95% CI 30.8%–89.1%) iyo DCR wuxuu ahaa 81.8% (95% CI 48.2%–97.7%). 11-kii bukaan ee u gudbay daaweynta safka hore, 8 ka mid ah waxay lahaayeen muujinta CCR8 oo sareysa. 8-dan bukaan, ORR waxay ahayd 87.5% halka DCR-na ay ahayd 100%, iyadoo la arkay 1 CR, 6 PR, iyo 1 SD.
Gunaanad: LM-108 oo ay weheliso antibody-ga ka hortagga PD-1 ayaa muujiyay firfircooni ka-hortagga burooyinka oo rajo leh oo loogu talagalay bukaanada qaba kansarka caloosha oo iska caabbiyay daaweynta ka hortagga PD-1. Daaweynta isku-dhafka ah si fiican ayaa loo dulqaatay. Natiijooyinkani waxay taageerayaan qiimeyn dheeraad ah oo lagu sameeyo LM-108 ee kansarka caloosha ee CCR8 ee togan.
Waqtigan xaadirka ah, waxaa weli jira tijaabooyin caafimaad oo badan oo ku saabsan teknoolojiyada cusub ee ka hortagga kansarka ee Shiinaha oo raadinaya bukaanno. La-tashi ku saabsan daawooyinka cusub iyo teknoolojiyada, waxaad la xiriiri kartaa Waaxda Caalamiga ah ee Isbitaalka Oncology ee Gobolka Koonfureed ee Beijing.
Lambarka Taleefanka: 4008803716
Email：myimmnet@163.com
Tixraacyada
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2.https://www.lanovamedicines.com/en
3.https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2504
Waqtiga boostada: Febraayo-06-2025