美国制药与生物技术：ASCO现场医师洞察

Us Pharma & Biotech: Insights from a physician on the ground atASCO cancer clinicianandresearcher.The sessioncovered themost important datapresentedover the weekend, with Dr. Hirsch offering his clinical perspective on a range of emergingtreatments and trial readouts across early- and late-stage NSCLC. +19173448407courtney.breen@bernsteinsg.com +19173448613 disease,theHARMONi-6ivonescimabreadoutinsquamousNSCLC,updatedCROWNdataforlorlatinib,next-generation ALK and KRAS inhibitors, TROP2-directed ADCs, and broaderthemes around molecular testing, treatment duration, and the evolving chronic diseaseframing ofcertain lung cancersubtypes. +1 917 344 8314woody.polglasebernsteinsg.com +1917 344 8324yi.zhao@bernsteinsg.com ·HARMONi-6was encouraging,butthecriticalopenquestioniswhethera China-only studytranslates toa global population.The OS HR of O.66with manageableVEGF-related bleeding risk in squamous NSCLC was better than feared, but Dr.Hirschcautioned that patient selection details were descriptive-only,age was capped at 75,that he wouldnot anchor prescribing to a hazard ratio-approval plus a consistentHARMONi-3 readout in a global population are the two conditions needed forthe drugto earn a place in the clinic; 0S data from H3 are expected in H22026. +19173448495louisa.qiu@bernsteinsg.com Specialist Sales Christian Moore+19173448555christian.moore@bernsteinsg.com . RET adjuvant data sets a new benchmark in early-stage targeted therapy.LIBRETTO-432 delivered an HR of 0.17 for selpercatinib (LLY) in RET+ adjuvantNSCLC - among the most striking efficacy signals seen in this setting -though the keyimplementation challenge is detection,given~70% of RET+patients are never-smokersoutside standard screening criteria. Lorlatinib's bar remains extremely high, but Nuvalent has a crediblepath inlorlatinib-ineligible and lorlatinib-resistant patients. Median PFS is still not reachedat 7-year follow-up in CROWN - duration of therapy likely to be impressive; Nuvalent's4th-generationALKinhibitorshows~26%responseratesinlorla-relapsedpatientsandaddresses areal unmet need in those with neurological toxicity or comorbidities. KRASis thenextmajorbattleground infirst-lineNSCLC.Divarasib data inKRASG12C first-line were describedas potentially practice-changing,and the broader RASspace -including G12D and pan-RAS(ON) inhibitors from Revolution Medicines -ismovingfasterthanmanyanticipated. ·Sac-TMTis emerging as the most convincingTROP2 agent in NSCLC, but the allcomersvs.biomarker debateisunresolved.Dr.Hirsch foundthe data compellingbutremainsphilosophicallyconflictedaroundtheabsenceofacompanionbiomarkerDatroway. INVESTMENTIMPLICATIONS US Biopharma: We rate LLY and GILD Outperform; ABBV,AMGN, BMY, MRK, MRNA, PFE as Market-Perform. US Biotech: We rate NUVL and NBIX Outperform; BNTX, RVMD, JAZZ and INCY as Market-Perform; SMMT as Underperform The LIBRETTO-432 study in RET-positive patientsmoving into early-stage disease was highlightedas one of the most compelling data sets of the weekend, continuing a pattern set first by ADAURA in EGFR-mutant disease and ALINA in ALK-positive disease. Selpercatinib,a selective RET inhibitor with good CNS penetration, delivered a striking HR of O.17 in arandomized adjuvant setting,with event-free survival curves already well-separated despite the EFS endpoint not yetbeingreached-viewed clinically as a clearpositive.Notably,overall survival remains the endpoint patients care aboutmost, andnoquestions remain: the right duration of treatment (currently up to 3 years, with ctDNA monitoring a potential future tool, thoughearly-stage patients shed less circulating DNA than advanced patients, making detection less straightforward); the absenceof CNSprotectiondata; andcritically,howtodetectthesepatientsgiventhat~7o%ofRET+patientsarenever-smokers whoHirsch noted this figure may skew high given his NYC practice).Molecular characterization also remains incomplete in practice-tissue requirements are still a barrier evenin well-resourcedsettings, and liquidbiopsyin early-stage disease is less reliablethan in advanced disease. Several other studies in early-stage molecular subsets (including ROS and HER2-abnormal tumors)areunderway. A ChineseRET inhibitor also presented strong data with good brain penetrance, likely sufficient to support approval in China However,per standardFDApractice,replication in a global Western population will berequired before any US regulatorypathway can bepursued. HARMONi-6-Ivonescimab inSquamousNSCLCAkeso's (covered by Rebecca Liang) China-only HARMONi-6 evaluated ivonescimab (a PD-1xVEGFbispecific) plus chemotherapyversus tislelizumabplus chemotherapy in squamousNSCLC,delivering anOSHR of O.66with resultsindependent of PDL1status and manageabletoxicity.The bleeding risk historically associated withVEGFinhibition in squamoustumors (given their central, cavitating anatomy) was notably nota significantissue in H6,thoughquestions wereraised aroundpotential patient sele