Misty Dawn Shields

Today, the Phase 3 results of DeLLphi-305 (@AmgenOncology @AstraZeneca) were presented by @sands_jacob at #ESMO26. DeLLphi-305 delivered an unprecedented OS improvement (21.1 vs 12.7 mo, HR 0.42) for patients receiving tarlatamab + durvalumab, compared to durvalumab alone, in 1L maintenance after chemoIO induction for ES-SCLC. Studies like these provide renewed hope. However, this data brings forth multiple concerns regarding international access to care, interpretation of contribution of parts, patient selection, and sequencing. 1️⃣ Equitable access to cross-over: at time of POD, only 12.2% of ITT population in the durvalumab arm (34/278) and 18.9% (34/179) of those who received subsequent anti-cancer therapies had access to tarlatamab. This speaks to the global need to expand access to this life-saving therapy, as DeLLphi-301 demonstrated this impact with accessibility promptly available here in the USA as early as May 2024. Yet, @SclcSMASHERS all over the world still do not have this option even at relapse. 2️⃣ Line of therapy: while attrition to 2L may be significant in some practices & highlights the need to maximize proactive support & early palliative care, is there clear evidence of synergy with ICI+DLL3 TCE to transform outcomes, or is the effect additive? Preclinical data suggested synergy with this combination approach. However, within subgroup analyses of those receiving tarlatamab in subsequent treatment, particularly in the USA, it appears there is signal of additivity, given the nullification of OS benefit with DLL3 TCE cross-over (in those receiving it as 2nd LOT). Outside of risk of attrition, what variables favor using tarlatamab in 1LM vs 2L? Is the NE biology still preserved? Is the function of the immune system equivalently preserved following <4 weeks post chemoIO with myelosuppression? 3️⃣ Patient selection: Stratification with effective predictive biomarkers are key to know who can avoid any intensification, as they may be a durable ICI responder to monotherapy ICI. Who can we avoid tarlatamab every 2 weeks indefinitely? Who should receive lurbi + atezo? Or durva + tarla? More translational SCLC based biomarkers, beyond DLL3, are clearly of high unmet need to guide strategies. 4️⃣ Sequencing: if we use tarlatamab+durvalumab in the 1LM, what’s next? At POD, what approved option remains? Lurbi remains approved in the 1LM, but not at relapse. I-DXd BLA was voluntarily withdrawn. Trials are key, but enrollment for most global studies is brisk, particularly in the USA where enrollment is ~20% or less of the total cohort. @SclcSMASHERS @LUNGevity @IASLC @ASCO @NCCN @LungCancerEu @lcrf_org @OncBrothers @OncoAlert @oncodaily @OncLive @lungoncdoc @RManochakian @LauraAlderMD @LaurenByersMD @Annechiangmd

Thank you Dr. Anne Chiang @Annechiangmd @YaleCancer here at @IASLC #WCLC26 for highlighting our recent biomarker research on durable responders of lurbinectedin that identified ISL1 dependency as a novel neuroendocrine subtype in SCLC that predicts response, published in @MCT_AACR. Given the following growing evidence: 1) the press release with positive OS outcomes with DeLLphi-305 in the 1LM 2) negative confirmatory study with LAGOON (although multiple study design concerns existed, including pts with hx of tx brain mets) 3) sponsor withdrawal of lurbinectedin in the relapsed/refractory setting of ES-SCLC 4) risk for relapsed SCLC treatment gap while awaiting ADC approvals that are limited by ILD, myelosuppression, GI toxicity and acquired resistance development. … the prospective need to apply proposed biomarkers like ISL1 is important to understand who ultimately will benefit from lurbinectedin in their treatment of SCLC. @SclcSMASHERS @LUNGevity @lungoncdoc @weldeiry @OTtheScientist @PareshKumaaar @ktgminton @IUCancerCenter @MoffittNews @OncLive @OncoAlert @oncodaily @LungCancerRx @triparnasen @AparGanti @StephenVLiu

Today, @AmgenOncology issued the press release for DeLLphi-305, the Phase 3 study of tarlatamab in the 1L maintenance setting with durvalumab, compared to durvalumab alone for extensive-stage SCLC. The study met its primary endpoint at a pre-specified interim analysis demonstrating improvements in OS, along with PFS and ORR, with the addition of a DLL3xCD3 bispecific T-cell engager (TCE) to 1L maintenance. While this represents an unprecedented outcome for our SMASHERS impacted by ES-SCLC, and one step closer to changing the history of SCLC, several questions remain to be addressed: 1️⃣ Access: Progress only matters IF we can get therapies to those who need it. What about our SMASHERS all over the world who have not yet had access to tarlatamab for 2L and beyond? How long will 1LM take to implement? How can we work together to provide equitable access to all? Tarlatamab was approved in the US for accelerated use on May 16, 2024, yet our patients globally still cannot access it in most countries outside of a trial. 2️⃣ Support: With novel therapeutics such as TCEs in SCLC, maximized support to proactively recognize side effects will be key to ensure patients are living WELL for years on treatment. CRS, ICANS, and dysgeusia require aggressive multiD support to mitigate and manage. 3️⃣ Personalization of care: Biomarker discovery for tarlatamab, beyond DLL3, is needed. We must identify WHO will benefit from intensification of 1L maintenance, vs can avoid potential time, treatment, and financial toxicities. @SclcSMASHERS @LUNGevity @LungCancerEu @lcrf_org @GO2forLungCancr @SCLCYIForum

@BalazsHalmosMD @KolPulseAI @BalazsHalmosMD waiting for ADAURA data like… https://t.co/z46iTY3KWa

Fierce patient advocate and lung cancer survivor @jillfeldman4 asking key questions on the implementation of ADAURA at @IASLC #WCLC26 @EGFRResisters @EgfrUk @EGFRSummit @LUNGevity @lcrf_org @DrRoyHerbst @lungoncdoc @StephenVLiu @NarjustFlorezMD https://t.co/2racmdz8SC

Dr. Roy Herbst @DrRoyHerbst @dartmouth presents the updated 8Y OS follow up analysis of ADAURA for 3Y of adjuvant osimertinib in EGFR mutant NSCLC. Benefit in OS across all stages investigated IB-IIIA. Supportive management of toxicities and quality of life are key factors to ensuring patients can stay on therapy for 3Y. @EGFRResisters @EgfrUk @jillfeldman4 @lungoncdoc @LUNGevity @RManochakian @LauraAlderMD

Dr. Laura Alder @LauraAlderMD @DukeCancer details the first-line therapies for #SCLC at #DCLung26, including chemoIO, IMforte, and DeLLphi-303/305, and ADCs. @StephenVLiu @Joshua_Reuss @lungoncdoc @NouraChoudhury @SclcSMASHERS @SCLCYIForum https://t.co/VymnkTFej3

Dr. Julia Rotow @JuliaRotow presents the DESTINY-Lung-04 data of trastuzumab deruxtecan vs pembro+chemo in 1L HER2 NSCLC at @IASLC #WCLC26. T-DXd improved PFS and ORR, yet OS benefit is limited with this regimen, likely confounded by access to 2L HER2-directed therapies. AEs notable with ILD 20.8% (>4% G3+). Difficult to know how T-DXd will fit in the sequencing of an evolving HER2 landscape with available TKIs zongertinib & sevabertinib. @lungoncdoc @LUNGevity @LungCancerEu @YoungLungCancer @GO2forLungCancr @StephenVLiu

Dr. Alexander Drilon @alexdrilon presents the ARROS-1 study with zidesamtinib (NVL-520) in treatment naive ROS1+ NSCLC at @IASLC #WCLC26. Outstanding ORR 94% (15%) with mPFS not reached. Significant intracranial efficacy observed with sparing TRK inhibition. Toxicity notable for peripheral edema, neuropathy, and GI tox. New 1L agent for ROS1+ NSCLC? Waiting future OS data for this exciting agent. @ros1cancer @MSKCancerCenter @LUNGevity @OncoAlert @oncodaily @OncBrothers @lungoncdoc

Dr. Giannis Mountzios @g_mountzios presented at @IASLC #WCLC26 the EVOKE-03 Phase 3 study investigating sacituzumab govitecan (SG) + pembrolizumab vs pembrolizumab alone in PD-L1 >50% NSCLC. Unfortunately, while there was an improvement in PFS, ORR, and DCR, no significant improvement in OS was observed. Unclear what the rates of oncogenic drivers and co-alterations here were amongst the patients included in this study. Difficult to improve outcomes with adjunct therapies in PD-L1 high NSCLC. More research is needed for additional therapeutic targets in this patient population to improve outcomes and prevent recurrence/resistance. @LUNGevity @LauraAlderMD @lungoncdoc @BrunaPellini @RManochakian @StephenVLiu @FordePatrick @FSkoulidis

Dr. Chul Kim @chulkimMD expertly presenting the final OS results of PAPILLON investigating the role of amivantamab+chemo vs chemo in 1L EGFR exon 20 insertion positive NSCLC at @IASLC #WCLC26. Not significant difference in OS due to 76% crossover, but additional IPCW-adjusted analysis with HR 0.57 (P = 0.003). Longest survival data for exon20ins EGFR to date! @EGFRResisters @EgfrUk @jillfeldman4 @Exon20Group @lungoncdoc @LUNGevity @YoungLungCancer

Dr. Li Zhang presents the TAISHAN-302 Phase 3 study of Tam-Peli B7-H3 ADC (YL201) following at least one line of therapy compared to topotecan for ES-SCLC at @iaslc #WCLC26. Significant improvement in OS, PFS, ORR, and intracranial disease control. ILD 4.9% with YL201. This represents the Phase 3 with a B7-H3 ADC with improvement in outcomes over topotecan, however China only study. Publication is now available in NEJM today. It will be of great interest to understand how multiple B7-H3 available in pipelines will be of value to our patients impacted by SCLC globally. @SclcSMASHERS @LUNGevity @LungCancerEu @Lung_Cancers @OncoAlert @OncLive @StephenVLiu @lungoncdoc @RManochakian @OncBrothers