#WCLC20 Excited about this one: phase I results of the HER3 ADC patritumab deruxtecan (HER3-DXd; U3-1402) in #EGFR mutant #NSCLC presented by @HelenaYu923 #LCSM @IASLC @OncoAlert
#WCLC20 Presentation here is on the combined dose escalation and expansion at the 5.6 mg/kg dose with #EGFR mutant NSCLC. Includes 56 evaluable patients. Median f/u 5 months. #LCSM @IASLC
#WCLC20 Fairly heavily pretreated population with both TKI and chemotherapy and many with IO as well. Biopsy required for HER3 expression (violin plot on right) and nearly all were HER3 positive. #LCSM
#WCLC20 Impressive responses given the number of different resistance mechanisms represented in this heavily pretreated population. 55% with treatment ongoing. Most with some reduction. #LCSM
#WCLC20 Responses here tended to be quick, some very deep (CR noted). The reported RR was 25% with a DCR of 70%, time to response 2m, duration of response 6.9m. Encouraging data here. #LCSM
#WCLC20 As with many ADCs, common toxicities include myelosuppression (28% G3 plt, 19% G3 ntp). Interstitial lung disease noted in 3 patients (5%). Phase 3 HERTHENA-Lung 01 study ongoing. Keep an eye on this agent to possibly fill a huge unmet need. #LCSM

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More from @StephenVLiu

29 Jan
#WCLC20 CHRYSALIS trial results with amivantamab in #EGFRex20 NSCLC post-platinum based chemotherapy presented by @JSabari. Amivantamab has FDA breakthrough designation for this indication. @IASLC #LCSM @OncoAlert
#WCLC20 Amivantamab is an EGFR-MET bispecific antibody given intravenously weekly x 1 month then q2w. This is a single arm phase II for patients with #EGFRex20 mutant NSCLC after prior chemotherapy. #LCSM
#WCLC20 Amivantamab was reasonably well tolerated. G3 TEAE in 35% but treatment-related rate only 16%. Drug related AE leading to discontinuation only 4%. Mostly G1-2 adverse events including rash, paronychia. #LCSM
Read 4 tweets
29 Jan
#WCLC20 Dr. Nakagawa presents results from the DESTINY-Lung01 trial of trastuzumab deruxtecan (T-DXd, Enhertu). T-DXd is a HER2 antibody-drug conjugate (ADC). #LCSM @IASLC @OncoAlert
#WCLC20 This study had two cohorts. Here, we focus on Cohort 1 (HER2-overexpressing = IHC3+ or IHC2+). Primary response rate was ORR. #LCSM
#WCLC20 As a reminder, we saw results from Cohort 2 (HER2-mutant) at #ASCO20 where they reported an ORR of 61.9% with mPFS 14.0m, which led to the inclusion of T-DXd in the @NCCN guidelines for #HER2 mutant NSCLC. #LCSM
Read 8 tweets
29 Jan
#WCLC20 Highly anticipated results of oral TKI mobocertinib (TAK-788) in #EGFRex20 mutant NSCLC after prior platinum based chemotherapy. Huge unmet need and as @Jbauml reported at this meeting, likely underdiagnosed. #LCSM @IASLC @OncoAlert
#WCLC20 Cohort being discussed here is #EGFR exon 20 insertion NSCLC after prior platinum therapy and the EXCLAIM extension cohort. Many patients also had prior TKI therapy and prior immunotherapy. @IASLC
#WCLC20 Here are the topline results. RR 23-26% by IRC, RR 32-35% by investigator, DOR by IRC was 17.5m (!) and mPFS 7.3m -- for #EGFRex20, no clear standard. Mobocertinib certainly has some activity here. #LCSM
Read 6 tweets
29 Jan
#WCLC20 Results from the phase III non-inferiority J-AXEL study of salvage nab-paclitaxel vs docetaxel in NSCLC. Large study (n>500) with a 1:1 randomization. #LCSM @IASLC @OncoAlert
#WCLC20 Positive study! Shows non-inferiority in OS with nab-paclitaxel over docetaxel (median 16.2m vs 13.6m). PFS favors nab-pac (HR 0.76). #LCSM
#WCLC20 RR favors nab-paclitaxel (30% vs 15%) and in this study, unlike the registrational trial, no real difference between squamous and non-squamous (both 30%, both better than docetaxel). #LCSM
Read 4 tweets
29 Jan
#WCLC20 Results from phase I study of the TROP2 ADC datopotamab deruxtecan (Dato-DXd; DS-1062) in NSCLC by @AlexSpiraMDPhD #LCSM @IASLC @OncoAlert
#WCLC20 This ADC includes an anti-TROP2 IgG1 and a topo-1 inhibitor payload. Phase 1 design shown here. Mostly non-squamous, included some #EGFR+, heavily pretreated including many with CNS metastases. Less intensity at higher 8mg dose, as one would expect. #LCSM
#WCLC20 Safety shown here and manageable but I would say still notable, especially at 8mg (G3+ AEs 34%) including ILD noted in 8% (but 3 grade 5 cases in the 8mg/kg cohort). #LCSM
Read 5 tweets
29 Jan
#WCLC20 Results from randomized phase II of nivo vs nivo/ipi in #EGFR mutant NSCLC. Unfortunately, study stopped for futility (n=31) but glad to see results presented. #LCSM @IASLC
#WCLC20 Only 1 response (RR 3%) and median PFS of 1.3 months. Spider plot shows some with modest duration stable disease (but others with rapid progression - suggestive of TKI flare?) #LCSM
#WCLC20 Treatment was well tolerated - we are concerned about safety when TKI follows immunotherapy, not really the other way around (as done here). #LCSM
Read 5 tweets

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