Director of Thoracic Oncology & Developmental Therapeutics @Georgetown @LombardiCancer; Host @IASLC Podcast; Chair #TexasLung24 #PLCCLive24 #DCLung24 #HereWeGo
Includes resectable stage II/III (AJCC v8), EGFR/ALK wild type NSCLC. Pts receive 3 cycles of neoadjuvant chemotherapy + toripalimab vs placebo then surgery then 1 more cycle of adjuvant chemo (+tori/pbo) then 13 doses of maintenance toripalimab vs placebo. #ASCOPlenarySeries 
Included stage IIA-IIIB (AJCC v8) with no EGFR/ALK & excluded pts who would require pneumonectomy. Large study with n=801 (CM816 was n=358). Pts received 4 cycles (not 3) of platinum-based chemo with durvalumab (anti-PDL1) or placebo, then surgery, then durvalumab / placebo x 1y. 
We're looking for synergy with the two agents - more than an additive effect. Reason to believe there will be based on preclinical data showing the effect on T-cell infiltration from #KRAS inhibition. Similar to what has been shown with MEK inhibition. #ESMOImmuno22 
In this study of highly motivated pts at esteemed sites, evaluable paired biopsy at PD only available in 46/115 pts (40%). Interestingly, 75 pts (65%) had paired biopsy but 27 failed NGS (23%). Speaks somewhat to the real world feasibility of a repeat biopsy approach. #ESMO22 
With longer follow up, OS favors pembrolizumab arm with mOS 17.2 vs 11.6m (OS HR 0.71) in squamous NSCLC. 5y OS rate 18.4% vs 9.7%. PFS benefit (HR 0.62) and higher RR across PDL1 strata. #ESMO22 
KEYNOTE 189 is our SOC and has shown a consistent benefit including improving OS even with a crossover rate of 57%. #ESMO22 
Study design here shows randomization to first-line sintilimab + anlotinib or chemo (with sintilimab at progression). Some concerns about randomization to chemotherapy without immunotherapy in a modern day study. #ESMO22 
Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) targeting #HER2 and in DESTINY-Lung01, RR was encouraging at 55% but some concern for toxicity (adjudicated drug-related ILD in 26% of cases). #ESMO22 
DESTINY-Lung02 compared two doses of trastuzumab deruxtecan (T-DXd) in #HER2 previously treated NSCLC (5.4 mg/kg vs 6.4 mg/kg): RR 58% and DoR 8.7m at the lower dose compared to 43% at 6.4 mg/kg. #ESMO22 
The difference here is radiation and in T3/T4 NSCLC, local control is so critical. Largely unexplored to date. The INCREASE study explores quad-modality therapy and the results were quite impressive. High pCR rates and seen across PDL1 strata, not just in PDL1 high. #ESMO22 
Focus is on high T stage and low N stage - not resectable initially but potentially resectable after therapy. Patients here received nivo/ipi on day 1 and nivo on day 22 with chemoradiation then resection 6w later (after restaging) with pCR/MPR primary endpoint. #ESMO22 
@DrSanjayPopat @myESMO #ESMO22 @DrSanjayPopat points out that the DFS HR is on par with the original analysis but the shape of the curves is different, especially for stage II/III 
The DFS HR of 0.23 in resected stage II/III remains very impressive. But once osimertinib is stopped after 3y, the curves do seem to be coming closer together. DFS at 2y with osi is 90% and at 3y is 84% but drops to 70% at 4y. Are we preventing recurrence or delaying it? #ESMO22 
#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 This study had two cohorts. Here, we focus on Cohort 1 (HER2-overexpressing = IHC3+ or IHC2+). Primary response rate was ORR. #LCSM 
#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 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 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 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 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 
