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Stephen V Liu, MD

@StephenVLiu

Aug 8, 2020 • 7 tweets • 5 min read • Read on X

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@JTOonline

#OncoAlert Online now @JTOonline is the ORIENT-11 trial of sintilimab + platinum/pemetrexed in NSCLC. Simultaneous publication with #VPS20 #WCLC20 @IASLC presentation. Randomized phase III study of chemotherapy +/- anti PD-1 antibody sintilimab. #LCSM

jto.org/article/S1556-…

Sintilimab is a PD1 antibody and the phase Ib of sintilimab with platinum/pem had RR 68.4% and mPFS 11.4m. Phase III included 397 patients in 47 hospitals in China with treatment naive advanced EGFR/ALK wild type non-squamous NSCLC, stratified by PDL1 expression (22C3).

Enrolled in < 1y! All patients received 4 cycles of carboplatin AUC 5 with pemetrexed 500mg/m2 q21d and randomized 2:1 to sintilimab 200mg flat dose or placebo followed by sintilimab/placebo maintenance. After median f/u of 8.9m, primary endpoint met: PFS 8.9m vs 5m (HR 0.482).

Early split and no crossing of curves, very comparable to KEYNOTE-189. Benefit across major subgroups (including non-smokers), stepwise benefit by PDL1 expression. Consistent results; good to demonstrate in East Asian population (only 1% of patients receiving pembro in KN189).

Benefit seen across PDL1 strata. In PDL1 negative, PFS 7.3 vs 5.1m (HR 0.664). In PDL1 low, PFS 7.1 vs 4.8 (HR 0.503). In PDL1 high, PFS NR vs 5m (HR 0.310). RR higher with sintilimab(51.9% vs 29.8%) and median time to response 1.5m.

No worrisome safety signals with comparable G3+ toxicity in both arms (primarily due to chemotherapy). Discontinuation of sintilmab due to AE seen in 6% (vs 8.4% in placebo arm). irAEs in 43.2% with sintilmab and 36.6% with placebo (blinded study), but mostly G1-2.

@IASLC

OS is immature with medians not reached but HR 0.609 trending to favoring sintilimab. Crossover permitted but only 31.3% in control arm crossed over to sintilimab (another 4.6% received an alternate immunotherapy). #LCSM #OncoAlert @IASLC @JTOonline

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More from @StephenVLiu

Stephen V Liu, MD

@StephenVLiu

Sep 8

Dr. @marinagarassino at #WCLC24 Presidential Plenary presents Normalized Membrane Ratio of TROP2 as a biomarker for datopotamab deruxtecan in TROPION-Lung01 (Dato-DXd vs docetaxel in previously treated NSCLC which previously showed PFS benefit with Dato-DXd.

#WCLC24 TROP2 IHC has been a poor predictive marker. Normalized Membrane Ratio (NMR) factors in receptor internalization. Ratio is membrane expression over membrane plus cytoplasmic expression (using optical density from digitized slide) and lower would be more favorable.

#WCLC24 TROP2 QCS-NMR seems to be a much better predictor of benefit with datopotamab deruxtecan in BEP and in non-sq non-AGA subset: in NMR+, PFS HR 0.57 and KM shows clear separation.

Read 4 tweets

Stephen V Liu, MD

@StephenVLiu

Apr 23, 2023

Dr. Shun Lu presents interim results from the perioperative NEOTORCH study at the #ASCOPlenarySeries. Randomized pts with resectable stage II/III NSCLC to perioperative chemotherapy with toripalimab (anti-PD1) vs placebo. Another entry in the perioperative space? #LCSM

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

First interim EFS analysis only for stage III. Includes 404 pts - but 926 screened. Would be interesting to see specific eligibility criteria not met in screening process. Reminder of how selected trial populations are and value of future real-world analyses. #ASCOPlenarySeries

Read 11 tweets

Stephen V Liu, MD

@StephenVLiu

Apr 16, 2023

Impressive data from #AEGEAN at #AACR23 from Dr. John Heymach and colleagues. This is the first of several phase III peri-operative IO studies in resectable NSCLC combining neoadjuvant chemo-immunotherapy followed by adjuvant immunotherapy.

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.

Almost 75% received carboplatin over cisplatin. Global study; fairly even PDL1 distribution. 80% of pts went to surgery, 78% completed resection (90-95% of those were R0). Overall, 66% of pts began adjuvant phase (but 90% of those who had an R0 resection had adjuvant therapy).

Read 9 tweets

Stephen V Liu, MD

@StephenVLiu

Dec 8, 2022

There is a lot to consider in this first-line study of the #KRAS G12C inhibitor adagrasib plus pembrolizumab from #ESMOImmuno22. Some pleasant surprises in terms of safety. Definitely encouraging but need to see a bit more to be sold on this strategy. 🤔 #LCSM

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

The first-line dataset includes the phase Ib KRYSTAL-1 and the phase II KRYSTAL-7. In KRYSTAL-1 (n=7), 4/7 had a response and all were durable (>9m). G3 TRAEs in 4 pts (lipase elevation, LFTs, muscular pain, pneumothorax). #ESMOImmuno22

Read 10 tweets

Stephen V Liu, MD

@StephenVLiu

Sep 19, 2022

@ZPiotrowskaMD

Dr. @ZPiotrowskaMD presents initial results from the ELIOS trial at #ESMO22 - molecular profiling of #EGFR mutant NSCLC after progression on 1L osimertinib.

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

Common co-mutations at baseline included TP53, EGFR amp, and CDKN2A loss. Acquired alterations included MET amp, EGFR C797S, ALK fusion, NKX2-1 amp. Mostly mutually exclusive. #ESMO22

Read 5 tweets

Stephen V Liu, MD

@StephenVLiu

Sep 11, 2022

Dr. Silvia Novello presents 5y update on KEYNOTE 407 (platinum plus tax and +/- pembrolizumab for 1L squamous NSCLC #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

For patients who complete 2y of pembrolizumab, 3y OS rate (after completing 2y pembro) was 70% - though not all of those patients are cured (44% were alive without PD or subsequent therapy). #ESMO22

Read 4 tweets

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