Non-squamous Non-small Cell Lung Cancer Research Articles

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

P42-5 Efficacy and safety of camrelizumab and carboplatin and pemetrexed in advanced nonsquamous NSCLC: A systematic review

P42-5 Efficacy and safety of camrelizumab and carboplatin and pemetrexed in advanced nonsquamous NSCLC: A systematic review

Brief Report: Not Created Equal: Survival Differences by KRAS Mutation Subtype in NSCLC Treated With Immunotherapy

IntroductionThe predictive and prognostic implications of different KRAS mutation (KRASm) subtypes in metastatic NSCLC have not been clearly defined. We used a nationwide observational database to investigate whether KRASm subtypes differ in their association with survival in metastatic NSCLC treated with immune checkpoint inhibitor (ICI)-based therapy, across programmed death-ligand 1 (PD-L1) levels. MethodsPatients with advanced nonsquamous NSCLC who initiated first-line ICI-based therapy from 2016 to 2021 and had known PD-L1 expression and comprehensive genomic profiling including KRAS, STK11, KEAP1, and TP53 were included. Within PD-L1 expression subgroups (<1%, 1%–49%, ≥50%), Cox multivariable regression was used to evaluate the association between KRASm subtypes (G12C, G12V, G12D, other KRASm) and overall survival, estimated using Kaplan-Meier methodology. ResultsAmong the 1539 patients, 819 patients were KRAS wild type (KRASwt) and 720 were KRASm (296 KRAS G12C, 143 KRAS G12V, 97 KRAS G12D, 184 other KRASm). In the 50% or higher PD-L1 subgroup, patients with KRAS G12V had worse survival (median overall survival [mOS] = 8.2 mo) compared with KRASwt (mOS = 13.3 mo) and other KRAS subgroups (mOS ranging from 13.4 to 19.9 mo). On adjusted Cox multivariable regression in the 50% or higher PD-L1 subgroup, the hazard ratio for death for KRAS G12V ranged from 1.53 to 1.78 compared with KRASwt and other KRASm subtypes (all p < 0.05). ConclusionsAlthough patients with 50% or higher PD-L1 with KRAS G12C, G12D, and other subtypes exhibited similar survival to KRASwt, KRAS G12V was associated with significantly worse survival than KRASwt and other KRASm subtypes. All KRASm should not be regarded as uniform predictors of ICI responsiveness, even with high PD-L1 expression; KRAS G12V tumors may have worse outcomes with ICI-based therapy and benefit from treatment intensification.

OA11.05 Results of a Phase III Trial of Prolgolimab with Chemotherapy as First-Line Therapy for Patients with Advanced Non-Squamous NSCLC: DOMAJOR

OA11.05 Results of a Phase III Trial of Prolgolimab with Chemotherapy as First-Line Therapy for Patients with Advanced Non-Squamous NSCLC: DOMAJOR

OA08.05 Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial

OA08.05 Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial

EP.06G.13 TP53 Somatic Mutation and its Association with Clinicopathological Parameters and Long-Term Clinical Outcome in Non-Squamous NSCLC Patients

EP.06G.13 TP53 Somatic Mutation and its Association with Clinicopathological Parameters and Long-Term Clinical Outcome in Non-Squamous NSCLC Patients

P2.10B.01 Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03

P2.10B.01 Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03

Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.

Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE. We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated. Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death. The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the randomized Phase II PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab

BackgroundPERLA (NCT04581824) compared efficacy and safety of dostarlimab (DCT) or pembrolizumab (PCT) plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Here, we report patient-reported outcomes (PROs; exploratory analysis) from PERLA. MethodsPatients were randomized 1:1 to receive DCT or PCT every 3 weeks (Q3W) for ≤ 35 cycles [C]. PROs (EORTC QLQ-C30 and QLQ-LC13, PRO-CTCAE, FACT-GP5) were collected at baseline, Q3W until C4, Q9W until C16, Q12W until end of treatment and at 30-day safety follow-up. Change from baseline and time to deterioration (TTD) in QLQ-C30 and QLQ-LC13 were analyzed using longitudinal mixed models and Kaplan–Meier estimators, respectively. ResultsThe PRO (DCT/PCT) datasets included 102/99 patients for QLQ-C30, 96/90 for QLQ-LC13, 96/88 for PRO-CTCAE, and 95/87 for FACT-GP5. Completion rates were > 80 % to C4, then decreased in both arms. For QLQ-C30 and QLQ-LC13, most patients reported stable/improved responses at C13 (∼ 9 months on treatment), with similar responses between arms except more patients reported improvements in dyspnea (QLQ-C30: 36.4 % vs 13.0 %; QLQ-LC13: 40.6 % vs 25.0 %) and chest pain (QLQ-LC13: 34.4 % vs 10.0 %) with DCT vs PCT. TTD per QLQ-C30 and QLQ-LC13 were similar between arms, although TTD in dyspnea was longer with DCT vs PCT (QLQ-LC13: 4.24 vs 1.54 months; p = 0.0168). Most patients in both arms reported that adverse events occurred occasionally/rarely/never with moderate/mild severity. Overall, patients reported little/no bother from treatment side effects. ConclusionsDCT maintained health-related quality of life similarly to PCT and was well tolerated, supporting the PERLA primary results and dostarlimab use in future regimens.

Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients.

The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.

FLAIR: A Phase II, Open Label, Randomized Study of Osimertinib Plus Bevacizumab Versus Osimertinib in Recurrent or Metastatic Treatment-Naïve NSCLC Patients Harboring EGFR 21L858R Mutation

IntroductionOsimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation. Materials and MethodsFLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented EGFR exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety. ResultsFLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate). ConclusionsThis study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65years compared to those ≥ 65years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65years and male gender may experience greater benefits from perioperative IO-CT.

Efficacy and Safety of Biosimilar SCT510 Compared with Bevacizumab for the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study.

SCT510 is a biosimilar to bevacizumab (Avastin) reference product (RP) that is approved for various metastatic cancers. In this study, we aimed to demonstrate the equivalence of SCT510 and bevacizumab in terms of efficacy, safety, immunogenicity and pharmacokinetics (PK) in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients with non-squamous NSCLC were randomized equally to the SCT510 group (comprising SCT510, paclitaxel, and carboplatin) and the bevacizumab group (comprising bevacizumab, paclitaxel, and carboplatin) for 4-6 cycles, followed by maintenance monotherapy with SCT510. The primary endpoint was the objective response rate (ORR) at week 12. Secondary endpoints included 18-week ORR, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and 1-year survival rate, as well as assessments of safety, immunogenicity, and multi-dose PK analysis. Between March 29, 2019, and April 27, 2021, 989 patients were screened and 567 eligible patients were randomly assigned to the SCT510 group (285 patients) and the bevacizumab group (282 patients). The ORR at week 12 was 52.6% [95% confidence interval (CI) 46.66-58.55%] in the SCT510 group and 52.5% (95% CI 46.47-58.47%) in the bevacizumab group. The ORR at week 18 was 55.4% (95% CI 49.46-61.30%) for SCT510 and 55.7% (95% CI 49.68-61.62%) for bevacizumab. The ORR risk ratio (RR) at weeks 12 and 18 was 0.99 (90% CI 0.873-1.133) and 0.99 (90% CI 0.872-1.114), respectively, both within the pre-specified equivalence margin of 0.75-1.33. There were no differences between the two groups in relation to other secondary endpoints, specifically DCR, DOR, PFS, OS, and 1-year survival rate. The overall safety findings were similar between the two treatment groups, and both SCT510 and bevacizumab RP exhibited low immunogenicity. SCT510 is similar to bevacizumab in clinical efficacy, safety, immunogenicity, and PK in patients with advanced non-squamous NSCLC. The totality of the evidence supports the clinical equivalence of SCT510 and bevacizumab. NCT03792074.

1345P Surufatinib plus toripalimab combined with pemetrexed (A), and platinum (P) in patients (pts) with advanced non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results of a single-center, phase II trial

1345P Surufatinib plus toripalimab combined with pemetrexed (A), and platinum (P) in patients (pts) with advanced non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results of a single-center, phase II trial

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

1329P Fruquintinib combined with sintilimab and chemotherapy as the first-line treatment in advanced naïve EGFR- and ALK-negative non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results

1329P Fruquintinib combined with sintilimab and chemotherapy as the first-line treatment in advanced naïve EGFR- and ALK-negative non-squamous non-small cell lung cancer (nsq-NSCLC): Updated results

165P Consistency analysis of c-Met protein expression over time in patients with non-squamous non-small cell lung cancer

165P Consistency analysis of c-Met protein expression over time in patients with non-squamous non-small cell lung cancer

1311P Phase II, open-label study of frontline tusamitamab ravtansine with pembrolizumab ± chemotherapy in advanced non-squamous non-small cell lung cancer: Updated results from CARMEN-LC05 trial

1311P Phase II, open-label study of frontline tusamitamab ravtansine with pembrolizumab ± chemotherapy in advanced non-squamous non-small cell lung cancer: Updated results from CARMEN-LC05 trial

1257MO ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study

1257MO ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study

1312P Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): Results from TROPION-Lung01

1312P Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): Results from TROPION-Lung01