Advanced Non-squamous Non-small Cell Lung Research Articles

A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

Bevacizumab with platinum doublet therapy including paclitaxel+carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel+carboplatin led to Grade>3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel+carboplatin + bevacizumab combination in a Japanese population. Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6cycles of carboplatin (area under the concentration-time curve=6 on Day 1)+nanoparticle albumin-bound paclitaxel (100mg/m2 on Days 1, 8 and 15)+bevacizumab (15mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel+bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade≥3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

Anlotinib in Chinese patients aged ≥70 years with advanced non-squamous non-small cell lung cancer without prior chemotherapy: a multicenter, single-arm pilot trial.

Based on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed. This multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS). Forty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%). Anlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.

Abstract CT284: A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2

Abstract Background: First-line (1L) standard of care for patients with HER2 mutation-positive (HER2m+) non-small cell lung cancer (NSCLC) is platinum-based chemotherapy ± immunotherapy. To date, no targeted 1L treatments have been approved. Zongertinib is a HER2-selective tyrosine kinase inhibitor that binds to wild-type and mutated HER2, and spares EGFR. In Phase Ia of Beamion LUNG-1 (NCT04886804), zongertinib conferred objective response/disease control rates of 49/91% in patients with pretreated HER2 aberration-positive solid tumors, and 58/97% in those patients with HERm+ NSCLC, with manageable safety with few EGFR-associated adverse events. Purpose: Here we describe Beamion LUNG-2 (NCT06151574), a phase 3, randomized, controlled, open-label trial that will compare the efficacy and safety of 1L zongertinib with standard of care in patients with HER2m+, locally advanced/metastatic nonsquamous NSCLC. Experimental design: Approximately 270 patients will be randomized 1:1 to receive either zongertinib or standard of care. Key inclusion criteria: histologically/cytologically diagnosed advanced/metastatic nonsquamous NSCLC; no prior systemic treatment for locally advanced/metastatic disease; HER2 mutation in the tyrosine kinase domain; ≥1 measurable lesion (RECIST 1.1). Key exclusion criteria: tumors that have alterations with available therapy, and radiotherapy/major surgery ≤4 weeks prior to randomization. In the experimental arm, oral zongertinib 120 mg once daily will be given in 21-day cycles. In the comparator arm, intravenous pemetrexed 500 mg/m2 chemotherapy plus either cisplatin 75 mg/m2 or carboplatin area under the curve 5, plus pembrolizumab 200 mg will be given on day 1 every 3 weeks for 4 cycles, followed by pemetrexed 500 mg/m2 plus pembrolizumab 200 mg every 3 weeks for ≤35 cycles. In both arms, treatment will continue until progressive disease (RECIST 1.1), undue toxicity, or other criteria are met. Primary endpoint: progression-free survival (RECIST 1.1). Secondary endpoints: overall response (defined as best overall response of complete or partial response, RECIST 1.1), patient-reported outcomes (changes from baseline to Week 25), overall survival, and adverse events during the on-treatment period (CTCAE 5.0). Citation Format: Yi-Long Wu, Melissa Johnson, Ross Soo, Navid Baktash, Daniela Maier, Sabina Eigenbrod-Giese, Tatsuya Yoshida. A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT284.

Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer

Aims To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. Methods Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%–10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials’ median PFS were also conducted. Results In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. Conclusion Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study

BackgroundOsimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant.Method/designA total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12.Trial registrationChina Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed

PurposeThe aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. MethodsThe outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). Results1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). ConclusionsFirst-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

104TiP Phase Ib/IIa study of ATR inhibitor tuvusertib + anti-PD-1 cemiplimab in patients with advanced non-squamous (nsq) non-small cell lung cancer (NSCLC) that has progressed on prior anti-PD-(L)1 and platinum-based therapies

104TiP Phase Ib/IIa study of ATR inhibitor tuvusertib + anti-PD-1 cemiplimab in patients with advanced non-squamous (nsq) non-small cell lung cancer (NSCLC) that has progressed on prior anti-PD-(L)1 and platinum-based therapies

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

Cost-Effectiveness Analysis of Sintilimab Plus Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer: A Societal Perspective.

The updated ORIENT-11 study demonstrated that sintilimab, when combined with chemotherapy, had promising survival advantage compared to standard chemotherapy alone in the first-line treatment for previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC). This study aims to evaluate the cost-effectiveness of sintilimab plus chemotherapy for advanced nsNSCLC from a Chinese societal perspective. A partitioned survival model with aembedded decision tree was developed to assess the economic value of sintilimab plus chemotherapy over a lifetime horizon. Clinical data was captured from the updated ORIENT-11 study, while costs, health productivity losses, and utility values were collected from a nationwide cross-sectional survey in tertiary hospitals across multiple provinces in China. The primary outcomes were measured using the metrics of quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Costs and health outcomes were discounted at an annual rate of 5% per annum. Sensitivity analyses, including one-way and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses, were performed. Compared to standard chemotherapy, treatment with sintilimab plus chemotherapy incurred a mean total cost of $23,979 and gained 0.98QALYs over the lifetime horizon, resulting in an ICER of $24,568 per QALY gained. The use of sintilimab accumulated direct non-medical costs of $9262 and indirect costs of $6780 over 16years. Probabilistic sensitivity analyses showed an 84.2% probability of sintilimab plus chemotherapy being cost-effective at a threshold of three times China's per capita gross domestic product in 2022 ($38,201). The model was most sensitive to the discount rate of QALYs and costs, as well as the costs of pemetrexed, sintilimab, and subsequent therapy in progressive disease state. Subgroup analyses indicated favorable incremental net monetary benefits in all subgroups. Sintilimab plus chemotherapy is a cost-effective first-line treatment therapy for advanced nsNSCLC in China when compared to standard chemotherapy. These findings, along with the improved progression-free survival and overall survival (OS)observed in ORIENT-11, support the use of this regimen in eligible candidates for advanced nsNSCLC.

Clinical outcomes and medical resource utilization of toripalimab combination therapy versus bevacizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer

Objective This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China. Methods Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled. Results Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p < .001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p < .0001) and AE-related costs ($4,500.2 vs. $784.4, p < .0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p < .0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%). Conclusion Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs.

First-line treatments for advanced non-squamous non-small cell lung cancer with immune checkpoint inhibitors plus chemotherapy: a systematic review, network meta-analysis, and cost-effectiveness analysis.

The combination of immune checkpoint inhibitors (ICIs) and chemotherapy is a promising first-line therapy for patients with advanced non-squamous non-small cell lung cancer (NSCLC). The cost-effectiveness of combinations with different ICIs is yet to be compared. We utilized Bayesian network meta-analyses for the comparisons of overall survival, progression-free survival, and incidence of adverse events of the included treatments in the total population and subgroups with different programmed death-ligand 1 tumor proportional scores (TPS). The cost-effectiveness of the treatments from the perspectives of the US and Chinese healthcare systems was assessed using Markov models. Three combinations, including pembrolizumab + chemotherapy (PembroC), nivolumab + ipilimumab + chemotherapy (NivoIpiC), and atezolizumab + chemotherapy (AteC), were included in our study. In terms of efficacy, PembroC was most likely to be ranked first for extending progression-free survival (PFS) (93.16%) and overall survival (OS) (90.73%). Nevertheless, from the US perspective, NivoIpiC and PembroC showed incremental cost-effectiveness ratios (ICERs) of $68,963.1/quality-adjusted life-years (QALY) and $179,355.6/QALY, respectively, compared with AteC. The one-way sensitivity analysis revealed that the results were primarily sensitive to the hazard ratios for OS or the cost of immunotherapy agents. At a willingness-to-pay (WTP) threshold of $150,000/QALY, NivoIpiC had the highest probability of being cost-effective (63%). As for the Chinese perspective, NivoIpiC and PembroC had ICERs of $145,983.4/QALY and $195,863.3/QALY versus AteC, respectively. The results were primarily sensitive to the HRs for OS. At a WTP threshold of $38,017/QALY, AteC had the highest probability of cost-effectiveness (94%). Although PembroC has the optimal efficacy, NivoIpiC and AteC were the most favorable treatments in terms of cost-effectiveness for patients with advanced non-squamous NSCLC from the US and Chinese perspectives, respectively.

Effect of the thyroid transcription factor 1 expression and treatment discontinuation due to adverse events on progression-free survival in patients with advanced non-squamous non-small cell lung cancer treated with pembrolizumab plus pemetrexed and platinum chemotherapy: a Japanese four-hospital, retrospective study.

Although a significant improvement in progression-free survival (PFS) has been reported in the thyroid transcription factor 1 (TTF-1) positive patients under treatment for non-squamous non-small cell lung cancer (NS-NSCLC), including immune checkpoint inhibitor therapy, the association between TTF-1 expression and adverse event occurrence remains unclear. Therefore, this study investigated the impact of TTF-1 and its adverse events on PFS during pembrolizumab plus pemetrexed and platinum chemotherapy for NS-NSCLC. Patients who received the pembrolizumab plus pemetrexed and platinum chemotherapy from 1/1/2018 to 12/31/2022 and whose TTF-1 expression was measured were included in the study. This was a retrospective study conducted using electronic medical records. The mean age of the 79 patients was 67.5 ± 8.4 years, with 75.95% patients being male. Among them, 59.49% were TTF-1 positive. PFS comparison between TTF-1-positive and -negative patients showed a trend toward longer PFS for TTF-1 positive patients, though the results were statistically insignificant (P = 0.190). Proportional hazards analysis indicated significant PFS extension from treatment interruption, as adverse events related to cancer therapy stopped (hazard ratio [HR] = 0.32, P = 0.005) and the number of anticancer agents used (HR = 0.01, P < 0.001). Additionally, pembrolizumab plus pemetrexed and platinum chemotherapy for TTF-1-positive NS-NSCLC significantly extended PFS after treatment discontinuation as related adverse events stopped (827 vs. 210 days, P = 0.021). Measurement of TTF-1 may accordingly serve as a predictor of treatment response to the pembrolizumab plus pemetrexed and platinum chemotherapy. It may also be a predictor of patient prognosis when treatment is discontinued due to related adverse events.

Effect of AGEs-RAGE system on the efficacy of PD-1 inhibitors in the treatment of driver-gene mutation negative advanced non-squamous non-small cell lung cancer.

To observe the therapeutic effect of PD-1 inhibitors on driver-gene mutation negative advanced non-squamous non-small cell lung cancer (nsNSCLC) and the role of the AGEs-RAGE system in the disease, provide more reliable treatment for future nsNSCLC patients. In this study, we selected 130 nsNSCLC patients admitted between January 2021 and April 2022 were selected as the study subjects, 61 of whom received pemetrexed plus carboplatin (control group) and 69 received PD-1 inhibitors, pemetrexed and carboplatin (research group). The clinical efficacy and adverse reactions of the two groups were compared, and the prognostic survival time was calculated. The results show that two groups were not statistically different in objective response rate (ORR) and incidence of adverse reactions, but the disease control rate (DCR) was higher in the research group (P<0.05). Besides, the median progression-free survival (PFS) was prolonged in the research group compared with the control group (P<0.05). In addition, changes in the levels of T lymphocyte subsets, AGEs and RAGE before and after treatment were detected, and the relationship between AGEs-RAGE and the therapeutic effect of PD-1 inhibitors was analyzed. The research group also showed higher CD3+, CD4+ and lower CD8+, AGEs and RAGE levels than the control group after treatment (P<0.05). Finally, we found that in addition, the efficacy of the study group was inversely related to AGEs and RAGE levels (P<0.05). With these results, we concluded that PD-1 inhibitors are effective in the treatment of driver-gene mutation negative advanced nsNSCLC, and the AGEs-RAGE system may provide a more reliable guarantee for the treatment outcomes of patients in the future.

74P A single-center, phase II study of surufatinib combined with toripalimab, pemetrexed(A), and platinum (P) in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC)

74P A single-center, phase II study of surufatinib combined with toripalimab, pemetrexed(A), and platinum (P) in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC)

541P Integrated analysis of randomized controlled trials IMpower130 and IMpower132 for advanced non-squamous non-small cell lung cancer (NSCLC)

541P Integrated analysis of randomized controlled trials IMpower130 and IMpower132 for advanced non-squamous non-small cell lung cancer (NSCLC)

EP12.01-33 Liquid Biopsy Reduce Time to Treatment for Patients with EGFR mutated Advanced Nonsquamous Non-small Cell Lung Cancer : A Mexican Unit Experience

EP12.01-33 Liquid Biopsy Reduce Time to Treatment for Patients with EGFR mutated Advanced Nonsquamous Non-small Cell Lung Cancer : A Mexican Unit Experience

Comparison of Efficacy and Safety of a Bevacizumab Biosimilar, in Combination with Chemotherapies, in Nonresectable Metastatic Colorectal Cancer and in Advanced Nonsquamous Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study.

Ranjith K.The objective of this study was to compare the efficacy, safety, pharmacokinetics, and immunogenicity of a proposed bevacizumab biosimilar (DRL_BZ) with the innovator Avastin (reference medicinal product [RMP]) in patients with nonresectable metastatic colorectal cancer (mCRC) over a period of 9 months and advanced nonsquamous non-small cell lung cancer (NSCLC) over 6 months. The study was planned as a randomized, double-blind trial. In part A, a total of 117 mCRC patients were intended to receive 5 mg/kg of bevacizumab every 2 weeks along with mFOLFOX6 chemotherapy for a maximum of 18 cycles. In part B, 60 NSCLC patients were to receive 15 mg/kg of bevacizumab every 3 weeks along with pemetrexed and carboplatin for the initial four cycles, followed by pemetrexed for another four cycles. The primary endpoint was the progression-free survival rate at 6 months (PFS6) in both subparts. The anticipated sample size was 106 evaluable mCRC patients to achieve 85% statistical power for concluding noninferiority with a margin of half the difference (18.8%) between DRL_BZ and Avastin, along with a pilot study involving 60 evaluable NSCLC patients. Safety comparison included assessing adverse events (AEs), infusion reactions, and lab abnormalities. Immunogenicity comparison involved the incidence of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs). Pharmacokinetic comparison was planned after the first and fourth dosing cycles of treatment in 24 NSCLC patients. The PFS6 for mCRC patients treated with DRL_BZ and RMP was 57.8% and 50% respectively, with a difference in efficacy of 7.8 (-8.7, 23.7). The PFS9 was 31.1% and 22.9%, with a difference of 8.2% (-6.9%, 22.9%). The objective response rate (ORR) for DRL_BZ and RMP was 28.8% and 22.4%, while the disease control rate (DCR) was 44.2% and 37.9% respectively. For NSCLC patients, the PFS6 was 44% and 45%, showing a difference of -1.0 (-4.2, 22.1). The ORR was 41.4% and 48.1%, and the DCR was 62.1% and 63%. The frequency, type, and severity of AEs were similar in both indications. Blood levels during the first and fourth dosing cycles exhibited comparable values. All NSCLC patients tested negative for ADA, while no mCRC patients on DRL_BZ tested positive for ADA. Low incidences of ADA (8%) and NAbs (4.0%) were reported in patients on RMP. Overall, the efficacy, safety, immunogenicity, and pharmacokinetic parameters of DRL_BZ and RMP were found to be comparable. Clinical Trial Registration For BZ-01-002: CTRI/2016/01/006481.

A real-world study of recombinant human endostatin combined with PD-1/PD-L1 blockade and chemotherapy for patients with advanced non-small cell lung cancer negative for actionable molecular biomarkers.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. To evaluate the real-world efficacy and safety of endostar combined with immune checkpoint inhibitor and chemotherapy (EIC) for advanced non-squamous non-small cell lung cancer patients negative for actionable molecular biomarkers (NSCLCnm), patients with advanced NSCLCnm hospitalized to Zhejiang Provincial People's Hospital from January 2020 to December 2022 were screened for eligibility. The included patients were analyzed for the objective response rate (ORR) and disease control rate (DCR). The pre- and posttreatment expression levels of serum tumor associated biomarkers, chemokines and subpopulations of immune cells in peripheral blood were compared. For the 31 patients with advanced NSCLCnm treated with EIC, the median follow-up and treatment cycles were 18.0 months and 4, respectively. The ORR and DCR were 38.7% and 90.3%, respectively. For those who received EIC as first-line treatment, the ORR and DCR were 63.2% and 94.7%, respectively. EIC significantly decreased expression levels of carcinoma antigen 125, carcinoma embryonic antigen and cytokeratin 19 (P<0.05) in patients who were partial remission or stable disease. Among the 31 patients, 27 (87.1%) experienced at least 1 treatment-related adverse events, and 13 (41.9%) had the treatment-related adverse events of grade 3 or higher. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.

LBA63 SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC)

LBA63 SAPPHIRE: Phase III study of sitravatinib plus nivolumab versus docetaxel in patients with previously treated advanced non-squamous non-small cell lung cancer (NSCLC)

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03