377 Background: PD-1 blockades combined with chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC recently. However, the safety profile of conventional chemotherapy was still disappointing. Therefore, the chemotherapy-free regimen might be a promising strategy. And it had been proved that PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) in second-line treatment for advanced ESCC showed potential efficacy and manageable toxicity. As a novel multitarget TKI mainly targeting VEGFR1-3, anlotinib was a potential first-line combination therapy and second-line monotherapy for patients with ESCC in China. TQB2450 was a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China), which is currently undergoing several clinical studies in China, involving ESCC and other solid tumors. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with TQB2450 as first-line therapy in advanced ESCC. Methods: Patients with previously untreated metastatic or locally advanced ESCC, whose age was between 18 and 75 years, with ECOG PS of 0 or 1 and life expectancy of more than 3 months were eligible as the inclusion criteria. Eligible patients were administered with anlotinib (12mg, po, d1~14, q3w) plus TQB2450 (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 and iRECIST using CT scans every 2 cycles for the first 6 cycles, and every 3 cycles thereafter. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 46. The primary endpoint was ORR. Secondary endpoints included safety, PFS, DCR, DoR and OS. Results: From Mar 2022 to Aug 2022, a total of 36 patients were enrolled, 23 patients included in per-protocol set. In best overall response assessment, there were 14 PR (60.9%), 8 SD (34.8%) and 1 NE (4.4%). In consequence, the preliminary ORR was 60.9% (95%CI: 38.5%~80.3%), DCR was 95.7% (95%CI: 78.1%~99.9%). No patients had disease progression at the date of data cutoff. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-related adverse events in 36 patients with the incidence >10% were hypertension (33%), fatigue (17%), decreased white blood cell count (14%), hyperthyroidism (11%) and decreased neutrophil count (11%). The common grade ≥3 treatment-related adverse events were decreased platelet count (3%) and decreased lymphocyte count (3%). Conclusions: Preliminary results suggested that anlotinib combined with TQB2450 as first-line therapy in advanced ESCC exhibited encouraging efficacy and manageable adverse events. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT05038813 .

No abstract

4041 Background: PD-1 blockades combined with chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC recently. However, the safety profile of conventional chemotherapy was still disappointing. Therefore, the chemotherapy-free regimen might be a promising strategy. As a novel multitarget TKI mainly targeting VEGFR1-3, anlotinib was a potential first-line combination therapy and second-line monotherapy for patients with ESCC in China. TQB2450 was a novel PD-L1 blockade developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Nanjing, China). Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with TQB2450 as first-line therapy in advanced ESCC. The preliminary results were reported in 2023 ASCO-GI Symposium (Abs 377) and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC, whose age was between 18 and 75 years, with ECOG PS of 0 or 1 and life expectancy of > 3 months were eligible as the inclusion criteria. Eligible patients were administered with anlotinib (12mg, po, d1~14, q3w) plus TQB2450 (1200mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 and iRECIST using CT scans every 2 cycles for the first 6 cycles, and every 3 cycles thereafter. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 46. The primary endpoint was ORR. Secondary endpoints included safety, PFS, DCR, DoR and OS. Results: From Mar 2022 to Sep 2022, a total of 46 patients were enrolled. At the data cut-off date (Dec, 2022), there were 1 CR (2.2%), 27 PR (58.7%), 14 SD (30.4%) and 4 NE (8.7%). Therefore, the preliminary ORR was 60.9% (95%CI: 45.4%~74.9%), DCR was 91.3% (95%CI: 79.2%~97.6%). The median PFS of the 46 pts was not yet available. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-related adverse events in 46 patients with the incidence > 10% were hypertension (28%), hypothyroidism (20%), leukocytosis (20%), hyperthyroidism (17%), anemia (15%), fatigue (15%), neutrophil count decreased (11%), constipation (11%), sinus bradycardia (11%) and hand-foot syndrome (11%). The common grade ≥3 treatment-related adverse events were hypertension (4%), hand-foot syndrome (2%), hyponatremia (2%), platelet count decreased (2%) and lymphocyte count decreased (2%). Conclusions: Preliminary results suggested that anlotinib combined with TQB2450 as first-line therapy in advanced ESCC exhibited encouraging efficacy and manageable adverse events. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT05038813 .

Background:The efficacy and safety of chemotherapy strategies combining the multi-target receptor tyrosine kinase inhibitor in patients with advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC) are undetermined. We aimed to investigate the efficacy and safety of anlotinib combined with carboplatin/pemetrexed-based chemotherapy followed by maintenance therapy (anlotinib plus pemetrexed) in advanced EGFR/ALK wild-type nsq-NSCLC.Methods: Eligible patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy in Henan Province from March 2019 to February 2021 were recruited. All patients were treated with anlotinib in combination with carboplatin/pemetrexed-based chemotherapy, followed by maintenance therapy (anlotinib plus pemetrexed). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), disease control rate (DCR), objective response rate (ORR), and adverse events (AEs). Response and AEs were assessed based on the Response Evaluation Criteria in Solid Tumors (1.1) and National Cancer Institute -Common Terminology Criteria for Adverse Events v.4.0.3, respectively. The follow-up interval for survival was 6 weeks and the safety follow-up was performed until the end of treatment. Kaplan-Meier analysis was used to calculate the median PFS and OS.Results: Thirty-eight participants with median age of 62 (range, 33-75) years were evaluated. Five participants were still on maintenance therapy until the end of the study. The majority were non-smokers (68.4%). The median follow-up was 13.6 (range, 12.3-14.9) months. The median PFS (mPFS) was 10.5 (95% CI: 4.1, 17.0) months, and the median OS was 23.4 [95% CI: not evaluable (NE), NE] months. The DCR and ORR were 94.7% and 60.5%, respectively. Grade 3 and above treatment-related adverse events (TRAEs) happened to 12 participants. The most common TRAEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow toxicity (10.5%). Seven patients discontinued treatment, including two patients during induction and five patients during maintenance treatment. No grade 5 TRAE was reported. In the nonsmoker participants, the mPFS was 14.5 (95% CI: 4.0-25.0) months.Conclusions: Anlotinib in combination with carboplatin/pemetrexed-based chemotherapy followed by anlotinib plus pemetrexed as maintenance therapy might be an effective choice in treating patients with wildtype EGFR/ALK advanced nsq-NSCLC.