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Background: Surufatinib (S, a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) plus toripalimab (T, an anti-PD-1 antibody) showed encouraging antitumor activity in solid tumors (Cao YS, 2022). Programmed death ligand 1 (PD-L1) expression is the established biomarker for 1L immune checkpoint inhibitors therapy in advanced NSCLC. We conducted an open-label, multi-cohort, single-arm phase 2 study to evaluate the safety and efficacy of S+T in patients (pts) with advanced solid tumors. Here, we reported the results of advanced NSCLC with PD-L1 positive expression cohort. Methods: Eligible pts had histologically confirmed advanced NSCLC with no prior systemic chemotherapy, PD-L1 positive (defined as PD-L1 TPS expression ≥1% [sp263]), and without EGFR, ALK or ROS1 genetic alteration if non-sq-NSCLC. Enrolled pts received 21-day cycles of S (250 mg orally QD) plus T (240 mg IV, Q3W) until disease progression or intolerable toxicity or the maximum duration of treatment with toripalimab is 24 months. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From July 2020 to September 2021, 55 pts were screened, of whom 23 pts were enrolled and received the treatment of S+T. Median age was 66 years (range: 49-73), 16 (69.6%) were male and 12 (52.2%) had squamous histology. Pts with PD-L1 TPS ≥50% and Conclusion: Surufatinib and toripalimab combination showed a promising antitumor activity in 1L therapy for advanced PD-L1 positive NSCLC with manageable toxicity. This study might represent a potential treatment option for these pts. Clinical trial information: NCT04169672. Citation Format: Ying Cheng, Lin Shen, Zhendong Chen, Feng Ye, Xianjun Yu, Xing Zhang, Dongmei Ji, Baorui Liu, Lijie Song, Chunjiao Wu, Ming Lu, Wei Chen, Jingxun Wu, Heli Gao, Desheng Weng, Weina Shen, Rutian Li, Minjie Yang, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su. Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT225.

e16199 Background: Patients with advanced neuroendocrine carcinoma (NEC) have a poor prognosis and limited treatment option after first-line treatment. Surufatinib, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1 and CSF-1R, has been approved in patients with advanced or metastatic extra-pancreatic neuroendocrine tumors in China. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Surufatinib modulates tumor immune microenvironment and has shown promising antitumor activity in combination with toripalimab in solid tumors, including neuroendocrine tumor and neuroendocrine carcinoma. Herein, we reported the efficacy and safety of surufatinib in combination with toripalimab in a cohort of advanced NEC patients. Methods: The multicenter, open-label, single-arm phase II clinical trial enrolled advanced NEC patients refractory to first-line chemotherapy, and received surufatinib 250 mg once a day orally plus toripalimab 240 mg intravenously on day 1 of a 21-day cycle. The primary end point is objective response rate (ORR) per RECIST 1.1. Results: Twenty-one patients enrolled and received combination therapy. At data cut-off (December 31, 2020), the average treatment cycles were 5.1±3.69 for surufatinib and 5.0±3.68 for toripalimab. Among 20 tumor evaluable patients, 4 patients achieved confirmed PR and 10 patients achieved stable disease. The ORR and disease control rate (DCR) are 20 % (95%CI: 5.7%-43.7%) and 70% (95%CI: 45.7%-88.1%) respectively. The median PFS is 3.94 months (95%CI: 1.31- unknown). OS is not mature till data cut-off. Adverse events (AEs) reported as related to treatment (TRAE) occurred in 100% of patients, of which Grade≥3 TRAEs occurred in 33.3% of patients. The reported Grade≥3 TRAEs were hypertension in 2 (9.5%) patients, and upper abdominal pain, oral mucositis, neutrophil count decreased, leukocyte count decreased, dermatitis, anemia and backache in 1 (4.8%) patient each. Immune related Grade ≥3 AEs, Gamma-glutamyl transpeptidase increased and dermatitis, occurred in 2 (9.5%) patients, respectively. TRAE caused surufatinib or toripalimab interruption occurred in 6 (28.6%) and 4 (19%) patients respectively. There were neither serious AEs nor AEs inducing treatment discontinuations or deaths. Conclusions: As there is no standard second-line treatment, this combination of surufatinib and toripalimab might offer a new promising choice to treat NEC as second-line treatment due to good efficacy and manageable treatment related toxicities. Clinical trial information: NCT04169672.

e16040 Background: Surufatinib is a novel small-molecule kinase inhibitor targeting VEGFRs, FGFR and CSF-1R, simultaneous targeting of angiogenesis through VEGFRs/FGFR1 and modulating tumor immune microenvironment through CSF-1R may be a uniquely potent strategy to enhance antitumor activity. Toripalimab is a monoclonal humanized IgG4 PD-1 antibody. Encouraging efficacy of surufatinib plus toripalimab treating patients with advanced solid tumors was reported at 2020 AACR. This is an ongoing, multicenter, open-label, single-arm, phase II study to evaluate the efficacy and safety of surufatinib in combination with toripalimab in various solid tumors. Here we report the results of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with histologically confirmed gastric or GEJ adenocarcinoma who have failed first-line of systemic chemotherapy were enrolled. Surufatinib 250 mg once a day (QD) will be orally administrated and toripalimab 240 mg will be intravenously administered every 3 weeks. Primary endpoint was the objective response rate (ORR) per RECIST v1.1. Results: As of Dec 31, 2020, a total of 21 gastric or GEJ adenocarcinoma patients were enrolled. The median age was 58 years old, and 81% of the patients were male. Median duration of treatment was 3 months (surufatinib, 3 months; toripalimab, 3 months). Among 15 patients with at least one post-baseline efficacy evaluation, 2 patients achieved confirmed partial response (PR), with 3 additional unconfirmed PR. And there were 6 in stable disease (SD), 3 in progressive disease (PD) and one not evaluable per RECIST v1.1. There were 5 in PR, 7 in SD and 2 in PD per irRECIST, respectively. The confirmed and unconfirmed ORR were 13.3% (95% CI: 1.7%-40.5%) and 33.3% (95% CI: 11.8%-61.6%), respectively. The disease control rate (DCR) was 73.3% (95% CI: 44.9%-92.2%) per RECIST v1.1. Median PFS was 3.71 months (95% CI: 1.41-unknown). 14.3% (3/21) of patients had treatment-related adverse events (TRAEs) of ≥ Grade 3. The most common TRAEs of ≥ Grade 3 were herpes zoster (4.8%), lymphopenia (4.8%), lymphocyte count decreased (4.8%), white blood cell count decreased (4.8%), liver injury (4.8%) and anaemia (4.8%). 4.8% (1/21) of patients had serious TRAEs. One patient died due to unknown reasons. Conclusions: Surufatinib plus toripalimab appeared to show encouraging activity in advanced gastric or GEJ adenocarcinoma with manageable safety profile. Such combination could be a promising strategy for advanced gastric or GEJ adenocarcinoma in the future. Clinical trial information: NCT04169672.

2514 Background: To explore the safety and synergistic anti-tumor effect of fruquintinib (a VEGFR inhibitor) in combination with sintilimab (an anti-PD-1 Ab) in patients (pts) with advanced colorectal cancer (CRC) and other solid tumors. Methods: This is an ongoing phase Ib/II, multicenter, two-stage study. Pts with variety cancer types, including CRC, were enrolled and is continuously enrolling in the study. For this interim analysis, all pts were analyzed for safety whereas only CRC pts were analyzed for efficacy. MMR status were analyzed for all enrolled CRC pts. Stage 1 was classical “3+3” dose escalation with pts assigned to one of the following 4 cohorts, fruquintinib taken orally at 3mg (Cohort A, 3 weeks on/ 1 week off), 4mg (Cohort B, 3 weeks on/ 1 week off), 5mg-intermittent (Cohort C, 2 weeks on/ 1 week off) or 3mg-continuous (Cohort E, once daily), while sintilimab was given at 200mg intravenously with Q4W in Cohort A and Cohort B whereas Q3W in Cohort C and Cohort E. DLT was observed for 28 days. Stage 2 was dose expansion with pts receiving 5mg-intermittent or 3mg-continuous fruquintinib plus sintilimab (200mg, Q3W). The primary endpoints were safety and tolerability and secondary endpoint was objective response rate (ORR). Results: As of Jan 5, 2021, 44 CRC pts which failed to at least 2 previous lines of therapy containing fluoropyrimidine, oxaliplatin or irinotecan were enrolled. They received either 5mg-intermittent or 3mg-continous dosage (n = 22, each), the ORR was 22.7% (10/44, 95% CI: 11.5-37.8%) with 27.3% (6/22, 95% CI: 10.7-50.2%) in 5mg-intermittent group and 18.2% (4/22, 95% CI: 5.2-40.3%) in 3mg-continuous group. With a median follow-up time of 8.3 (range: 0-9.6) months, the K-M estimated median PFS was 6.8 (95% CI:5.6-NA) months and 4.3 (95% CI:3.5-NA) months for 5mg-intermittent group and 3mg-continuous group, respectively. Overall, 60 pts were enrolled for safety analysis, including 23 in stage1 and 37 (only CRC) in stage 2. In stage 1, all pts experienced TEAEs, 52.2% of which were ≥ grade 3. The most frequently reported TEAEs were TSH increasing (73.9%), fecal occult blood positive (56.5%), and Palmar-plantar erythrodysaesthesia syndrome (PPES) (56.5%). SAEs occurred in 8 (34.8%) pts and no treatment-related death was reported. One patient in Cohort B reported manageable DLT. In stage 2, all pts experienced TEAEs, 18 (48.6%) pts experienced ≥ grade 3 TEAEs with 6 (31.6%) in 5mg-intermittent group and 12 (66.7%) in 3mg-continuous group. The most common TEAEs were proteinuria (45.9%) and TSH increasing (37.8%). TEAEs leading to either fruquintinib or sintilimab discontinuation occurred in 3 (5%) pts each. Conclusions: Fruquintinib plus sintilimab showed promising efficacy and favorable safety profile in advanced CRC. Clinical trial information: NCT03903705.