Sintilimab In Combination Research Articles

The Purpose of This Study is to Evaluate the Efficacy and Safety of Sintilimab in Combination With Xelox as Neoadjuvant Therapy for Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.

The Purpose of This Study is to Evaluate the Efficacy and Safety of Sintilimab in Combination With Xelox as Neoadjuvant Therapy for Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.

Abstract CT213: ORIENT-16: Sintilimab plus XELOX vs placebo plus XELOX as 1st line treatment for unresectable advanced gastric and GEJ adenocarcinoma

Abstract Background: Gastric cancer is one of the most common malignant tumors worldwide, and the 2nd most common in China. The development of new agents for the treatment of advanced gastric cancer is stagnant. Immunotherapy which inhibits the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) interaction is becoming a new option for treatment of late-stage gastric cancer (GC). Several trials suggest patients with PD-L1 positive expression (Combined Positive Score: CPS ≥ 1) population, especially CPS ≥ 10 population, are most likely to benefit from anti-PD-1 antibody treatment. Emerging data show encouraging efficacy signals of anti-PD-1 antibody in combination with chemotherapy in GC. Sintilimab, a highly selective, fully human, anti-PD-1 monoclonal antibody, was approved for relapsed or refractory Hodgkin Lymphoma in China in 2008. Based on the efficacy signals and the safety profile from a phase 1b trial of sintilimab plus XELOX regimen (oxaliplatin and capecitabine) as first line treatment for unresectable advanced gastric and GEJ adenocarcinoma, we aim to verify the therapeutic potential of sintilimab in combination with chemotherapy in patients with advanced GC/gastroesophageal junction (GEJ) cancer . Methods: The ORIENT-16 study (NCT: 03745170) is a randomized, double-blind, multi-center, phase III trial conducted in China to evaluate the efficacy and safety of sintilimab or placebo in combination with XELOX as first-line treatment in subjects with recurrent unresectable locally advanced or metastatic GC or GEJ adenocarcinoma. The study will enroll 650 patients. Patients will be randomly assigned in a 1:1 ratio to receive sintilimab every 3 weeks plus XELOX (capecitabine, 1000mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130mg/m2 intravenously on day1 every 3 weeks) or placebo plus XELOX for up to six cycles. Thereafter, the patients will receive maintenance therapy with sintilimab every 3 weeks plus capecitabine (1000mg/m2 orally twice daily for 14 days followed by 7 days off) or placebo plus capecitabine every 3 weeks. Sintilimab will be dosed according to the subject’s bodyweight ( < 60kg, 3mg/kg; ≥ 60kg, 200mg). Stratification factors are ECOG Performance status (0 or 1), liver metastasis (yes or no) and PD-L1 expression score in tumor cells and immune cells (DAKO 22C3: CPS < 10 or ≥ 10). Major eligibility criteria include age between 18 and 75 years; newly diagnosed, recurrent unresectable locally advanced or metastatic G or GEJ adenocarcinoma; at least one evaluable tumor lesion according to RECIST v1.1 criteria; and patients must have fresh tumor tissue or archival tumor tissue for PD-L1 assessment from within 6 months of entrance. Patients with known HER2 positive G or GEJ cancer are excluded. Treatment will be discontinued for disease progression, unacceptable toxicity, patient / physician decision to withdraw or after 24-months of treatment. The primary endpoint is median overall survival assessed in both entire population and in PD-L1 positive (CPS ≥ 10) population of patients. Secondary endpoints include progression free survival, objective response rate, disease control rate,duration of response and safety. Recruitment is currently ongoing in multiple sites in China. Citation Format: Jianming Xu, Yongshuai Jin, Ying Liu, Hui Zhou, Yan Wang. ORIENT-16: Sintilimab plus XELOX vs placebo plus XELOX as 1st line treatment for unresectable advanced gastric and GEJ adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT213.

Abstract CT211: ORIENT-15: A randomized, multicenter, double-blind, Phase III study of sintilimab + paclitaxel and cisplatin (TP) versus placebo + TP as first-line treatment in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma

Abstract Background: China has the largest population of patients with esophageal cancer in the world. The major histopathological type is squamous cell carcinoma and it accounts for more than 90% of the cases. About 40% esophageal squamous cell carcinoma (ESCC) are PD-L1 positive, however, the prognostic and predictive value of this biomarker remains elusive for this disease. Regardless of PD-L1 status, the median overall survival of patients with advanced or metastatic ESCC is about 10 months, reflecting an unmet medical need for new treatments. Sintilimab is a fully human anti-PD-1 monoclonal antibody that blocks the PD-1/PD-L1,PD-L2 interaction and restores T-cell response thereby destroying tumor cells. Sintilimab has a safety profile consistent with other approved PD-1 antibodies and was approved for relapsed/refractory Hodgkin lymphoma in China in 2018. Recently, comparing to chemotherapy, nivolumab and pembrolizumab significantly improved overall survival in second-line esophageal cancer patients, which suggests the application of PD-1 therapy in first-line ESCC. This randomized, multicenter, double-blind, Phase III study compares the efficacy and safety of sintilimab in combination with paclitaxel and cisplatin (TP) versus placebo with TP as first-line systemic treatment in patients with unresectable, locally advanced or metastatic ESCC in China. Methods: To be eligible, patients must be between 18 and 75 years of age, not eligible for definitive therapy, have untreated locally advanced recurrent or metastatic ESCC, have at least one measurable lesion, and must provide tumor tissue for PD-L1 assessment (tumor proportion score, TPS by Dako 22 C3) within 6 months prior to entrance. Patients with prior PD-1, PD-L1 or PD-L2 antibody treatment, cisplatin cumulative exposure ≥ 300 mg/m2, or esophageal or tracheal stent placement are excluded. A total of 640 subjects will be randomized in a 1:1 ratio to receive either sintilimab plus TP Q3W or placebo plus TP Q3W until unacceptable toxicity, disease progression, death or withdrawal of consent. Stratifying factors include PD-L1 TPS ≥ 10% or < 10%, liver metastasis or not, and ECOG PS 0 or 1. The primary endpoint is median overall survival assessed in the experimental and control groups in both the entire population and the PD-L1 positive (TPS ≥ 10%) population. The secondary endpoints are PFS, ORR, DCR, DoR and safety. Clinical trial information: NCT03748134. Citation Format: Lin Shen, Zhihao Lu, Linxinyu Xu, Yan Wang, Hui Zhou, Ying Liu. ORIENT-15: A randomized, multicenter, double-blind, Phase III study of sintilimab + paclitaxel and cisplatin (TP) versus placebo + TP as first-line treatment in patients with unresectable locally advanced or metastatic esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT211.

Sintilimab in Combination With Nab-paclitaxel in Patients With HNSCC (Head and Neck Squamous Cell Carcinoma )

Sintilimab in Combination With Nab-paclitaxel in Patients With HNSCC (Head and Neck Squamous Cell Carcinoma )

Efficacy and safety of sintilimab in combination with XELOX in first-line gastric or gastroesophageal junction carcinoma (GC/GEJC).

4042 Background: Immune checkpoint inhibitors have shown clinical benefit in advanced GC/GEJC. This phase 1b study evaluates the efficacy and safety of sintilimab, an anti-programmed cell death-1 antibody (PD-1 Ab) in combination with XELOX for GC/GEJC in first-line setting. Methods: This phase 1b study enrolled treatment-naïve unresectable locally advanced or metastatic GC/GEJC patients without HER2 amplification in cohort F. Patients received sintilimab 200mg IV q3w until disease progression, unacceptable toxicity or death, in combination with XELOX regimen (oxaliplatin 130mg/m2 IV D1 and capecitabine 1000mg/m2 PO BID D1-14) for up to 6 cycles. The primary objective was to evaluate the efficacy of the combination per RECIST v1.1 and safety and tolerability. Results: Totally 20 patients were enrolled in cohort F. As data cutoff (15 Jan 2019), median follow up was 5.8 months (range, 2.4 to 12.5). The median dose of sintilimab was 6.5 (range, 4 to 12). The objective response rate (ORR) was 85.0% (95%CI, 62.1 to 96.8) and disease control rate (DCR) was 100.0% (95%CI, 83.2 to 100.0). Among 17 patient with BOR of PR, two patients achieved a complete response (CR) of the target lesion. The median duration of response (DOR) and median progression free survival (PFS) had not been met. Three patients underwent resection of primary tumor after achieving a BOR of partial response (N=2) and stable disease (N=1). The incidence of treatment emergent adverse events (TEAEs) was 85.0%. Treatment-related AEs (TRAEs) occurred in 14 (70.0%) patients. The incidence of TRAE ≥ Grade 3 was 15%. AEs of immune-related etiology, occurred in 6 patients (30.0%). There were no AEs that resulted in death. As data cutoff, 12 patients were still in treatment and 8 had discontinued treatment and were under survival follow up. The biomarker analysis including PD-L1 expression in tumor specimen was ongoing. Conclusions: Sintilimab in combination with XELOX in first-line GC/GEJC shows promising anti-tumor efficacy and a tolerable safety profile. The further randomized, phase 3 study of Sintilimab in combination with XELOX in this setting is ongoing (NCT03745170). Clinical trial information: NCT02937116.

Phase Ib study of sintilimab in combination with chemotherapy for 1L advanced or metastatic non-small cell lung cancer (NSCLC).

e20546 Background: Anti-programmed death-1 antibodies (PD-1 Abs) have shown benefits in advanced NSCLC. The efficacy and safety of sintilimab, a PD-1 Ab, in combination with chemotherapy for 1L NSCLC is evaluated in this phase Ib study (NCT02937116). Methods: The study enrolled treatment-naïve unresectable locally advanced or metastatic non-squamous (nsq-) and squamous (sq-) NSCLC patients with neither EGFR mutations nor ALK rearrangements in cohort D and E respectively. Patients received sintilimab 200mg IV q3w in combination with pemetrexed 500mg/m2 and cisplatin 75mg/m2 IV q3w (4 cycles) in cohort D, or gemcitabine 1250mg/m2 D1,8 and cisplatin 75mg/m2 D1 IV q3W (6 cycles) in cohort E until disease progression, unacceptable toxicity or death. The primary objective was to evaluate the efficacy and safety of the combination. Results: As data cutoff (15 Jan 2019), 21 and 20 patients were enrolled in cohort D and E respectively. ORR in nsq- and sq-NSCLC were 68.4% (95%CI, 43.4 to 87.4) and 64.7% (95%CI, 38.3 to 85.8) respectively based on data of 19 and 17 patients with at least one radiological assessment. Median PFS was 11.4 months (95%CI, 3.1 to NA) and 6.5 months (95%CI, 5.3 to 8.0) respectively (Table). Totally 38 (92.7%) patients experienced at least one treatment emergent adverse event (TEAE). Treatment-related AEs (TRAEs) occurred in 28 (68.3%) patients. TRAE ≥grade 3 occurred in 4 (9.8%) patients. Immune related AEs occurred in 10 patients (24.4%), the most common of which were skin rash (N = 5), pneumonitis (N = 3) and hypothyroidism (N = 2). There was no AEs leading to death. The biomarker analysis was ongoing. Conclusions: The combination of sintilimab and chemotherapy showed efficacy with an acceptable safety profile in 1L nsq- and sq-NSCLC. Two phase III trials are ongoing to evaluate the combination in 1L nsq- (NCT03607539) and sq-NSCLC (NCT03629925) respectively. Clinical trial information: NCT02937116. [Table: see text]

Sintilimab in Combination With Chemotherapy in Neoadjuvant Treatment of Potentially Resectable Esophageal Cancer

Sintilimab in Combination With Chemotherapy in Neoadjuvant Treatment of Potentially Resectable Esophageal Cancer