scholarly journals Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 trial (ORIENT-2)

2021 ◽  
Author(s):  
Jian Ming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Lei Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase

Abstract This randomized, open-label, multi-center phase 2 study (ClinicalTrials.gov, number NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemo in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line (1L) chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with treatment efficacy. The median OS in the sintilimab group was significantly prolonged compared with that of the chemotherapy group, (objective response rates 12.6% and 6.3 %, respectively). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1 %). Patients with high TCR clonality and low mTBI showed the longest median OS (15.0 mo), while patients with low NLR at 6 wk post-treatment had a significantly prolonged median OS compared with those with high NLR. High expression of T-follicular helper cells or activated B-cell signature was significantly associated with longer progression-free survival in the sintilimab group.

Sintilimab in patients with advanced esophageal squamous cell carcinoma refractory to previous chemotherapy: A randomized, open-label phase II trial (ORIENT-2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4511-4511 ◽  
Author(s):  
Jianming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Zhijun Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Phase 2 Trial ◽  
Line Chemotherapy

4511 Background: Patients (pts) with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line chemotherapy have limited treatment options. The study aims to evaluate the efficacy and safety of sintilimab, a PD-1 inhibitor, versus chemotherapy in these pts, and explore predictive value of PD-L1 and neutrophil-to-lymphocyte ratio (NLR) on efficacy of sintilimab. Methods: The open-label, multi-center phase 2 trial (NCT03116152) enrolled advanced ESCC pts refractory to first-line chemotherapy, and randomly assigned (1:1) them to receive sintilimab (200mg, Q3W) or chemotherapy (paclitaxel, 175mg/m2, Q3W; or irinotecan, 180mg/m2, Q2W), intravenously. The primary endpoint was overall survival (OS). Explorative endpoint were effects of PD-L1 and NLR on efficacy of sintilimab. Results: From May 16, 2017 to Aug 30, 2018, 190 pts were randomly assigned to sintilimab or chemotherapy (n = 95 per group). With the median follow-up of 7.2 months for sintilimab group and 6.2 months for chemotherapy group, the median OS in sintilimab was significantly higher than chemotherapy (7.2m vs. 6.2m, hazard ratio [HR] 0.70, P = 0.034). The objective response rate (ORR) was greater in sintilimab than chemotherapy with 12.6% vs. 6.3%, and the median duration of response was longer (8.3m vs. 6.2m). Incidences of treatment-related adverse events (TRAEs) of any grade (54.3% vs. 90.8%) and of grade 3-5 (20.2% vs. 39.1%) were both numerically less in sintilimab than in chemotherapy. The ORR in sintilimab versus chemotherapy in pts with tumor PD-L1 tumor proportion score (TPS) ≥1% and with TPS ≥10% were 20.2% vs. 0%, and 35.7% vs. 0%, respectively. In sintilimab group, pts with low NLR ( < 3) had a significant longer median OS (HR 0.54, P = 0.019) than with high NLR. Conclusions: Sintilimab was superior to chemotherapy with a significantly prolonged survival benefit and a favorable safety profile in pts with advanced ESCC refractory to first-line chemotherapy. High tumor PD-L1 expression (TPS ≥1% or ≥10%) might indicate more response benefit to sintilimab for these pts, and low NLR might be a positive predictive factor for sintilimab. Clinical trial information: NCT03116152 .

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

Sgnlva-005: Open-label, phase II study of ladiratuzumab vedotin (LV) for advanced aerodigestive tract malignancies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS469-TPS469
Author(s):  
Ian Churchill Anderson ◽  
Yinghui Wang ◽  
Zejing Wang ◽  
Rachel E. Sanborn
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Open Label ◽  
Open Label Phase

TPS469 Background: LIV-1 is a transmembrane protein with putative zinc transporter and metalloproteinase activity. It has been linked to the epidermal-to-mesenchymal transition that leads to malignant progression and metastasis. Ladiratuzumab vedotin (LV), also known as SGN-LIV1A, is an investigational antibody-drug conjugate (ADC) targeting LIV-1 that is composed of a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. MMAE-linked ADCs can induce mitotic arrest and immunogenic cell death. In a phase 1 study, LV was well tolerated and showed antitumor activity in heavily pretreated patients (pts) with metastatic breast cancer (Modi et al 2017). The current study was initiated to evaluate LV in previously treated pts with advanced upper aerodigestive tract malignancies. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy (2.5 mg/kg IV every 3 weeks) for pts with the following advanced malignancies: gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer (NSCLC)-squamous, NSCLC-nonsquamous, and head and neck squamous cell carcinoma. Up to approximately 30 pts with unresectable locally advanced or metastatic disease, measurable disease per RECIST v1.1, an ECOG score of 0 or 1, and adequate organ function are enrolling in each of the cohorts. Pts in the gastric and GEJ adenocarcinoma and esophageal squamous cell carcinoma cohorts must have received no more than 1 prior line of platinum-based cytotoxic chemotherapy and pts in the gastric and GEJ adenocarcinoma cohort should have received prior anti-PD(L)1 therapy if indicated. The study consists of a 2-stage design that includes a Bayesian predictive probability of success approach to determine futility criteria. Study objectives include objective response rate (primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study enrollment is ongoing in North America. Pts will also enroll in Europe and Asia. Clinical trial information: NCT04032704.

Retrospective study of nivolumab monotherapy for advanced esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 179-179
Author(s):  
Hayato Mikuni ◽  
Shun Yamamoto ◽  
Kotoe Oshima ◽  
Hidekazu Hirano ◽  
Natsuko Okita ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Treatment Rate ◽  
Practice Methods

179 Background: Based on the results of the ATTRACTION-1 and ATTRACTION-3 trials, nivolumab monotherapy has used for the treatment of metastatic or recurrence esophageal cancer patients who were refractory or intolerant to fluoropyrimidine and platinum since February 2020 in Japan. However, the ATTRACTION-1 trial mainly included patients who received nivolumab monotherapy as third or later-line treatments, which was different from the ATTRACTION-3 trial which mainly included patients as second-line treatment. Therefore, it is still unclear whether the treatment lines affect the efficacy of nivolumab in clinical practice. Methods: Medical records were retrospectively reviewed for patients diagnosed with metastatic or recurrence esophageal squamous cell carcinoma (ESCC) who received nivolumab monotherapy as second- or third or later-line treatments in our hospital. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) based on the RECIST ver1.1, and the incidences of adverse events (AEs) based on the CTCAE ver5.0. Results: Sixty-two patients were identified as the subject of this study. Thirty patients received nivolumab as second-line treatment (48.4%) and 32 patients as third or later-line treatments (51.6%). The median age (range) were 67 (33-80)/61 (52-84), PS 0 were 40.0/21.9%, prior taxane treatment rate were 6.7/93.8%, respectively. The ORR/DCR were 22.7/45.5% in second-line treatment, and 24.1/44.8% in third or later-line treatments (p=1.00). The median PFS (95% CI) was 2.3 (1.4-6.2)/2.3 (1.2-3.6) months in the second-/third or later-line treatments (HR=0.86, p=0.58). AEs of grade 3 or higher were observed in 6.7/6.3% of the second-/third or later-line treatments. Conclusions: There was no clear difference between second -line and third or later-line treatments in the short-term efficacy of nivolumab monotherapy in advanced ESCC patients.

Sign in / Sign up

Export Citation Format

Share Document