scholarly journals Gls-010, a Novel Anti-PD-1 Mab in Chinese Patients with Relapsed or Refractory Classical Hodgkin Lymphoma: Preliminary Impressive Results of a Phase II Clinical Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-17
Author(s):  
Yuqin Song ◽  
Jun Zhu ◽  
Ningjing Lin ◽  
Mingzhi Zhang ◽  
Hai Bai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Objective Response ◽  
Genetic Alterations ◽  
Phase Ii Clinical Trial ◽  
Chinese Patients ◽  
Classical Hodgkin Lymphoma ◽  
Effective Treatment Option

Introduction: Classical Hodgkin lymphoma (cHL) is characterized by genetic alterations in 9p24.1, leading to overexpression of PD-L1 ligand. GLS-010 is a novel fully human anti-PD-1 monoclonal antibody (mAb) and exhibited favorable results in previous Phase I study. The aim of this study was to evaluate the safety and efficacy profile of GLS-010 in Chinese patients (pts) with relapsed or refractory cHL. Methods: In this multi-center, single-arm Phase II clinical trial, pts with relapsed or refractory cHL after at least 2 lines of prior systemic chemotherapies were enrolled and treated with GLS-010 240mg every 2 weeks until disease progression, death, unacceptable toxicity or withdraw from the study. Efficacy was assessed with the primary endpoint of objective response rate (ORR) by independent review committee (IRC) per Lugano 2014. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: As of April 18, 2020, a total of 85 pts with relapsed or refractory cHL received a median of 14.5 treatment cycles (1 cycle include 2 injections). The pretreatment characteristics of the pts are shown in Table 1. At a median follow-up of 15.8 months, 28.2% (24/85) of pts discontinued treatment. As shown in Table 2, treatment-related adverse events (TRAEs) of any grade occurred in 79 (92.9%) of 85 patients, most of which were Grade 1-2. The most common TRAEs were fever (27/85, 31.8%), neutrophil count decreased (17/85, 20%) and alanine aminotransferase (ALT) increased (17/85, 20%). Grade ≥3 TRAEs occurred in 25 (29.4%) pts, most commonly, hepatic function abnormal (5/85, 5.88%) and hyperuricaemia (4/85, 4.71%). For all the 85 pts, ORR was 90.59% (77/85, 95%CI: 82.30-95.85) with 32.9% (28/85) of patients achieving a CR and 57.6% (49/85) of patients achieving a PR (Table 3). Median duration of response (DoR) and progression free survival (PFS) were not reached yet. Conclusions: GLS-010 showed impressive anti-tumor activity (ORR=90.59%) and manageable safety profile in Chinese patients with relapsed or refractory cHL, and could be a new safe and effective treatment option. Disclosures Meng: Guangzhou Gloria Biosciences Co., Ltd.: Current Employment.

Gls-010, a novel anti-PD-1 mAb in Chinese patients with relapsed or refractory classical Hodgkin lymphoma: Preliminary impressive result of a phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8033-8033
Author(s):  
Yuqin Song ◽  
Jun Zhu ◽  
Ningjing Lin ◽  
Mingzhi Zhang ◽  
Hai Bai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Genetic Alterations ◽  
Phase Ii Clinical Trial ◽  
Chinese Patients ◽  
Favorable Result ◽  
Classical Hodgkin Lymphoma ◽  
Impressive Result

8033 Background: classical Hodgkin lymphoma (cHL) are characterized by genetic alterations at the 9p24·1 locus and PD-L1 ligand overexpression. GLS-010 is a novel fully human anti-PD-1 mAb and exhibited favorable result in previous Phase I study. This multi-center, single-arm Phase II clinical trial is aimed to further evaluate the safety and efficacy profile of GLS-010 in Chinese patients (pts) with relapsed or refractory cHL. Methods: All pts enrolled received GLS-010 240mg every 2 weeks until disease progression, death, unacceptable toxicity or withdraw from the study. The primary endpoint was objective response rate (ORR) by independent review committee (IRC) per Lugona 2014. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: 85 pts with relapsed or refractory cHL who had received at least 2 lines of prior systemic chemotherapies were enrolled and treated. As of August 2 2019, data cutoff, pts received a median of 8 treatment cycles (1 cycle include 2 injections), with 12 pts discontinued and 73 pts were still in treatment. At a median follow-up of 6.57 months, an ORR was reported in 78 of 85 patients (91.76%, 95%CI, 83.77-96.62), by an IRC assessment, including 30(35.3%) pts with a complete response (CR) and 48 pts (56.5%) with a partial response (PR). Median duration of response (DoR) and progression free survival (PFS) were not reached yet. Treatment-related adverse events (TRAEs) of any grade occurred in 77 (90.6%) of 85 patients, most of which were Grade 1-2.The most common TRAEs were fever (26/85, 30.6%), neutrophil count decreased (16/85, 18.82%), white blood cell count decreased (15/85, 17.65%). ≥ Grade 3 TRAEs occurred in 23 (27.06%) pts, most commonly, hepatic function abnormal (5/85, 5.88%), hyperuricaemia (4/85, 4.71%). Conclusions: GLS-010 showed impressive anti-tumor activity (ORR = 91.96%) and manageable safety profile in Chinese patients with relapsed or refractory cHL, which could be a new safe and effective treatment option in this setting. Clinical trial information: NCT03655483 .

scholarly journals Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2307 ◽  
Author(s):  
Camilo Jimenez ◽  
Vivek Subbiah ◽  
Bettzy Stephen ◽  
Junsheng Ma ◽  
Denai Milton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Primary Tumor ◽  
Objective Response ◽  
Inflammatory Cells ◽  
Phase Ii Clinical Trial ◽  
Survival Duration

Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare endocrine malignancies that are associated with high rates of morbidity and mortality because of their large tumor burden and location, progression, and release of catecholamines. Systemic therapies for MPPGs are limited. MPPGs are characterized by pseudohypoxia that may prevent immune system recognition. We conducted a phase II clinical trial of pembrolizumab in patients with progressive MPPGs. The primary endpoint was the non-progression rate at 27 weeks. The secondary endpoints included the objective response and clinical benefit rates, progression free and overall survival duration, and safety. We also determined whether PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor were associated with clinical response and hereditary background. Eleven patients were included in this trial, four (36%) with germline mutations and seven (64%) with hormonally active tumors. Four patients (40%, 95% confidence interval (CI) 12–74%) achieved the primary endpoint. The objective response rate was 9% (95% CI: 0–41%). The clinical benefit rate was 73% (95% CI: 39–94%). Four patients had grade 3 adverse events related to pembrolizumab. No patients experienced grade 4 or 5 adverse events or a catecholamine crisis. Progression free survival time was 5.7 months (95% CI: 4.37—not reached). The median survival duration was 19 months (95% CI: 9.9—not reached). PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor did not seem to be associated with disease response. Single-agent pembrolizumab has modest treatment efficacy in patients with progressive MPPGs. Positive responses seemed to be independent of patients’ hereditary backgrounds, tumor hormonal status, and the presence of infiltrating mononuclear inflammatory cells or PDL-1 expression in the primary tumor.

Dual immune checkpoint blockade in advanced well-differentiated neuroendocrine tumors, a phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16201-e16201
Author(s):  
Susan Combs Scott ◽  
Ana De Jesus-Acosta ◽  
Chen Hu ◽  
Benjamin Philip Levy ◽  
Valsamo Anagnostou ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Median Duration ◽  
Primary Endpoint ◽  
Response Rate ◽  
Objective Response ◽  
Phase Ii Clinical Trial ◽  
Open Label ◽  
Well Differentiated

e16201 Background: Limited systemic treatment options are available for progressive well-differentiated neuroendocrine tumors (NET), also called carcinoid tumors. Given emerging evidence for immunotherapy response in high grade NET including small cell lung cancer, we sought to determine the efficacy of combination immunotherapy with ipilimumab and nivolumab in patients with advanced, progressive, well-differentiated NET in an open label phase II clinical trial. Methods: Eligible patients had well-differentiated, nonfunctional NET of lung, pancreas, or GI origin that had progressed within the past 12 months after at least one line of prior therapy. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1mg/kg every 6 weeks for up to 2 years. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Using a Simon’s 2-stage design, the study planned to accrue up to 56 patients. Based on published response rates to everolimus of 5%, we hypothesized that this regimen would be considered promising if the true ORR is > 15%. Results: Nine patients were enrolled prior to study closure due to funding, including 6 patients with NET of lung origin, 2 pancreatic, and 1 small bowel (Table). Median age was 71 years. All patients had distant metastatic disease at enrollment, with an average of 2 prior lines of therapy. Four of 9 patients achieved the primary endpoint of confirmed objective response, all of whom have ongoing response with a median duration of 15.4 months. Five of 9 patients, including all 4 responders, experienced immune-related toxicity requiring treatment modification or discontinuation. The trial did not accrue the target of 56 patients, however, objective response in 4 of 9 patients (ORR 44.4%, 90% CI: 16.9-74.9%) excluded the response rate target (15%). Conclusions: The impressive ORR of 44% with a median duration of response exceeding 15 months in this small clinical trial warrants further study of combination CTLA-4 and PD-1 inhibition in previously treated well-differentiated NET. Our ongoing immunologic and genomic correlative analysis in responders and non-responders will help inform future study of immunotherapy in this patient population in need of new systemic therapy approaches. Clinical trial information: NCT03420521. [Table: see text]

Gls-010, a novel anti-PD-1 mAb in Chinese patients with recurrent or metastatic cervical cancer: Results from a multicenter, open-label and single-arm phase II trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6032-6032
Author(s):  
Xiaohua Wu ◽  
Lingfang Xia ◽  
Qi Zhou ◽  
Jianqing Zhu ◽  
Ke Wang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cervical Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Chinese Patients ◽  
Current Evidence ◽  
Fixed Dose ◽  
Favorable Result ◽  
Open Label ◽  
Duration Of Response

6032 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase I study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase II Dose (RP2D). This Phase II clinical trial is aimed to further evaluate the safety and anti-tumor activity of GLS-010 in patients with recurrent or metastatic cervical cancer. Methods: PD-L1 positive (combined positive score (CPS) ≥1) patients with recurrent or metastatic cervical cancer who had received one or more lines of chemotherapy were enrolled and received GLS-010 240mg every 2 weeks. Primary endpoint was the objective response rate (ORR) per RECIST 1.1, secondary endpoints included duration of response (DoR) and safety. Results: From May 16th 2019 to December 24th 2019, 44 pts were enrolled and treated in the study. As of December 24th 2019,the median line of prior systemic chemotherapy was 2(range: 1~4), and 59% (26/44) of pts had received ≥2 previous lines of chemotherapy. The median number of GLS-010 doses was 1.5(range: 1~4). 25 pts received response evaluation per investigator review. With a median follow-up of 2.9 months, 7 of 25 evaluable pts achieved a partial response (PR). The ORR was 28% (95% CI, 12.07-49.39), with 7 pts achieving a PR ( 3 of 7 confirmed), 3 pts achieving stable disease (SD) and 15 pts with progressive disease (PD), 1 of which was assessed as dissociated response with treatment ongoing. Median duration of response had not been reached yet. 33 of 44 patients (75%) experienced one or more treatment-related adverse events (TRAEs) per NCI CTCAE v4.03, most of which were grade 1 or 2. The most common TRAEs were Anaemia (15/44), and 73.3% of them were grade 1 or 2. The most common ≥grade 3 TRAE included Anaemia (4/44). As data cut off, only 1 pt discontinued treatment due to adverse event. Conclusions: GLS-010 showed impressive therapeutic activity and manageable safety profile in Chinese recurrent or metastatic cervical cancer patients. Current evidence support further development of GLS-010 in this and more indications. This trial is still ongoing, and we are looking forward to further results. Clinical trial information: NCT03972722.

Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with unresectable hepatocellular carcinoma (HAIROX): A phase II, single-arm, prospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4574-4574
Author(s):  
Shiguang Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Objective Response ◽  
Hepatic Arterial Infusion ◽  
Arterial Infusion ◽  
Intention To Treat ◽  
Unresectable Hepatocellular Carcinoma ◽  
Treat Population

4574 Background: Chemoembolisation and oral sorafenib are the recommended treatment for unresectable hepatocellular carcinoma (HCC); however, some patients respond poorly to these. Hepatic arterial infusion (HAI) chemotherapy may have potential benefit in these patients. We aimed to investigate the efficacy and safety of HAI of oxaliplatin plus raltitrexed in patients with unresectable HCC. Methods: In this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with unresectable HCC at the Fujian Cancer Hospital (China). We performed HAI with oxaliplatin (100 mg/m2 for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon’s two-stage design. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade 4 adverse events or deaths were not reported, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusions: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients unresectable HCC, and further evaluation is warranted. Clinical trial information: ChiCTR-OOC-17014182 . [Table: see text]

scholarly journals Nivolumab for the Treatment of Classical Hodgkin Lymphoma

2017 ◽  
Vol 33 (6) ◽  
pp. 237-244
Author(s):  
Maryann R. Cooper ◽  
Bassem Almalki ◽  
Kristine C. Willett
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Objective Response ◽  
Immune Surveillance ◽  
Progression Free Survival ◽  
Classical Hodgkin Lymphoma ◽  
Durable Response

Objective: To review nivolumab for the treatment of classical Hodgkin lymphoma (cHL). Data Sources: Literature searches were conducted in Medline (1946 to May week 3 2017), EMBASE (1974 to 2017 week 22), and Google Scholar using the terms Hodgkin lymphoma AND nivolumab. Study Selection and Data Extraction: Two clinical trials (phase I and phase II) were identified. Data Synthesis: Nivolumab inhibits programmed death receptor-1 allowing for increased T-cell mediated immune surveillance of tumors. Nivolumab was evaluated in cHL patients after failure of autologous stem cell transplantation and brentuximab vedotin consolidation. Patients received nivolumab 3 mg/kg every 2 weeks. In the phase I trial, the objective response rate was 87% (95% confidence interval [CI] = 66-97) and the rate of progression-free survival (PFS) at 24 weeks was 86% (95% CI = 62-95). The most common adverse events (AE) included rash (22%) and decreased platelet count (17%). Following extended follow-up at a median of 86 weeks, 50% of the initial responders maintained a durable response. In the phase II clinical trial, 53 patients (66.3%, 95% CI = 54.8-76.4) achieved an objective response and PFS at 6 months was 76.9% (95% CI = 64.9-85.3). The common AE were fatigue (25%), infusion-related reactions (20%), and rash (16%). After further follow-up at a median of 15.4 months, 12-month overall survival was 94.9% (median overall survival not reached). Conclusions: Nivolumab is an effective option in treating patients with relapsed/refractory cHL with an acceptable safety profile. Further studies are needed to investigate the role of nivolumab for the treatment of cHL.

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