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 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 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.

Approach and Feasibility of Patient-Reported Outcomes (PROs) in a Phase III Clinical Trial for Advanced Stage Classical Hodgkin Lymphoma (cHL) in Children and Adolescents

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3583-3583 ◽  
Author(s):  
Tara O Henderson ◽  
Sharon M Castellino ◽  
Frank G Keller ◽  
Kara M. Kelly ◽  
Rachael Curtis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Healthcare Utilization ◽  
Patient Reported Outcomes ◽  
Parent Report ◽  
Phase Iii ◽  
Classical Hodgkin Lymphoma ◽  
Patient Reported

Abstract Introduction: Given the high cure rates in classical Hodgkin lymphoma (cHL) with conventional therapy, careful consideration of the economics of newer agents should be considered. We describe the feasibility of embedding Patient-Reported Outcomes (PROs) for chemotherapy-induced peripheral neuropathy (CIPN) and cost effectiveness (CEA) in a randomized, multi-institutional Phase III study [NCT02166463; Children's Oncology Group (COG) AHOD1331], evaluating the efficacy of the novel agent, Brentuximab vedotin, for advanced cHL in children and adolescents. Methods: Recruitment for PROs of interest is targeted for 250 of the planned 600 trial participants. Participation in the trial includes prospective collection of patient- and parent proxy-reported outcomes. CIPN is evaluated with the 11-item FACT-GOG-NTX and paired with the 9-item CHRIs-Global to serially evaluate health-related quality of life (HRQL) consequences of CIPN from initial diagnosis to 12 months off therapy. For CEA, US-based participants are queried from diagnosis through 36 months off therapy with the 4-item Stanford Healthcare Utilization Questionnaire (parent-report), the Health Utilities Index (HUI) 2/3, and the 23-item Caregiver Work Limitations Questionnaire (parent-report) as a measure of productivity loss. A study-designated research assistant is charged with contacting site personnel at study entry and at each scheduled assessment. All data are uploaded into a web-based relational database for future analysis. Units of healthcare utilization from the Stanford Healthcare Utilization measure and adverse events (AE) requiring hospitalization will be monetized with unit costs from US-based administrative databases, including the US National Inpatient Sample (NIS) and Kids' Inpatient Database (KID), Massachusetts All-Payer Claims Database (APCD) and Medicare, based on site of care and diagnostic and/or procedure codes. Data on severe AE from the two predecessor trials (COG AHOD 0031 and AHOD 0831) will be monetized as a training exercise. Total costs will be calculated by study arm and will include monetization of significant adverse events and health care utilization and will be expressed as cost per quality-adjusted life year derived from the HUI. Results: The clinical trial, activated in March 2015, has enrolled 161 participants; accrual is ongoing at 172 participating institutions. 156 participants (>95%) have completed the baseline CIPN and CEA measures. Among participants who have completed the baseline CIPN and CEA assessments, 90% have completed subsequent measures. Monetization of significant adverse events and utilization is in progress. Conclusion: We demonstrate a feasible approach evidenced by high completion rates of assessments for prospective evaluation of CIPN, HRQL, and healthcare utilization in a multi-institutional trial of children with advanced HL. Our experience serves as a proof of principle to cooperative groups regarding the resources and the feasibility of incorporating necessary PRO and health utilization outcomes into Phase III clinical trials as a component of cancer care delivery research. Disclosures Henderson: Seattle Genetics: Research Funding.

Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therapy (UMIN ID: 000001704).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 499-499
Author(s):  
Takashi Iwata
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy ◽  
Pathological Response ◽  
Phase Ii Clinical Trial ◽  
Randomized Phase Ii

499 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Multicenter randomized phase II clinical trial of preoperative chemoradiotherapy by S-1 vs UFT for rectal cancer was conducted to compare the toxicity and efficacy of CRT using oral DPD-inhibitory fluoropyrimidines (UFT versus S-1, (UMIN ID: 000001704)) in patients with locally advanced rectal cancer. Methods: In this randomized phase II study, during April 2008 to October 2010, rectal cancer patients (n=59) who underwent preoperative CRT were randomly divided into two groups; S-1 group (n=30, 80 mg/m2/day, 5 days/w x 4 w), and UFT (n=29, 300 mg/m2/day, 5 days/w x 4 w). Both groups were combined with 40Gy radiotherapy (2 Gy ×5 days/w × 4 weeks,total 40 Gy). The pathological response rate, clinical response rate by RECIST, and frequency of adverse events of CRT were compared between S-1 group and UFT group. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60% (S-1) and 52% (UFT) (p=0.52). S-1 group showed 54% of response rate in pathological response, whereas UFT group showed 45% (p=0.43). In adverse events, frequence of Grade 2 and 3 diarrhea was significantly higher in S-1 group compared with UFT group. There was no difference between the two groups in compliance (S-1group: 83%, UFT group: 97%). Conclusions: Both S-1 and UFT were safely used for preoperative CRT. S-1 tended to show higher response rate than UFT, although diarrhea in S-1 was higher than in UFT. Clinical trial information: 000001704.

scholarly journals SAT-175 Trial in Progress Interim Report: A Phase II Clinical Trial Using Single Agent Cabozantinib in Advanced Adrenocortical Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sara Shokry Daniel Bedrose ◽  
Lina Altameemi ◽  
Marilyne Daher ◽  
Gina Tamsen De Rosa ◽  
Jeena Mary Varghese ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Adrenocortical Carcinoma ◽  
Hypertensive Crisis ◽  
Response To Therapy ◽  
Phase Ii Clinical Trial ◽  
Study Endpoint ◽  
Close Monitoring ◽  
Grade 3

Abstract BACKGROUND: Adrenocortical carcinoma (ACC) in an aggressive malignancy with suboptimal response to frontline chemotherapy and without established second line treatment. cMET activation is associated with ACC resistance to chemotherapy. Cabozantinib is a multi-kinase inhibitor that targets the VEGFR, c-MET, AXL, and RET receptors. We report interim data about using cabozantinib in ACC through a prospective phase II clinical trial. Methods: This is an investigator-initiated, open label clinical trial to evaluate the efficacy and safety of cabozantinib in patients with unresectable/metastatic ACC (ClinicalTrials.gov Identifier: NCT03370718). The primary objective is 4-month progression-free survival rate (PFS4). Participants are ≥ 18 years old with histologically confirmed ACC. Subjects who used mitotane within 6 months of consent must have mitotane serum level of < 2 mg/L. Cabozantinib starting dose is 60 mg daily with possible dose reductions. Subjects stopped treatment at time of disease progression, death, or occurrence of severe adverse events. Objective tumor responses were assessed per RECIST v.1.1 criteria. Adverse effects were graded per CTCAE v.4.03 Results: At time of data cut off (Oct 28, 2019), we screened 16 patients for enrollment. Ten patients (3 females) received cabozantinib out of whom 5 had history of mitotane use. Nine patients were eligible for response evaluation, defined as having at least one follow up imaging. One patient was taken off study after one week due to hypertensive crisis. Median age at time of diagnosis was 45 years (range 32 - 72). Five patients had hormonally active ACC. Median number of prior lines of systemic therapy was 2 (range 0 -5). Median duration of cabozantinib therapy was 6.6 months (range 0.7 -11.3). Eight patients (80%) were without evidence of progression at 4 months (achieved study endpoint). At time of data cut off, 1 patient had partial response (53% reduction over 8.8 months and ongoing), 3 patients had stable disease, and 5 patients had progressive disease. Nine patients were alive with disease and one patient died (not drug related). Grade 3/4 clinical adverse events included thromboembolic events (3 patients), severe hypertension (1 patient), intracranial hemorrhage secondary to hypertensive crisis (1 patient), weight loss (1 patient), and abdominal pain (1 patient). Grade 3/4 laboratory adverse events included increased AST (2 patient), increased ALT (1 patient), increased GGT, increased amylase (1 patient), increased lipase (1 patient) and hyponatremia (1 patient). Conclusions: In this interim analysis of phase II study, majority of subjects reached the study primary endpoint (PFS4). These data are in favor of continuing study accrual to assess magnitude of response to therapy and safety profile in ACC. Aggressive blood pressure management and close monitoring of liver enzymes are crucial to ensure the safety of study subjects.

scholarly journals Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial

2021 ◽  
Author(s):  
Pauline Byakika-Kibwika ◽  
Christine Sekaggya-Wiltshire ◽  
Jerome Roy Semakula ◽  
Jane Nakibuuka ◽  
Joseph Musaazi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Viral Load ◽  
Adverse Events ◽  
Phase Ii ◽  
Intervention Group ◽  
Viral Clearance ◽  
Phase Ii Clinical Trial ◽  
Control Group ◽  
Open Label ◽  
Open Label Phase

Abstract BackgroundSeveral repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DesignWe conducted a randomized open label Phase II clinical trial from October -December 2020.MethodsPatients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6.ResultsOf the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p=0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group.ConclusionOur results show that HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution. Trial registration: NCT04860284

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