scholarly journals Efficacy and safety results from CheckMate 140, a phase 2 study of nivolumab for relapsed/refractory follicular lymphoma

Blood ◽  
2020 ◽  
Author(s):  
Philippe Armand ◽  
Ann MH Janssens ◽  
Giuseppe Gritti ◽  
John Radford ◽  
John M Timmerman ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Tumor Associated Macrophage ◽  
Phase 2 Trial ◽  
Programmed Death ◽  
Phase 2 Study ◽  
Programmed Death 1

Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to evaluate further its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least two prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary endpoint was objective response rate (ORR) assessed by independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4/92). Median PFS was 2.2 months (95% confidence interval [CI], 1.9-3.6). Median DOR was 11 months (95% CI, 8-14). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than non-responders, but no significant differences in PD-1 or PD-L1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.

scholarly journals Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

Haematologica ◽  
2016 ◽  
Vol 102 (4) ◽  
pp. e156-e159 ◽  
Author(s):  
Gilles Salles ◽  
Stephen J. Schuster ◽  
Sven de Vos ◽  
Nina D. Wagner-Johnston ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Subgroup Analysis ◽  
Alkylating Agent ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 2 Study

Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3947-3952 ◽  
Author(s):  
Lionel Adès ◽  
Simone Boehrer ◽  
Thomas Prebet ◽  
Odile Beyne-Rauzy ◽  
Laurence Legros ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Potential Role ◽  
Cytogenetic Response ◽  
International Prognostic Scoring System ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 2 Trial ◽  
Phase 2 Study ◽  
Rbc Transfusion

AbstractHigher-risk MDS with del5q carry a poor prognosis. In this phase 2 trial, 47 patients with higher-risk MDS received lenalidomide 10 mg/day. International Prognostic Scoring System was high in 60%, intermediate-2 risk in 40%. del 5q was isolated, with one additional and more than one additional abnormality in 19%, 23%, and 58% patients, respectively. Thirteen (27%) patients achieved hematologic response, including 7 hematologic complete remission (CR) (with complete [4] or partial [3] cytogenetic response), 2 marrow CR and 4 hematologic improvement erythroid, and 12 became red blood cell (RBC) transfusion independent, for a median duration of 6.5 months. Median CR duration was 11.5 months. Six of 9 (67%) patients with isolated del 5q achieved CR, versus 1 of 11 and none of 27 patients with one or more than one additional abnormality, respectively (P < .001). Seven of 20 (35%) with initial platelets more than 100 000/mm3 obtained CR, compared with none of the 27 with lower platelet counts less than 100 000/mm3 (P = .001). Our data support a potential role of lenalidomide in higher-risk MDS with isolated del 5q. This trial was registered at www.clinicaltrials.gov as NCT00424229.

scholarly journals Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuankai Shi ◽  
Jianqiu Wu ◽  
Zhen Wang ◽  
Liling Zhang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Peripheral T Cell Lymphoma ◽  
Serious Adverse Events ◽  
Phase 2 Study

Abstract Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

A Phase 2, Open-Label, Multicenter Study of Tazemetostat in Combination with Rituximab for the Treatment of Relapsed or Refractory Follicular Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4 ◽  
Author(s):  
Krish Patel ◽  
Neil Bailey ◽  
John M. Pagel
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Multicenter Study ◽  
Systemic Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label

Background: Patients with follicular lymphoma (FL) who do not achieve a response after 2 or more prior lines of systemic therapy have a poor prognosis when treated with salvage chemotherapy alone or PI3K inhibitors. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that supports germinal center (GC) formation and suspends differentiation during B-cell development by silencing genes that limit proliferation and promote exit from the GC. Throughout the pathogenesis of FL, EZH2 plays a consistent underlying role in maintaining the GC and B-cell proliferation, regardless of the oncogenic drivers. Dysregulation of EZH2 or gain-of-function mutations in EZH2 can lead to accumulation of malignant B cells and may contribute to the development of FL. Tazemetostat, a first-in-class oral EZH2 inhibitor, recently gained approval by the US Food and Drug Administration in patients with relapsed or refractory (R/R) FL after demonstrating single-agent, antitumor activity in patients with mutant (MT) or wild-type (WT) EZH2 R/R FL. Here we examine the efficacy and safety of tazemetostat in combination with rituximab for the treatment of R/R FL. Study Design and Methods: This trial is a phase 2, single-arm, open-label, multicenter study of tazemetostat in combination with rituximab in patients with R/R FL who have received at least 2 prior lines of systemic therapy, including an anti-CD20-based regimen. Patients eligible for inclusion are aged ≥18 years with grade 1 to 3A FL who have met Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria to receive treatment, have an Eastern Cooperative Oncology Group (ECOG) score ≤2, have &gt;5.0 x 109/L circulating malignant cells, and have not received any prior treatment with EZH2 inhibitors. Patients with transformed FL, a history of clinically significant gastrointestinal conditions, or any uncontrolled illness are excluded from this study. EZH2 mutation testing will be performed during patient screening. Patients will receive tazemetostat 800 mg by mouth twice daily beginning on cycle 1 day 1 for continuous 28-day cycles until the end of cycle 24, for a total of 24 months of therapy. Patients will also receive rituximab 375 mg/m2 intravenously (IV) on cycle 1 day 1, then 375 mg/m2 IV or 1400 mg subcutaneously on days 8, 15, and 22 of cycle 1, and on day 1 of cycles 3, 4, 5, and 6, for a total of 8 doses of rituximab. The primary endpoint is the objective response rate (ORR; the proportion of patients with complete or partial response) in patients with WT EZH2. Key secondary endpoints include median progression free survival (PFS) in patients with WT EZH2; median PFS in all patients, regardless of mutational status; ORR in patients with MT EZH2; efficacy outcomes in rituximab-refractory patients; and incidence of adverse events. Efficacy and safety analyses will be performed on all patients who receive ≥1 dose of study drug. The evaluation of ORR will be based on Lugano 2014 response criteria and will be presented with corresponding 2-sided Clopper-Pearson 95% confidence intervals. The Kaplan-Meier method will be used to estimate PFS. Survival follow-up will be done following the study treatment period every 6 months for 2 years or until disease progression or death for all patients who complete the 24 months of tazemetostat therapy. Disclosures Patel: Adaptive Biotechnologies, AstraZeneca, Pharmacyclics, Janssen, Genentech, Celgene/BMS, BeiGene, Kite: Consultancy. Pagel:Gilead, Pharmacyclics LLC, an AbbVie Company, and AstraZeneca: Consultancy.

Idelalisib efficacy and safety in follicular lymphoma patients from a phase 2 study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 8529-8529
Author(s):  
Gilles A. Salles ◽  
Stephen J Schuster ◽  
Sven De Vos ◽  
Nina D. Wagner-Johnston ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 2 Study

scholarly journals ELARA: A PHASE 2 TRIAL INVESTIGATING THE EFFICACY AND SAFETY OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH REFRACTORY/RELAPSED FOLLICULAR LYMPHOMA

2019 ◽  
Vol 37 ◽  
pp. 559-560
Author(s):  
M. Dickinson ◽  
L. Popplewell ◽  
A. Kolstad ◽  
P.J. Ho ◽  
T. Teshima ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Adult Patients ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 2 Trial

Phase 2 study of programmed death-1 antibody (anti-PD-1, MK-3475) in patients with microsatellite unstable (MSI) tumors.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS3128-TPS3128 ◽  
Author(s):  
Dung T. Le ◽  
Nilofer Saba Azad ◽  
Dan Laheru ◽  
Ilene S. Browner ◽  
Hao Wang ◽  
...  
Keyword(s):  
Phase 2 ◽  
Programmed Death ◽  
Phase 2 Study ◽  
Programmed Death 1

Brigatinib (BRG) in crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): Updates from ALTA, a pivotal randomized phase 2 trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20503-e20503 ◽  
Author(s):  
Myung-Ju Ahn ◽  
D. Ross Camidge ◽  
Marcello Tiseo ◽  
Karen L. Reckamp ◽  
Karin Holmskov Hansen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase 1 ◽  
Objective Response ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Best Response ◽  
Grade 3 ◽  
Nsclc Patients ◽  
To Receive ◽  
Randomized Phase 2

e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text]

scholarly journals Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Huijie Bian ◽  
Zhao-Hui Zheng ◽  
Ding Wei ◽  
Aidong Wen ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Lung Tissue ◽  
Phase 1 ◽  
Area Under The Curve ◽  
Blood Pool ◽  
Control Group ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Phase 2 Study

AbstractsRecent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

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