scholarly journals Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e044696
Author(s):  
Nadine Ezard ◽  
Brendan Clifford ◽  
Adrian Dunlop ◽  
Raimondo Bruno ◽  
Andrew Carr ◽  
...  
Keyword(s):  
Adverse Events ◽  
Risk Behaviour ◽  
Phase 2 ◽  
Open Label ◽  
Dose Escalation Study ◽  
Stimulant Use ◽  
Treatment Services ◽  
Drug Tolerability ◽  
Methamphetamine Dependence ◽  
Icd 10

ObjectivesTo examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence.DesignA dose-escalating, phase-2, open-label, single-group study of oral LDX at two Australian drug treatment services.SettingThe study was conducted at two Australian stimulant use disorder treatment clinics.ParticipantsThere were 16 participants: at least 18 years old, MA dependent for at least the preceding 2 years using ICD-10 criteria, reporting use of MA on at least 14 of the preceding 28 days.InterventionsDaily, supervised LDX of 100–250 mg, single-blinded to dose, ascending-descending regimen over 8 weeks (100–250 mg over 4 weeks; followed by 4-week dose reduction regimen, 250–100 mg). Participants were followed through to week 12.OutcomesPrimary outcomes were safety, drug tolerability and regimen completion at the end of week 4. Participants were followed to week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence and neurocognitive functioning.ResultsFourteen of 16 participants (87.5%) completed escalation to 250 mg/day. Two participants withdrew from the trial in the first week: one relocated away from the study site, the other self-withdrew due to a possible, known side effect of LDX (agitation). There was one serious adverse event of suicidal ideation which resolved. All other adverse events were mild or moderate in severity and known side effects of LDX. No participant was withdrawn due to adverse events. MA use decreased from a median of 21 days (IQR: 16–23) to 13 days (IQR: 11–17) over the 4-week escalation period (p=0.013).ConclusionsLDX at a dose of up to 250 mg/day was safe and well tolerated by study participants, warranting larger trials as a pharmacotherapy for MA dependence.Trial registration numberACTRN12615000391572.

scholarly journals Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study

2020 ◽  
Author(s):  
Nadine Ezard ◽  
Brendan Clifford ◽  
Adrian Dunlop ◽  
Raimondo Bruno ◽  
Andrew Carr ◽  
...  
Keyword(s):  
Risk Behaviour ◽  
Phase 2 ◽  
Open Label ◽  
Dose Escalation Study ◽  
Duration Of Action ◽  
Treatment Services ◽  
Drug Tolerability ◽  
Methamphetamine Dependence ◽  
Global Health Issue ◽  
Clinical Trials Registry

Abstract Background: Methamphetamine (MA) dependence is a growing global health issue with no effective pharmacotherapy. Lisdexamfetamine (LDX) is approved for use in the treatment of attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder (BED) in doses ranging from 30 to 70mg/day. LDX has a longer duration of action and lower abuse potential than other amphetamines, and presents a promising candidate for agonist-type treatment of MA dependence. People seeking treatment for MA dependence may require doses of LDX higher than used in ADHD and BED. We examined the safety of LDX at 250mg/day among adults with MA dependence, approximately equivalent to previously trialled doses of dexamphetamine. Methods: We conducted a dose-escalating, phase-2, open label, single-group study of oral LDX at two Australian drug treatment services. Eligible participants were MA dependent adults who reported use of MA on at least 14 of the preceding 28 days. Once daily, supervised LDX doses of 100 to 250mg/day were provided as a single-blinded, ascending-descending dose regimen over 8 weeks. The primary outcomes were safety, drug tolerability, and regimen completion at the end of Week 4 (maximum dose). Participants were followed through to Week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence; and neurocognitive functioning. Results: Fourteen of 16 participants (87.5%) successfully completed the four week escalation regimen to 250mg/day. Two participants withdrew from the trial in the first week. No participant was withdrawn due to adverse events. MA use decreased significantly (p=0.013) from a median of 21 days (IQR: 16-23) to 13 days (IQR: 11-17) over the four week escalation period.Conclusions: LDX at a dose of up to 250 mg/day was safe and well tolerated in this population, with high retention. Larger trials of LDX as a pharmacotherapy for MA dependence are warranted. Trial Registration : Australian and New Zealand Clinical Trials Registry ACTRN12615000391572.

scholarly journals Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial

2021 ◽  
pp. 1-13
Author(s):  
Craig M. McDonald ◽  
Perry B. Shieh ◽  
Hoda Z. Abdel-Hamid ◽  
Anne M. Connolly ◽  
Emma Ciafaloni ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Natural History ◽  
Adverse Events ◽  
Exon Skipping ◽  
Control Group ◽  
Phase 2 ◽  
Open Label ◽  
M Phase ◽  
Positive Treatment

Background Eteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production. Objective To report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort. Methods Ambulatory patients aged 7–16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. An untreated cohort with DMD not amenable to exon 51 skipping was also enrolled. Results 78/79 eteplirsen-treated patients completed 96 weeks of treatment. 15/30 untreated patients completed the study; this cohort was considered an inappropriate control group because of genotype-driven differences in clinical trajectory. At Week 96, eteplirsen-treated patients showed increased exon skipping (18.7-fold) and dystrophin protein (7-fold) versus baseline. Post-hoc comparisons with patients from eteplirsen phase 2 studies (4658-201/202) and mutation-matched external natural history controls confirmed previous results, suggesting clinically notable attenuation of decline on the 6-minute walk test over 96 weeks (PROMOVI: –68.9 m; phase 2 studies: –67.3 m; external controls: –133.8 m) and significant attenuation of percent predicted forced vital capacity annual decline (PROMOVI: –3.3%, phase 2 studies: –2.2%, external controls: –6.0%; p <  0.001). Adverse events were generally mild to moderate and unrelated to eteplirsen. Most frequent treatment-related adverse events were headache and vomiting; none led to treatment discontinuation. Conclusions This large, multicenter study contributes to the growing body of evidence for eteplirsen, confirming a positive treatment effect, favorable safety profile, and slowing of disease progression versus natural history.

Efficacy and safety evaluation of HLX10 (a recombinant humanized anti-PD-1 monoclonal antibody) combined with albumin-bound paclitaxel in patients with advanced cervical cancer who have progressive disease or intolerable toxicity after first-line standard chemotherapy: A single-arm, open-label, phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17510-e17510
Author(s):  
Lingying Wu ◽  
Xiumin Li ◽  
Jing Wang ◽  
Lijing Zhu ◽  
Ruifang An ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Advanced Cervical Cancer ◽  
Phase 2 ◽  
First Line ◽  
Standard Chemotherapy ◽  
Open Label ◽  
Phase 2 Study ◽  
Line Standard

e17510 Background: Limited effective treatments are available for advanced cervical cancer patients who progress after first-line chemotherapy. Historic data indicate PD-1 antibodies have significant activity in advanced cervical cancer patients. This study was designed to determine the efficacy and safety of HLX10 (a recombinant humanized anti-PD-1 monoclonal antibody) plus albumin-bound paclitaxel in patients with advanced cervical cancer who have progressed on or are intolerant to first-line standard chemotherapy. Methods: This is an ongoing single-arm, open-label, multicenter, two-stage phase 2 study (NCT04150575). 143 eligible patients aged between 18 and 75, with histologically or cytologically diagnosed cervical cancer and positive PD-L1 expression (combined positive score [CPS] ≥1) were planned to be enrolled and given intravenous infusion of HLX10 (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every 3 weeks. Stage one (N = 20) was a safety run-in and preliminary efficacy exploration study with primary endpoints of adverse events, serious adverse events and objective response rate (ORR, assessed by IRRC per RECIST v1.1). In this stage, after all patients completed two tumor evaluations (every 6 weeks), a safety evaluation and a preliminary evaluation of anti-tumor efficacy were conducted to determine whether to proceed to the second stage (N = 123). Stage two is a single-arm, open-label, multicenter, phase 2 study with primary endpoint of ORR assessed by IRRC per RECIST v1.1. Results: Here we report the stage one results (safety and preliminary efficacy) of HLX10 in advanced cervical cancer patients. By cut-off date Oct 14, 2020, 21 eligible patients with median age of 50 (range: 31–65) and average CPS of 39.33 were enrolled; the median follow-up duration was 4.34 months. 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 52.4% (95% CI: 29.8%, 74.3%) and 42.9% (95% CI: 21.8%, 66.0%), respectively. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil counts (n = 7, 33.3%), decreased white blood cell count (n = 6, 28.6%) and anemia (n = 4, 19.0%). No TEAEs leading to drug discontinuation were observed. One death (multiple organ dysfunction syndrome) possibly related to treatment was reported. Conclusions: Stage one results demonstrated a manageable safety profile and encouraging efficacy (ORR 52.4%) of HLX10 plus albumin-bound paclitaxel in advanced cervical cancer patients who have progressive disease or intolerable toxicity to first-line standard chemotherapy, representing a novel potential treatment option that warranted further investigation. Clinical trial information: NCT04150575.

A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in Advanced Endometrial Cancer

2017 ◽  
Vol 27 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Patricia Pautier ◽  
Ignace Vergote ◽  
Florence Joly ◽  
Bohuslav Melichar ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Progression Free Survival ◽  
Megestrol Acetate ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Recurrent Endometrial Cancer

ObjectiveAdvanced/metastatic or recurrent endometrial cancer has a poor prognosis. Malignant endometrial tissue has high steroid sulphatase (STS) activity. The aim of this study was to evaluate STS as a therapeutic target in patients with endometrial cancer.MethodsThis was a phase 2, multicenter, international, open-label, randomized (1:1), 2-arm study of the STS inhibitor oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with advanced/metastatic or recurrent estrogen receptor–positive endometrial cancer. The primary end point was the proportion of patients without progression or death 6 months after start of treatment. Secondary end points included progression-free survival, time to progression, overall survival, and safety.ResultsSeventy-one patients were treated (36 with irosustat, 35 with megestrol acetate). The study was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of patients receiving irosustat or megestrol acetate had not progressed or died at 6 months, respectively. There were no statistically significant differences between irosustat and megestrol acetate in response and overall survival rates. Irosustat patients had a median progression-free survival of 16 weeks (90% confidence interval, 9.0–31.4) versus 40 weeks (90% confidence interval, 16.3–64.0) in megestrol acetate patients. Treatment-related adverse events occurred in 20 (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively. Most adverse events in both groups were grade 1 or 2.ConclusionsAlthough irosustat monotherapy did not attain a level of activity sufficient for further development in patients with advanced/recurrent endometrial cancer, this study confirms the activity of hormonal treatment (megestrol acetate) for this indication.

scholarly journals DOP60 Vedolizumab treatment persistence and safety in an extended access program (XAP)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S099-S100
Author(s):  
S Danese ◽  
K Subramanian ◽  
J Van Zyl ◽  
S Adsul ◽  
D Lindner ◽  
...  
Keyword(s):  
Data Analysis ◽  
Adverse Events ◽  
Dose Escalation ◽  
Open Label ◽  
Dose Escalation Study ◽  
Extended Access ◽  
Dosing Frequency ◽  
Access Program

Abstract Background Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis. Methods Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS. Results A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported. Conclusion High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.

scholarly journals A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti–PD-1 antibody, in patients with advanced solid tumors

2020 ◽  
Vol 8 (1) ◽  
pp. e000530 ◽  
Author(s):  
Aung Naing ◽  
Justin F Gainor ◽  
Hans Gelderblom ◽  
Patrick M Forde ◽  
Marcus O Butler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Phase 1 ◽  
Clinical Activity ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Dose Escalation Study ◽  
Wide Range ◽  
Tumor Types ◽  
Tumor Biopsies

BackgroundSpartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.MethodsIn the phase 1 part of the study, 58 patients received spartalizumab, intravenously, at doses of 1, 3, or 10 mg/kg, administered every 2 weeks (Q2W), or 3 or 5 mg/kg every 4 weeks (Q4W).ResultsPatients had a wide range of tumor types, most commonly sarcoma (28%) and metastatic renal cell carcinoma (10%); other tumor types were reported in ≤3 patients each. Most patients (93%) had received prior antineoplastic therapy (median three prior lines) and two-thirds of the population had tumor biopsies negative for PD-L1 expression at baseline. The maximum tolerated dose was not reached. The recommended phase 2 doses were selected as 400 mg Q4W or 300 mg Q3W. No dose-limiting toxicities were observed, and adverse events included those typical of other PD-1 antibodies. The most common treatment-related adverse events of any grade were fatigue (22%), diarrhea (17%), pruritus (14%), hypothyroidism (10%), and nausea (10%). Partial responses occurred in two patients (response rate 3.4%); one with atypical carcinoid tumor of the lung and one with anal cancer. Paired tumor biopsies from patients taken at baseline and on treatment suggested an on-treatment increase in CD8+ lymphocyte infiltration in patients with clinical benefit.ConclusionsSpartalizumab was well tolerated at all doses tested in patients with previously treated advanced solid tumors. On-treatment immune activation was seen in tumor biopsies; however, limited clinical activity was reported in this heavily pretreated, heterogeneous population. The phase 2 part of this study is ongoing in select tumor types.Trial registration numberNCT02404441.

scholarly journals Efficacy and safety of tolvaptan in patients with malignant ascites: a phase 2, multicenter, open-label, dose-escalation study

2020 ◽  
Author(s):  
Toshihiro Kudo ◽  
Yoshiyuki Murai ◽  
Yoshitsugu Kojima ◽  
Kenji Uehara ◽  
Taroh Satoh
Keyword(s):  
Body Weight ◽  
Ascitic Fluid ◽  
Dose Escalation ◽  
Urine Volume ◽  
Fluid Volume ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label ◽  
Dose Escalation Study ◽  
The Mean

Abstract Objective This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer. Methods In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75 mg/day, and the dose was increased daily to 7.5, 15 and 30 mg/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500 ml, at which point the patient proceeded to the maintenance phase of 5–7 days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume. Results The mean change from baseline in body weight was maintained below 0 kg throughout the study. The mean change (±standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45 ± 868.14 ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum: 1589.3 ml, minimum: 3.83 ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum: −2304.3 ml, minimum: −27.5 ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each). Conclusions Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75–30 mg/day.

Safety, tolerability, and pharmacokinetics (PK) of rilotumumab in Japanese patients (pts) with advanced solid tumors.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 130-130
Author(s):  
Toshihiko Doi ◽  
Rui Tang ◽  
Yilong Zhang ◽  
Elwyn Loh ◽  
Richard Lizambri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Solid Tumors ◽  
Phase 1 ◽  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Open Label ◽  
Eligibility Criteria ◽  
Dose Escalation Study

130 Background: Rilotumumab (R) is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor, the only known MET receptor ligand. The MET pathway has been identified as a potentially useful target for therapeutic blockade in oncology. R has been studied in multiple phase 2 trials either as monotherapy or combination therapy, including a phase 2 trial in gastric cancer combining R with epirubicin, cisplatin, and capecitabine. A phase 1 study was done to evaluate the safety, tolerability, and PK of R in Japanese pts. Methods: An open-label, dose-escalation study was performed with R at 10 mg/kg (Cohort 1A), escalating to 20 mg/kg (Cohort 1B) if no dose-limiting toxicities (DLTs) were observed. Key eligibility criteria were Japanese pts with unresectable locally advanced or metastatic carcinoma, age ≥ 20 yr, ECOG ≤ 1, and refractory to standard treatment (tx). Pts received R as an intravenous infusion on days 1 and 15 of each 28-day cycle, except for cycle 1 in which the day 15 dose was skipped to facilitate PK analysis. DLTs were evaluated in cycle 1. Results: A total of 9 pts were enrolled (1A, n = 3; 1B, n = 6). No DLTs were noted. As of 17 April 13, tx-emergent AEs were reported in 89% of pts. Tx-emergent AEs occurring in > 1 pt overall were vomiting (33%), diarrhea (22%), decreased hemoglobin (22%), hypoalbuminemia (22%), and nausea (22%). One grade 3 tx-emergent AE was observed (decreased hemoglobin; 10 mg/kg). Tx-related AEs were reported in 56% of pts. One grade ≥ 2 tx-related AE was observed (hypoalbuminemia; 20 mg/kg). 8 pts discontinued R due to disease progression; 1 pt remained on the investigational product. Mean exposure of R (Cmax and AUC) appeared to be doubled as dose increased from 10 to 20 mg/kg. The estimated mean CL was approximately 0.2 mL/hr/kg in both cohorts, suggesting a linear PK from 10 to 20 mg/kg. The terminal half-life of R was about 15 days. Conclusions: R monotherapy had an acceptable safety profile in Japanese pts with advanced solid tumors. These phase 1 safety and PK data support the further evaluation of R combined with chemotherapy in Japanese pts with MET-positive metastatic gastric cancer. Clinical trial information: NCT01791374.

Phase 2 study of zanubrutinib (BGB-3111) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7568-TPS7568
Author(s):  
Stephen Opat ◽  
Robert Marcus ◽  
Craig Anthony Portell ◽  
William Reed ◽  
Melannie Co ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Phase 1 ◽  
Critical Role ◽  
Safety Data ◽  
Drug Discontinuation ◽  
Phase 2 ◽  
Open Label ◽  
Serious Adverse Events ◽  
Major Hemorrhage

TPS7568 Background: Bruton tyrosine kinase (BTK) plays a critical role in B-cell receptor signaling, mediating B-cell proliferation, migration, adhesion and survival. BTK inhibition has emerged as a strategy for targeting B-cell malignancies, including MZL. In preclinical studies, zanubrutinib was shown to be a potent, irreversible, highly specific BTK inhibitor with excellent oral bio-availability and favorable pharmacokinetic/pharmacodynamic properties. Clinical data to date have shown that complete and sustained 24-hour BTK occupancy is associated with durable responses and suggested that zanubrutinib is generally well tolerated with low rates of serious adverse events. Preliminary results from the MZL cohort enrolled in the open-label, multicenter, phase 1 study demonstrated responses in 7 of 9 patients for an overall response rate (ORR) of 78%. Cumulative safety data also showed that zanubrutinib monotherapy was associated with infrequent incidence of atrial fibrillation and major hemorrhage and infrequent drug discontinuation due to treatment-related adverse events. This study is designed to evaluate the safety and efficacy of zanubrutinib in patients with R/R MZL. Methods: This ongoing global phase 2, single-arm, open-label study is examining zanubrutinib monotherapy in patients with R/R MZL who have received one or more prior lines of systemic therapy. Patients are treated with oral zanubrutinib at 160 mg twice-daily until progressive disease, unacceptable toxicity, or withdrawal of consent. Eligible patients must have histologically confirmed MZL, have received prior anti-CD20 antibody therapy, and have measurable disease. Disease response is assessed per the 2014 Lugano Classification for non-Hodgkin lymphoma. The primary endpoint is ORR determined by independent review committee (IRC). Key secondary endpoints include ORR by investigator assessment, time to and duration of response, time to treatment discontinuation, progression-free survival (all determined by IRC and investigator assessments), and overall survival and safety. Recruitment is ongoing.

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