First-in class selective AXL inhibitor bemcentinib (BGB324) in combination with LDAC or decitabine exerts anti-leukaemic activity in AML patients unfit for intensive chemotherapy: Phase II open-label study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7043-7043 ◽  
Author(s):  
Sonja Loges ◽  
Michael Heuser ◽  
Jörg Chromik ◽  
Carlos Enrique Vigil ◽  
Peter Paschka ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Negative Regulator ◽  
Second Phase ◽  
Intensive Chemotherapy ◽  
Open Label ◽  
Open Label Study ◽  
Tumour Immunity ◽  
De Novo Aml ◽  
Grade 3

7043 Background: The RTK AXL represents a therapeutic target promoting AML cell proliferation and survival by pleiotropic mechanisms and is a negative regulator of anti-tumour immunity. Bemcentinib is a first-in-class, highly selective, oral AXL inhibitor that has previously shown encouraging anti-leukaemic activity as a monotherapy in r/r AML and hr-MDS. Methods: A monotherapy dose-escalation and expansion part of this trial is complete. In this second, phase II part of the study, 11 and 15 AML pts unfit for intensive chemotherapy received bemcentinib at RP2D (200 mg po/d) in combination with low-dose cytarabine (LDAC) and decitabine, respectively. Median age was 77 yr (range: 50-83), median screen myeloblast count 39% (3-95%) and 2/19 (11%) of pts evaluable for FLT3 were FLT3+. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at screen and following treatment. Results: The most common TRAEs (≥ 15% of pts) were ECG QT prolongation (35%) and diarrhoea (15%). Among these, 3 were Grade 3, and none 4 or 5. All TRAEs were manageable and/or reversible. As of Feb ‘19, 9 pts (2 de novo, 1 secondary, 6 r/r) in the bemcentinib + LDAC group were evaluable for response and 4 (44%; 2 de novo + 2 relapsed) achieved rapid CRi at C2D1. Responses were durable (range: 7 – 11 cycles) in 3 of the 4 responders. A further 2 pts (22%, 1 secondary + 1 relapsed) achieved durable SD (5 and 6 cycles). mPFS among the 5 pts with durable CRi or SD was 5 months (range: 3.5-7.7). Further, at the time of writing, 11 pts (8 de novo, 3 r/r) in the bemcentinib + decitabine group were evaluable for response of which 4 (36%, all de novo) achieved CRi after ≥ 4 cycles. One additional de novo pt achieved durable SD lasting for 5 cycles. Conclusions: Bemcentinib in combination with LDAC exerted early durable responses in patients with both de novo and relapsed AML whilst the combination of bemcentinib + decitabine exerted comparably fewer and later responses in de novo AML. Soluble biomarker correlations will be presented at the meeting. Both combinations were generally well-tolerated and further exploration is warranted. Clinical trial information: NCT02488408.

Single Agent Ofatumumab In Patients With Relapsed and/Or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results From a Phase II Open Label Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5131-5131
Author(s):  
Jagoda Jasielec ◽  
David Peace ◽  
Sarah Edwards ◽  
Kathy Tolzien ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Open Label ◽  
Open Label Study ◽  
Large B Cell Lymphoma ◽  
Grade 3

Abstract Background Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains a clinical challenge, with no standard options for elderly or transplant-ineligible patients. Ofatumumab is a fully humanized monoclonal antibody with specificity for CD20 that is currently approved for R/R chronic lymphocytic leukemia. Ofatumumab given for 4 weekly doses elicited an overall response rate (ORR) of 11% in a prior French study of R/R DLBCL. However, a maintenance strategy for stable or responding DLBCL has not been tested and could improve the overall clinical benefit. This phase II open label study of single agent ofatumumab tested the efficacy of a combined induction and maintenance schedule. Methods Patients with R/R DLBCL who were transplant-ineligible or who had relapsed after transplantation were included. The treatment schedule was ofatumumab 1000 mg weekly for 8 weeks (induction phase). Patients achieving stable disease (SD) or better continued on a maintenance phase receiving ofatumumab at 1000 mg every other week until objective evidence of disease progression or patient/physician decision to withdraw. The primary end-points were overall response (OR) defined as the sum of partial response (PR) and complete response (CR) (Cheson Criteria), and toxicity using NCI criteria (CTCAE v.4). Secondary end-points included time to disease progression (TTP), overall survival (OS), and the overall clinical benefit defined as the sum of SD, CR, and PR. Results Eleven patients were enrolled in this trial before it was stopped due to slow accrual. Median age was 67 years (range: 41-89) and 4/11 patients were male. All patients had advanced stage III/IV disease and 10/11 had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median LDH was 246 U/l (range: 160-966), one patient had bulky disease, and one patient had B symptoms. Patients were heavily pre-treated with a median of 4 prior therapies (range: 1-7). One patient had relapsed disease, while the other 10 had disease that was rituximab-refractory. Four patients (36%) had prior transplants (2 autologous, 1 allogeneic, and 1 both). All patients were evaluable for response and toxicity. One patient was taken off study without progression due to hemolytic anemia (possibly related) after 6 months of therapy. Best responses achieved were 2 PR and 2 SD, while 7 patients progressed for an OR of 18% and a clinical benefit rate of 36%. Five patients (1 PD patient received maintenance ofatumumab inadvertently) went on to receive ofatumumab maintenance for a median duration of 4 cycles (range: 1-18). Response lasted for 6 and 9 months respectively in the 2 patients with PR. Subsequent therapies for progressing patients were offered (2 received bendamustine and rituximab, 1 received single agent bendamustine, and 3 had investigational therapies). At a median follow-up of 23 months (range: 5-38), 3 patients remain (27%) alive, median event free survival (EFS) was 2 months (range: 1-11), and median overall survival was 7 months (range: 1-31). Ofatumumab was generally well tolerated with 3 patients developing grade 1/2 infusion reactions. Other toxicities included grade 1/2 diarrhea (63%), anorexia (45%), hyponatremia (36%), and fatigue (36%). No grade 3/4 non-hematologic toxicities were observed. Grade 3/4 neutropenia occurred in 3/11 (27%) patients, one of whom was hospitalized for neutropenic fever. In addition, grade 4 thrombocytopenia occurred in 1 pt. Conclusion In this phase II study, we demonstrate modest single agent activity for ofatumumab in heavily pretreated rituximab-refractory DLBCL patients who have failed multiple standard therapies. Ofatumumab was well-tolerated with an acceptable safety profile. Maintenance therapy did not appear to add additional benefit in this small cohort. However, the favorable toxicity profile and modest clinical benefit justify further studies of this antibody in combination with chemotherapy or with other targeted agents. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau; GSK: Research Funding.

Everolimus and Reduced-Exposure Cyclosporine in de novo Renal-Transplant Recipients: A Three-Year Phase II, Randomized, Multicenter, Open-Label Study

2004 ◽  
Vol 78 (9) ◽  
pp. 1332-1340 ◽  
Author(s):  
Bj??rn Nashan ◽  
John Curtis ◽  
Claudio Ponticelli ◽  
Georges Mourad ◽  
Jonathan Jaffe ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Phase Ii ◽  
De Novo ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

scholarly journals A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn’s Disease: A Phase II, Open-Label Study

BioDrugs ◽  
2021 ◽  
Vol 35 (3) ◽  
pp. 325-336
Author(s):  
Irene Marafini ◽  
Carmine Stolfi ◽  
Edoardo Troncone ◽  
Elisabetta Lolli ◽  
Sara Onali ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase Ii ◽  
Induction Therapy ◽  
Open Label ◽  
Open Label Study ◽  
Label Study

795 A multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A843-A843
Author(s):  
Michael Wagner ◽  
Megan Othus ◽  
Sandip Patel ◽  
Christopher Ryan ◽  
Ashish Sangal ◽  
...  
Keyword(s):  
Phase Ii ◽  
Immune Checkpoint ◽  
Uv Light ◽  
Light Exposure ◽  
Case Reports ◽  
Objective Response ◽  
Open Label ◽  
Primary Tumors ◽  
Multicenter Phase ◽  
Grade 3

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

scholarly journals The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients

2021 ◽  
Author(s):  
Z Paul Lorenc ◽  
Jeffrey M Adelglass ◽  
Rui L Avelar ◽  
Leslie Baumann ◽  
Kenneth R Beer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Botulinum Toxin Type A ◽  
Study Drug ◽  
Botulinum Toxin Type ◽  
Second Phase ◽  
Repeat Dose ◽  
Serum Samples ◽  
Open Label ◽  
Blurred Vision ◽  
Line Scale

Abstract Background PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. Objectives The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. Methods This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. Results The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug–related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug–related AEs. Eight patients (1.4%) experienced study drug–related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. Conclusions The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

scholarly journals FIR: Efficacy, Safety, and Biomarker Analysis of a Phase II Open-Label Study of Atezolizumab in PD-L1–Selected Patients With NSCLC

2018 ◽  
Vol 13 (11) ◽  
pp. 1733-1742 ◽  
Author(s):  
David R. Spigel ◽  
Jamie E. Chaft ◽  
Scott Gettinger ◽  
Bo H. Chao ◽  
Luc Dirix ◽  
...  
Keyword(s):  
Phase Ii ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Biomarker Analysis

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

scholarly journals Carfilzomib Thalidomide and Dexamethasone Is Safe and Effective in the Treatment of Relapsed/Refractory Multiple Myeloma: An Open Label Phase II Australasian Leukaemia and Lymphoma Group (ALLG) MM 018/ Asian Myeloma Network (AMN) 002 Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Hang Quach ◽  
Simon J Harrison ◽  
Je-Jung Lee ◽  
Nichloas Murphy ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Board Of Directors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Research Funding ◽  
Open Label ◽  
Advisory Committees ◽  
Open Label Phase ◽  
Grade 3

Background: The combination of carfilzomib with immunomodulatory drugs (IMiDs) and dexamethasone is active in multiple myeloma (MM). Carfilzomib, thalidomide, and dexamethasone (KTd) has been studied in upfront MM treatment but has not been studied in the setting of relapsed/refractory myeloma (RRMM). The ALLG MM018/ AMN002 is an open-label phase II study of KTd in patients with RRMM. This study was conducted across 16 sites across Australia, New-Zealand, Singapore, South Korea and Taiwan. Method: Patients with RRMM with 1-3 prior lines of treatment were given carfilzomib [K: 20mg/m2 IV cycle 1 days 1 and 2, 56mg/m2 (36mg/m2 for patients age ≥75 years) from cycle 1 day 8 onwards], thalidomide (T: 100mg po nocte) and dexamethasone [dex: 40mg (20mg for patients age ≥75 years) po weekly], in a 28-day cycle. After 12 cycles, T was omitted, and K was given on days 1,2,15,16 and dex days 1,15 every 28-day cycles for a further six cycles. The primary endpoint was PFS. Secondary endpoints were ORR, overall survival, adverse events, and quality of life (QoL). The study had an 80% power to detect a ≥70% PFS at 6.5 months compared to historical ≤50% PFS at 6.5 months expected with Td (Kropff, M. et al. Haematologica 2012), at a significance level of 0.05. Results: This study has completed accrual. Eighty-three patients [median age of 66 years (42-85)] were enrolled with a median follow up of 15.9 (0.9-26) months. ORR rates were 86.4% (≥VGPR 70.2%). Median PFS was 20m (95% CI 15.9-26m). PFS at 6.5 months was 76.2% (95% CI 73.6-84.9%). Median OS has not been reached, and was 75% at 20 months. The most common grade ≥3/4 AEs were peripheral neuropathy (16%), upper respiratory tract infections (12%), dyspnoea (14%), and hypertension (10%). Grade ≥3/4 cardiac AEs occurred in 6%. The median carfilzomib dose that was delivered was 70.7% (32.8-92.6%) of the target dose. Thus far, 41% of patients have completed the intended 18 cycles of treatment. 21% of patients ceased therapy early. The most common reason for early treatment cessation was disease progression (30%) and adverse events (15%). Fifteen patients (18%) have died, 11 were due to MM, two from infection, one from an ischaemic cardiac event, and one from a traffic accident. QoL, as measured by the EQ-5D-5L instrument, remained stable throughout treatment. Conclusion: The ALLG MM018/AMN 002 study has met its primary endpoint. The KTd schedule as outlined in this study is efficacious in patients with RRMM, resulting in a prolonged PFS and a safety profile in line with previous reports for each of carfilzomib and thalidomide. KTd is an active option in jurisdictions where the cost of other IMiDs prohibits regulatory funding. Comparisons of efficacy and adverse events between the Caucasian and Asian populations will be presented at the meeting. Disclosures Quach: Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Sanofi: Consultancy, Research Funding. Harrison:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; Haemalogix: Consultancy. Augustson:Roche: Other: Support of parent study and funding of editorial support. Campbell:Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding; AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Soo:Hanmi: Research Funding. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

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