scholarly journals P653 Efficacy and safety of an additional 8 weeks of tofacitinib induction therapy: Updated results of the OCTAVE Open study for tofacitinib 8-week induction non-responders

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S537-S539
Author(s):  
D T Rubin ◽  
M C Dubinsky ◽  
S Danese ◽  
R Saad-Hossne ◽  
D Ponce de Leon ◽  
...  
Keyword(s):  
Clinical Response ◽  
Mucosal Healing ◽  
Published Data ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Safety Risks ◽  
Number Of Patients ◽  
Factor Inhibitor ◽  
Induction Current

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were demonstrated in three Phase 3, randomised, placebo-controlled trials in patients with moderate to severe UC.1 Patients who received tofacitinib 10 mg twice daily (BID) for 8 weeks (weeks) in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951) and did not achieve a clinical response (ie induction non-responders [IndNR]) could enter an ongoing, Phase 3, open-label, long-term extension (OLE) study (OCTAVE Open; NCT01470612). We present an update, as of May 2019, of previously published data up to December 2016 from the OLE study for IndNR patients.2 Methods IndNR patients received tofacitinib 10 mg BID in the OLE study. Patients who were still non-responders after an additional 8 weeks of induction were required to discontinue. Clinical response, remission and mucosal healing were evaluated up to Month (M)36 of the OLE study. Adverse events (AEs) and serious AEs (SAEs) are also presented. Results 429 IndNR patients enrolled in the OLE study, 295 of which received tofacitinib 10 mg BID during induction trials (Table). The proportions of patients with prior tumour necrosis factor inhibitor and baseline corticosteroid use were slightly higher in non-responders than responders at M2; other baseline characteristics were generally similar in responders and non-responders. At M2, 59.7%, 25.7% and 16.2% of patients achieved clinical response, mucosal healing and remission, respectively (as observed). Corresponding non-responder imputation and last observation carried forward values were 52.2%, 23.1% and 14.2% (Table). The table shows data up to M36. The proportions of patients with AEs, SAEs and discontinuations due to AEs for IndNR patients censored at M2 (52.2%, 3.7% and 2.4%, respectively) were similar to those for all patients in OCTAVE Induction 1 and 2 (tofacitinib: 55.4%, 3.8% and 3.9%; placebo: 56.4%, 6.0% and 4.3%), with no new safety risks identified (table). Conclusion The majority of patients who did not achieve clinical response to tofacitinib 10 mg BID for 8 weeks in the induction studies – and subsequently received an additional 8 weeks of tofacitinib 10 mg BID in the OLE study—achieved clinical response, with a considerable number of patients in remission and/or mucosal healing at M36. No new safety risks were observed in the additional 8 weeks of induction. These data support extended induction with an additional 8 weeks of tofacitinib for non-responders to 8-week induction. Current product labelling recommends 5 mg BID for maintenance in responders.3,4 References

scholarly journals P334 Impact of disease duration on tofacitinib efficacy in patients with ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S321-S323
Author(s):  
S Travis ◽  
I Dotan ◽  
S Danese ◽  
M Chiorean ◽  
J Yamamoto-Furusho ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Disease Duration ◽  
Small Sample Size ◽  
Mucosal Healing ◽  
Small Sample ◽  
Open Label ◽  
Phase 3 ◽  
Two Phase ◽  
The Impact

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib in patients with UC were evaluated in two Phase 3 induction studies (OCTAVE Induction 1 and 2; NCT01465763, NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574) [1], and an ongoing, open-label, long-term extension study (NCT01470612) [2]. We evaluated the impact of disease duration on tofacitinib efficacy in the OCTAVE trials. Methods Patients received tofacitinib 10 mg twice daily (BID) or placebo in OCTAVE Induction 1 and 2, and responders at Week 8 were eligible to receive tofacitinib 5 or 10 mg BID or placebo during OCTAVE Sustain (final efficacy assessment at Week 52). Non-responders from OCTAVE Induction 1 and 2 and completers/treatment failures from OCTAVE Sustain could enter the OLE study. In the OLE study, patients who did not show clinical response to 8 weeks of tofacitinib 10 mg BID in OCTAVE Induction 1 and 2 (induction non-responders [IndNR]) received an additional 8 weeks of tofacitinib 10 mg BID; all patients underwent endoscopy at Month 2 (data as of Sep 2018). Patients were stratified by UC disease duration (<3, 3–6 and >6 years) at OCTAVE Induction 1 and 2 baseline (ie prior to study treatment). Associations between disease duration category and efficacy endpoints were assessed using the Cochran-Mantel–Haenszel Chi-square test. Results Among patients who received tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, remission and mucosal healing rates at Week 8 were numerically higher in those with shorter disease duration than those with longer disease duration, but associations were not statistically significant (Table). Clinical response rates were similar across disease duration categories. At Week 52 of OCTAVE sustain, remission and mucosal healing rates were highest in patients with the shortest disease duration (<3 years; Table). Among IndNR, the proportions of patients achieving efficacy endpoints at Month 2 of the OLE study were lowest in those with disease duration <3 years, but associations were not statistically significant (Table). Conclusion In general, disease duration did not impact tofacitinib efficacy. Patients diagnosed with UC <3 years prior to starting tofacitinib treatment were numerically more likely to achieve remission and mucosal healing in induction and maintenance trials than those with longer disease duration, but the associations were not statistically significant. These analyses are post hoc and limited by the small sample size, and further data are needed to understand whether disease duration may have an impact on the response to tofacitinib treatment. References

scholarly journals Efficacy and safety of secukinumab in Japanese patients with active ankylosing spondylitis: 24-week results from an open-label phase 3 study (MEASURE 2-J)

2019 ◽  
Vol 30 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Mitsumasa Kishimoto ◽  
Atsuo Taniguchi ◽  
Ayako Fujishige ◽  
Shuhei Kaneko ◽  
Sibylle Haemmerle ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Phase

scholarly journals 354 Lenvatinib and pembrolizumab in advanced endometrial carcinoma (EC): long-term efficacy and safety update from a phase 1b/2 study

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A381-A381
Author(s):  
Vicky Makker ◽  
Carol Aghajanian ◽  
Allen Cohn ◽  
Margarita Romeo ◽  
Raquel Bratos ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Center ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Efficacy Analysis ◽  
Phase 1B ◽  
Grade 3 ◽  
Cutoff Date

BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. Pembrolizumab is an anti-programmed death-1 monoclonal antibody. We previously reported results from a cohort of 108 patients with metastatic EC (data cutoff date, January 10, 2019) who received lenvatinib + pembrolizumab as part of an ongoing multicenter, open-label, phase 1b/2 study evaluating the combination treatment in patients with selected solid tumors (NCT02501096). Lenvatinib + pembrolizumab showed a tolerable safety profile and promising antitumor activity per immune-related (ir) Response Evaluation Criteria In Solid Tumors (RECIST) by investigator assessment, including an objective response rate (ORR) of 38.9% (95% confidence interval [CI], 29.7–48.7), median progression-free survival (PFS) of 7.4 months (95% CI, 5.3–8.7), and median overall survival (OS) of 16.7 months (95% CI, 15.0-not estimable).1 Here we present updated efficacy and safety data (data cutoff date: August 18, 2020).MethodsPatients included in the EC cohort had histologically confirmed, measurable metastatic EC and had received ≤2 prior chemotherapies (unless discussed with the sponsor). Patients received lenvatinib (20 mg orally once daily) and pembrolizumab (200 mg intravenously once every 3 weeks). The phase 2 efficacy endpoints included ORR, PFS, OS, and duration of response. Tumor assessments for primary and secondary endpoints were evaluated by investigators per irRECIST.ResultsThe 108 patients from the key efficacy analysis set for the previously reported results were all included in these updated analyses. Median follow-up duration for the study was 34.7 months. Efficacy outcomes are summarized in table 1. Treatment-related adverse events (TRAEs) occurred in 104 (96%) patients (94 [87%] grade ≤3, 10 [9%] grade ≥4). TRAEs led to study-drug interruption of 1 or both drugs in 80 (74.1%) patients and dose reductions of lenvatinib in 73 (67.6%) patients; 23 (21.3%) patients discontinued 1 or both drugs due to a TRAE. The most common grade ≥3 TRAEs were hypertension (33.3%), lipase increased (9.3%), fatigue (8.3%), and diarrhea (7.4%).Abstract 354 Table 1ConclusionsWith extended follow-up, our updated efficacy analysis continued to show clinical benefit in patients with metastatic EC who received lenvatinib + pembrolizumab. Moreover, the combination had a manageable safety profile that was generally consistent with the established safety profiles of the individual monotherapies. No new safety signals were detected. A phase 3 study of lenvatinib + pembrolizumab versus treatment of physician’s choice in advanced endometrial cancer further supports the lasting clinical benefits observed in our study.2Trial Registration www.clinicaltrials.gov NCT02501096ReferencesMakker V, Taylor MH, Aghajanian C, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 2020;38(26):2981–2992.Makker V, Colombo N, Casado Herráez A, et al. A multicenter, open-label, randomized, phase 3 study to compare Ethics ApprovalThis study was approved by the following ethics committees/institutional review boards (IRBs): Oregon Health & Sciences University IRB, IntegReview IRB, Memorial Sloan Kettering Cancer Center IRB, University of Pennsylvania Office of Regulatory Affairs IRB, Dana-Farber Cancer Institute IRB, The University of Chicago Biological Sciences Division IRB, University of Texas MD Anderson Cancer Center IRB, Western IRB, Quorum Review IRB, US Oncology, Inc. IRB, CEIm - Comité de Ética de la Investigación con Medicamentos, Regional Komite for Medisinsk og Helsefagli Forskningsetikk, and REC - Regional Committees for Medical and Health Research Ethics. All participants gave informed consent before taking part in this study.ConsentNo identifying information is contained in this abstract so no permission from participants is considered necessary.

Sign in / Sign up

Export Citation Format

Share Document