Adaptive Design: Controversies and Progress

2013 ◽  
pp. 31-42
Keyword(s):  
Adaptive Design

426 MK-3475-U02: Phase 1/2 study of investigational agents with or without pembrolizumab versus pembrolizumab monotherapy in melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A451-A451
Author(s):  
Reinhard Dummer ◽  
Georgina V Long ◽  
Anna Pavlick ◽  
Michael Postow ◽  
Antoni Ribas ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Adaptive Design ◽  
Phase 1 ◽  
Objective Response ◽  
End Points ◽  
Investigational Agent ◽  
Link Type ◽  
Programmed Death ◽  
Investigational Agents ◽  
Study Intervention

BackgroundPembrolizumab is a standard of care for the treatment of unresectable or metastatic melanoma and an adjuvant treatment of melanoma with involvement of lymph node(s) following complete resection. However, new treatment options are needed to reduce the tumor burden before surgery and improve overall outcomes in patients with advanced melanoma.MethodsMK-3475-U02 is a phase 1/2, rolling arm, multicenter, open-label, adaptive design study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab or pembrolizumab alone for the treatment of melanoma. Patients will be enrolled in 1 of the 3 substudies. Substudy 02A will include patients with programmed death-1 (PD-1)–refractory melanoma (progressed after ≥2 doses of anti-PD-1/programmed death ligand-1 [PD-L1] therapy) randomized equally to treatment arms evaluating ≥1 investigational agent(s) with or without pembrolizumab. Enrollment is planned for up to ~100 patients per arm.Substudy 02B will include patients with unresectable stage III or stage IV melanoma not amenable to local therapy. Patients will be randomized 2:1 to combination (≥1 investigational agent(s) with or without pembrolizumab) or monotherapy (pembrolizumab alone) stratified by baseline lactate dehydrogenase status (normal/elevated) and prior adjuvant therapy with a PD-1 inhibitor (yes/no). Enrollment is planned for ~90 patients in the combination arm and ~45 in the control arm.Substudy 02C will include patients with stage IIIB/IIIC/IIID melanoma who are candidates for neoadjuvant therapy. Patients will be randomly assigned to combination (≥1 investigational agent(s) with or without pembrolizumab) or monotherapy (pembrolizumab alone). Surgical resection will be performed 6 weeks after the first dose of neoadjuvant study intervention. Enrollment is planned for ~25 patients in combination and ~15 in the pembrolizumab monotherapy arms.Treatment will continue for up to 2 years (up to 1 year neoadjuvant/adjuvant therapy for substudy 02C), until disease progression, unacceptable toxicity, or study discontinuation. The primary end points include safety (adverse events and study intervention discontinuations) for all 3 substudies; objective response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumors 1.1 for substudies 02A and 02B, and pathological complete response (pCR) as assessed by central review of the pathology results for substudy 02C. Secondary end points include duration of response for substudies 02A and 02B, and recurrence-free survival, near pCR, and pathological partial response rates for substudy 02C.ResultsN/AConclusionsN/AAcknowledgementsThe authors thank the patients and their families for participating in these trials and all investigators and site personnel. Medical writing and/or editorial assistance was provided by Neha Tuli-Wildemore, MBBS, PhD, and Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT04305041, NCT04305054, NCT04303169Ethics ApprovalThe study protocol and all amendments were approved by the relevant Institutional Review Board or ethics committee at each study site. All patients provided written informed consent to participate in the clinical trial.ConsentN/AReferencesN/A

scholarly journals The Transformative Potential of Ruins: A Tool for a Nonlinear Design Perspective in Adaptive Reuse

2021 ◽  
Vol 13 (10) ◽  
pp. 5660
Author(s):  
Elena Guidetti ◽  
Matteo Robiglio
Keyword(s):  
Adaptive Design ◽  
Future Research ◽  
Existing Buildings ◽  
Quantitative And Qualitative Research ◽  
Transformative Potential ◽  
Nonlinear Design ◽  
Mental Construct ◽  
Design Perspective ◽  
Novel Concept ◽  
The Relationship

In recent years, the heritage preservation debate has seen a growing interest in emerging theories in which the concept of potential plays an essential role. Starting from the assumption that memory is an evolving mental construct, the present paper introduces the concept of “transformative potential” in existing buildings. This novel concept regards the inevitability of loss and the self-destructive potential as part of the transformation of each building. The “transformative potential” is defined here as the relationship between spatial settings and material consistency. This research hypothesizes five “transformative potential” types by analyzing five best-practices adapted ruins in the last 15 years. The analysis integrates quantitative and qualitative research methods: morphological analysis (dimensional variations, critical redrawing, configuration patterns) and decay stages evaluation (shearing layers analysis, adaptation approaches). The goal is to test the “transformative potential” effectiveness in outlining patterns between specific stages of decay and adaptive design projects. Adaptation projects may actualize this potential in a specific time through incremental and decremental phases, outlining a nonlinear relationship between decay and memory. The study provides insights for future research on adapting existing buildings in a particular decay stage.

Optimizing adaptive design for Phase 2 dose-finding trials incorporating long-term success and financial considerations: A case study for neuropathic pain

2017 ◽  
Vol 57 ◽  
pp. 69-86
Author(s):  
Jingjing Gao ◽  
Narinder Nangia ◽  
Jia Jia ◽  
James Bolognese ◽  
Jaydeep Bhattacharyya ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Adaptive Design ◽  
Dose Finding ◽  
Phase 2
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