8 results on '"Geoffrey Kim"'
Search Results
2. Data from An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies
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Reena Philip, Richard Pazdur, Geoffrey Kim, Amy E. McKee, Gideon M. Blumenthal, Abraham Tzou, and Julia A. Beaver
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As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges, including analytic performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the FDA. These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. Clin Cancer Res; 23(6); 1368–72. ©2016 AACR.
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- 2023
3. FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation–Associated Advanced Ovarian Cancer
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Sanjeeve Balasubramaniam, Rosane Charlab, Sara Horton, Chao Liu, Hisani N. Horne, Robert N. Schuck, Kim J. Robertson, Laura L. Fernandes, Julia A. Beaver, William F. Pierce, Anamitro Banerjee, Todd R. Palmby, Xiao Hong Chen, Geoffrey Kim, Jingyu Yu, Pengfei Song, Kirsten B. Goldberg, Eunice Y. Lee, Richard Pazdur, Jinzhong Liu, Rajeshwari Sridhara, Haw Jyh Chiu, Reena Philip, Shenghui Tang, Xing Wang, and Sarah J. Schrieber
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Abdominal pain ,Nausea ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Rucaparib ,Gynecology ,business.industry ,BRCA mutation ,Cancer ,medicine.disease ,Dysgeusia ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,medicine.symptom ,Ovarian cancer ,business ,Companion diagnostic - Abstract
On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)–associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDxBRCA test (Foundation Medicine, Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation–associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 patients with ovarian cancer treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% [57/106; 95% confidence interval (CI), 44–64], and median duration of response was 9.2 months (95% CI, 6.6–11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (≥20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval. Clin Cancer Res; 23(23); 7165–70. ©2017 AACR. See related commentary by Kohn et al., p. 7155
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- 2017
4. FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer
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Jeanne Fourie Zirkelbach, Shenghui Tang, Laleh Amiri-Kordestani, Amanda J. Walker, Wentao Fu, Amy Tilley, Amy E. McKee, Erik Bloomquist, Todd R. Palmby, Qi Liu, Suparna Wedam, Richard Pazdur, Wei Chen, Geoffrey Kim, Paul G. Kluetz, and Rajeshwari Sridhara
- Subjects
Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Pyridines ,Receptor, ErbB-2 ,Breast Neoplasms ,Context (language use) ,Palbociclib ,Neutropenia ,Disease-Free Survival ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,medicine ,Humans ,Drug Approval ,Fulvestrant ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Gynecology ,Estradiol ,business.industry ,Letrozole ,Cancer ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Female ,Receptors, Progesterone ,business ,medicine.drug - Abstract
On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36–0.59; P < 0.0001]. Safety data confirmed the known adverse reaction profile of palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968–72. ©2016 AACR.
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- 2016
5. Dose Finding of Small-Molecule Oncology Drugs: Optimization throughout the Development Life Cycle
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Rajeshwari Sridhara, Pasi A. Jänne, Alice T. Shaw, Geoffrey Kim, Amy E. McKee, and Richard Pazdur
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Drug ,Cancer Research ,medicine.medical_specialty ,media_common.quotation_subject ,Antineoplastic Agents ,Pharmacology ,Regulatory Application ,030226 pharmacology & pharmacy ,Software development process ,03 medical and health sciences ,Dose finding ,0302 clinical medicine ,Dosing schedules ,Neoplasms ,Humans ,Medicine ,Molecular Targeted Therapy ,Dosing ,Intensive care medicine ,Drug Approval ,Protein Kinase Inhibitors ,media_common ,High rate ,Clinical Trials as Topic ,Dose-Response Relationship, Drug ,business.industry ,Oncology ,030220 oncology & carcinogenesis ,business ,Oncology drugs - Abstract
In the current era of rapid marketing approval for promising new products in oncology, dose finding and optimization for small-molecule oncology drugs occurs throughout the development cycle and into the postmarketing setting. Many trials that support a regulatory application have high rates of dose reductions and discontinuations, which may result in postmarketing requirements (PMR) to study alternate doses or dosing schedules. Kinase inhibitors particularly have been susceptible to this problem, and among the 31 approved drugs of this class, the approvals of eight have included such PMRs and/or commitments. Thus, the current paradigm for dose finding and optimization could be improved. Newer strategies for dose finding rather than traditional 3 + 3 designs should be considered where feasible, and dose optimization should be continued after phase I and throughout development. Such strategies will increase the likelihood of a right dose for the right drug at the time of regulatory approval. Clin Cancer Res; 22(11); 2613–7. ©2016 AACR. See all articles in this CCR Focus section, “New Approaches for Optimizing Dosing of Anticancer Agents.”
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- 2016
6. Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms
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Ann T. Farrell, Geoffrey Kim, Patricia Keegan, Laura Lee Johnson, Rajeshwari Sridhara, Elektra J. Papadopoulos, Wen-Hung Chen, Richard Pazdur, Martha Donoghue, Virginia E. Kwitkowski, Ashley F. Slagle, and Paul G. Kluetz
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Cancer Research ,medicine.medical_specialty ,media_common.quotation_subject ,Alternative medicine ,MEDLINE ,Disease ,Physical function ,Article ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Quality (business) ,Patient Reported Outcome Measures ,030212 general & internal medicine ,Adverse effect ,media_common ,Clinical Trials as Topic ,business.industry ,Cancer ,medicine.disease ,Patient Outcome Assessment ,Oncology ,030220 oncology & carcinogenesis ,Quality of Life ,Physical therapy ,business - Abstract
Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess the efficacy of a drug. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts: symptomatic adverse events, physical function, and disease-related symptoms, which are key contributors to the effect of a therapy on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials. Clin Cancer Res; 22(7); 1553–8. ©2016 AACR.
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- 2016
7. Expansion Cohorts in First-in-Human Solid Tumor Oncology Trials
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Meredith K. Chuk, Marc R. Theoret, Tatiana M. Prowell, Patricia Keegan, Sanjeeve Balasubramaniam, Richard Pazdur, Paul G. Kluetz, Geoffrey Kim, Kim Ts, and Lee Pai-Scherf
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Drug ,Oncology ,Cancer Research ,medicine.medical_specialty ,media_common.quotation_subject ,Alternative medicine ,MEDLINE ,Phases of clinical research ,Antineoplastic Agents ,Medical Oncology ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Solid tumor ,media_common ,Clinical Trials as Topic ,United States Food and Drug Administration ,business.industry ,Clinical study design ,Drugs, Investigational ,United States ,Clinical trial ,Drug development ,business - Abstract
In 1962, the passage of the Kefauver–Harris Amendment to the 1938 Food, Drug, and Cosmetic Act required that sponsors seeking approval of new drugs demonstrate the drug's efficacy, in addition to its safety, through a formal process that includes “adequate and well-controlled” clinical trials as the basis to support claims of effectiveness. As a result of this amendment, FDA formalized in regulation the definitions of various phases of clinical investigations (i.e., phase I, phase II, and phase III). The clinical drug development paradigm for anticancer drugs intended to support marketing approval has historically followed this “phased” approach with sequential, stand-alone trials, with an increasing number of patients exposed to an investigational drug with each trial in order to fulfill the objectives of that particular stage in development. Increasingly, it is the Office of Hematology and Oncology Products' experience that commercial sponsors of solid tumor oncology drug development programs are amending ongoing phase I trials to add expansion cohorts designed to evaluate study objectives typical of later-phase trials. For investigational anticancer drugs that demonstrate preliminary clinical evidence of substantial antitumor activity early in clinical testing, use of expansion cohorts as a component of the solid tumor oncology drug development pathway, with appropriate measures to mitigate the risks of this approach, may fit in well with the goals and concepts described by FDA's expedited programs for serious conditions.Clin Cancer Res; 21(20); 4545–51. ©2015 AACR. See all articles in this CCR Focus section, “Innovations to Speed Drug Development.”
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- 2015
8. Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary
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Wendy Wilson, Amna Ibrahim, Anthony J. Murgo, Brenda Gehrke, Suchitra Balakrishnan, Katherine Thornton, Shenghui Tang, Richard Pazdur, Anshu Marathe, Geoffrey Kim, Pengfei Song, Debasis Ghosh, Christine Garnett, Robert Justice, V. Ellen Maher, Brian Booth, John Duan, Young Jin Moon, Leigh Verbois, Qi Liu, Robert Dorsam, Lisa Skarupa, Somesh Chattopadhyay, Sarah Pope Miksinski, Hao Zhu, and Haripada Sarker
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Cancer Research ,medicine.medical_specialty ,Vandetanib ,Placebo ,QT interval ,Sudden death ,Disease-Free Survival ,law.invention ,Piperidines ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Thyroid Neoplasms ,Drug Approval ,United States Food and Drug Administration ,business.industry ,Hazard ratio ,Medullary thyroid cancer ,medicine.disease ,Rash ,United States ,Carcinoma, Neuroendocrine ,Surgery ,Oncology ,Quinazolines ,medicine.symptom ,business ,medicine.drug - Abstract
On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24–0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease. Clin Cancer Res; 18(14); 3722–30. ©2012 AACR.
- Published
- 2012
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