Building a Phase I Unit - file.bagevent.com · 5. Simplified reporting scheme that incorporates all...
Transcript of Building a Phase I Unit - file.bagevent.com · 5. Simplified reporting scheme that incorporates all...
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Building a Phase I Unit
Timothy A. Yap MBBS PhD MRCP
Medical Director, Institute for Applied Cancer ScienceAssociate Professor, Investigational Cancer Therapeutics
and Thoracic/Head & Neck Medical Oncology DepartmentsAssociate Director of Translational Research,
Khalifa Institute for Personalized Cancer Therapy
Shanghai, ChinaNovember 2018
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Disclosures
1. Employment: Medical Director of the Institute for Applied Cancer Science and Associate Director for Translational Research of the Institute for Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Center. Previous employee of the Institute of Cancer Research, London, UK
2. Research support: AstraZeneca, Bayer, Pfizer, Tesaro, Jounce, Eli Lilly, Seattle Genetics, Kyowa, Constellation, EMD Serono, Ipsen, Forbius (Formation Biologics), and Vertex Pharmaceuticals
3. Scientific Advisory Board Member: Pfizer, Atrin, Bayer, Cybrexa, and Seattle Genetics
4. Consultancies: Aduro, Almac, AstraZeneca, Atrin, Bayer, Bristol-Myers Squibb, Calithera, Clovis, Cybrexa, EMD Serono, Ignyta, Jansen, Merck, Pfizer, Roche, Seattle Genetics, and Vertex Pharmaceuticals
5. Speaker Bureau: AstraZeneca, Merck, Pfizer, and Tesaro
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It’s About Building Bridges
Hong Kong-Zhuhai-Macau Bridge
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Building Bridges for Drug DevelopmentThe Most Important Players
Phase I
Preclinical Clinical
Pharma Regulatory
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Building Bridges for Drug DevelopmentNavigating The Roadway
• Regulatory issues
• Business office
• Contiguity
• Multidisciplinary care
• Funding
• Space
• Staff
• Training
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The Cancer Center
• Integrated free-standing center with a single mission – “Making Cancer History”
• 20,000 staff members• ~1,600 outstanding scientists and
physicians• Largest number of NCI grants and grant
dollars for cancer research• Research-driven multidisciplinary care of
over 30,000 new cancer patients each year• Largest therapeutic cancer clinical trials
center internationally
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MD Anderson Cancer CenterPatient Care Statistics
Total patients served ~137,000
New patients served >44,000
Patients enrolled in clinical trials >10,800
Number of clinical trials 1,255
Ambulatory care visits 1,441,403
FY17
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To become the premier Investigational Cancer Therapeutics Program in the world through:• state of the art research-driven patient care• novel molecular therapeutics • biomarker-driven clinical trials
VISION
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MISSION
• To translate laboratory discoveries and clinical observations into hypothesis-driven clinical trials leading to targeted, personalized cancer treatments
• To collaborate with clinicians and researchers in the DoCM and throughout the institution to: o expedite time from preclinical concept to trial o increase access to new molecular entitieso expedite discovery of right drug for right patiento expedite Phase I/II/III transition
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Department of Investigational Cancer Therapeutics (A Phase I Program)
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Department of Investigational Cancer Therapeutics
Clinical Center for Targeted Therapy(CCTT Outpatient Clinic)
Dept. Core Laboratory
Clinical Translational Research Center (CTRC)
Phase I Inpatient
Departmental Resources
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• Over 1500 patients enrolled on phase 1 trials in 2017• No rare tumor: 90+ tumor types seen• Competitive activation times
– Can submit before IND approval
• Competitive enrollment • Dedicated infusion unit, inpatient service, lab• Molecular profiling initiative to profile all patients
Dept. of Investigational Cancer Therapeutics Distinguishing Features
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Patient Distribution by Tumor Type9/1/2014 to 8/31/2018
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Trial Portfolio: Areas of Emphasis
• Studies with new first-in-human molecules– Trials that we can help develop
• Hypothesis-driven trials of new combinations of experimental or approved drugs– Combinations based on MD Anderson preclinical data
• Signal seeking histology-independent or multiple histology biomarker-selected basket trials
• Protocols using new routes of delivery of drugs• Biomarker discovery and pharmacodynamic effects
– Learning more from our trials– Responders vs non-responders– Mechanisms of acquired resistance
• IPCT Unusual responder program
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Number of ICT Clinical Trials Activated and Submitted per FY
*Data as of Aug 31
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Number of Active Trials by Agent & Phase
72
47
27
31
*Data as of Aug 31
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Number of Active Trials by Drug Type
9078
9
*Data as of Aug 31
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Unique Targets
ØAurora kinaseØDeath receptorØBRAFØCDKØEGFR familyØFarnesyltransferaseØFGFRØGamma secretaseØHDACØHIF-1aØIL-1aØIL-6ØIGFRØAnti-CD30ØTGF-bØNFkB
ØKIT kinaseØMET kinaseØMEKØmTORØPI3KØProteosomeØRAF kinaseØRET kinaseØSTAT3ØSRC KinaseØTubulinØVEGFRØEIF-4EØAKTØCHK-1,2ØNFR-1
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Unique Department Organizational Structure
• Physician-based Research Teams– Each team has a study coordinator and research nurse team,
regulatory team, data team, finance Lead– Full independence– Entrepreneurial environment– Most teams have focused research themes: for example…
• Team Yap: DNA damage response (DDR); IO agents; thoracic• Team Subbiah: RET; sarcomas• Team Hong: T-cell therapies, NTRK• Team Meric: Intratumor agents• Team Naing: IO agents
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Processes to Ensure Quality
• Team structure allows for accountability• Institution wide auditing process• M&M board review toxicities/SAEs• Quarterly Dose error meetings
• QIAC: centralized tumor measurements– RECIST1.1– RECIST1.1/irRC– irRC– RANO
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Clinical and Translational Research Center(CTRC)
• Phlebotomy• IV infusion• Specimen processing• Research EKGs• Coordinator time-sensitive and complex research• Accommodate 24 hour PKs
Dedicated unit for intensive treatment and monitoring of patients participating in complex, early-phase clinical trials.
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CTRC “Fast Facts”
28-bed and 4-chair Total full-time employees: CTRC Treatment Center: 44CTRC Laboratory = 54 (and 2 part-time)
Protocol enrollments (Sep 2012 – Aug 2017) § 8,552 total enrollments to CTRC studies § 701 enrollments on NIH-sponsored, Cooperative Group § 18 CCSG programs served in last 5 years
FDA approved 76 drugs studied in the CTRC in last 5 years
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Investigator-Initiated Trials in ICT Bringing a concept from bench to bedside
Scientific concept
From concept to trial design
Build study team and write letter
of intent
Pharmaceutical partnership or other support
Trial implementation
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What Metrics are Important?
• Quality of work:– Data quality – accurate and on time– Lack of protocol deviation and violations– Meeting deadlines– Outstanding care and follow up of patients– Professionalism and attitude of team
• Accrual• Efficiency • Scientific input and engagement• Cost
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Integrating translational medicine capability
Doc, you must know everything!
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Requirements for Handling NGS “Big Data”1. Inhouse resource that provides physicians with a clear understanding of which genomic
alterations are actionable at a gene and variant level (i.e. don’t leave it up to the physicians to guess!)
2. Resource that matches clinically available therapies with specific genotypes (at a variant level)
3. Resource that provides concise representation of the level of evidence associated with each therapy within the patient’s genomic and tumor context (keep it simple and evidence-based)
4. Resource for identifying genotype-relevant clinical trials (ideally open access for all)
5. Simplified reporting scheme that incorporates all this information in a patient-specific report (simple and user friendly)
6. Timely proactive notification of actionable genomic alterations identified and potential courses of action (must be in real time and must be a plan of action, e.g. trial or no trial)
Precision Oncology Decision Support System (PODSS) set up to improve clinical utilization of molecular testing
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Institute for Personalized Cancer TherapiesGenomics Decision Support
• Prospective tumor characterization for patient enrichment in targeted therapy trials and validation of predictive biomarkers– Clearinghouse study
• Discovery of biomarkers of sensitivity and resistance in ongoing trials and in standard of care therapy– Unusual responder program
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• Identifying potential actionable aberrations• Incorporating patient and previous treatment information• Leveraging information in published literature and other
online biomedical data • Prioritization of mutations/targets• Identifying optimal approved or investigational treatment
Institute for Personalized Cancer TherapiesGenomics Decision Support
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1. Resource that provides physicians with a clear understanding of which genomic alterations are actionable at a gene and variant level
2. Resource that matches clinically available therapies with specific genotypes
3. Resource that provides concise representation of the level of evidence associated with each therapy within the patient’s genomic context
4. Resource for identifying genotype-relevant clinical trials
5. Simplified reporting scheme that incorporates all this information in a patient-specific report
6. Timely proactive notification of actionable genomic alterations identified and potential courses of action
Precision Oncology Decision Support CASE STUDY
Decision Support Requires More that Delivery of Mutation Information
How can we help clinicians interpretresults and rapidly identify the best
treatment options available?
First 14K patients tested = >6,000mutations found
Molecular Reports issued by MDL include genes altered (pg. 2) with specific alterations listed (pg. 3 and beyond)
Unmatched therapy Matched therapy
Institute for Personalized Cancer TherapiesGenomics Decision Support
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Ann Bailey, PhDJia Zeng, PhD Vijaykumar Holla, PhD Amber Johnson, PhD
Beate Litzenburger, PhD
Yekaterina Khotskaya, PhD
Precision Oncology Decision Support (PODS) Team
Nora Sanchez, PhD Lauren Brusco, PhD
REAL PEOPLE, NOT MACHINES
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Communicating Annotations in Real Time in Effective Reporting Format
Level I Indication: standard of care
Resistance mutations clearly highlighted
Variants of unknown significance are deprioritized
Personalizedcancertherapy.org
Website: 33 genes fully annotated>1,025 functionally significant SNVs>15,000 SNVs reviewed
Single Patient Annotation Effort: 3200 Single patients annotated
Drug Curation Effort: 1504 drugs annotated
Clinical Trial Curation Effort: 3240 cancer clinical trials annotated
Precision Oncology Decision Support (PODS) Team
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Strategy 1. Data in real time: Patient Report within 1 business day
Clear Alteration-Level Actionability Calls
Aggregated Frequencies
Emailed and Deposited into EHRClear Functional
Significance Call
Variant-level annotations
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Trials retrieved only if targets a potentially actionable or actionable alteration
Strategy 2. Patient Report: Are There Clinical Trials Available? (that are active & have open slots)
Display only what is relevant to patient
Relevant drug underlined
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Based on Variant Actionability
On-demand link for screening
Strategy 3. Clinical Trial Email Alert to Patient’s Oncologist and Trial PI
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Thank you
MD Anderson Department of Investigational Cancer Therapeutics (A Phase I Program)