Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

INTRODUCTION

  • Org Study ID: TPU-TAS-120-101
  • Secondary ID: 2013-004810-16
  • NTC ID: NCT02052778
  • Sponsor: Taiho Oncology, Inc.

BRIEF SUMMARY


This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2
study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the
safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients
with advanced solid tumors with and without FGF/FGFR-related abnormalities.

The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D
of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to
further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring
specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas ,
urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or
amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion;
and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors
harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

DETAILED DESCRIPTION


Phase 1 Dose Escalation Phase 1 Dose Escalation has been completed as of Dec 2017

Phase 1 Dose Expansion: (CLOSED)

Up to approximately 185 patients will be enrolled among the 8 groups as outlined below:

- Group 1- CCA (iCCA or eCCA) with FGFR2 gene fusions.

- Group 2- CCA (iCCA or eCCA) with FGFR2 gene fusions that are chemotherapy naive or
intolerant to first line chemotherapy (i.e., on chemotherapy regimen ≤ 1 cycle).

- Group 3 - CCA (iCCA or eCCA) with FGFR2 gene fusions treated with prior FGFR inhibitors.

- Group 4 - CCA (iCCA or eCCA) with other FGFR2 abnormalities, ie, gene mutations,
rearrangements or amplifications.

- Group 5 - GBM or grade III glioma (i.e, anaplastic astrocytoma or anaplastic
oliogodendroglioma) with FGFR gene fusions or activating mutations

- Group 6 - Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating
mutations.

- Group 7: Basket of tumor types with tumors harboring FGFR2 amplification (≥10 copies).

- Group 8 - Basket of tumor types (except CCA, brain tumors and advanced urothelial
carcinomas) with tumors harboring FGFR gene fusions or activating mutations.

Phase 2:

Approximately 100 iCCA patients with confirmed FGFR2 gene fusions will be treated. Patients
will be centrally screened for FGFR2 gene fusions. This is a Single arm study with the
primary endpoint of ORR.


  • Overall Status
    Recruiting
  • Start Date
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1 - Overall Response Rate (ORR)

Primary Outcome 1 - Timeframe: 12 months

Primary Outcome 2 - Measure: Phase 1 - Early Progression Rate (EPR) for GBM or grade III glioma

Primary Outcome 2 - Timeframe: 12 months

Primary Outcome 3 - Measure: Phase 2 - Overall Response Rate (ORR)

Primary Outcome 3 - Timeframe: 12 months

CONDITION

  • Cholangiocarcinoma
  • Brain Tumor
  • Urothelial Cancer
  • Other Tumor Types With FGFR2 Gene Fusions
  • Activating Mutations
  • FGFR2 Amplification

ELIGIBILITY


Inclusion Criteria:

Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting
the following criteria:

Phase 1 Expansion

1. Patient has failed all standard therapies or standard therapy does not exist or is not
tolerated.

2. Patient has specific FGF/FGFR aberrations

- Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other
FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or
amplifications

- Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic
oligodendroglioma) with FGFR gene fusions or activating mutations.

- Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations

- All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (≥ 10
copies), FGFR gene fusions, or FGFR activating mutations

Phase 2

1. Patient has histologically or cytologically confirmed, locally advanced, metastatic,
unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by
the Sponsor's designated central laboratory

2. Patient has been treated with and failed at least one prior systemic gemcitabine and
platinum-based chemotherapy for the advanced disease

3. Must have documentation of radiographic progression of disease on prior systemic
therapy

4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO
criteria (2010) for brain tumors.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

6. Adequate organ function

Exclusion Criteria:

A patient will be excluded from this study if any of the following criteria are met:

1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus
homeostasis.

2. History and/or current evidence of clinically significant ectopic
mineralization/calcification.

3. History and/or current evidence of clinically significant retinal disorder confirmed
by retinal examination.

4. A serious illness or medical condition(s)

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Karim Benhadji, MD

Role: Study Director

Affiliation: Taiho Oncology, Inc.

Overall Contact

Name: Karim Benhadji, MD

Phone: 609-250-7336

Email: clinicaltrialinfo@taihooncology.com

LOCATION

Facility Status Contact
Facility: Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Status: Recruiting Contact:
Rachel Hungerford, RN
480-256-5423
BMDACCResearch@bannerhealth.com
Facility: Mayo Clinic (AZ)
Scottsdale, Arizona 85259
United States
Status: Recruiting Contact:
Brett Madden
480-342-4800
Madden.brett@mayo.edu
Facility: City of Hope National Medical Center
Duarte, California 91010
United States
Status: Recruiting Contact:
Daneng Li
626-471-9200
danli@coh.org
Facility: UCSF - Helen Diller
San Francisco, California 94158
United States
Status: Recruiting Contact:
Lillian Jahan
415-502-4174
lillian.jahan@ucsf.edu
Facility: Mayo Clinic (Jacksonville)
Jacksonville, Florida 32224
United States
Status: Recruiting Contact:
Evans Pope
904-953-3814
Pope.evans@mayo.edu
Facility: Florida Hospital
Orlando, Florida 32804
United States
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Cancer Treatment Centers of America
Newnan, Georgia 30265
United States
Status: Recruiting Contact:
Becky Slawik
770-400-7191
Becky.slawik@ctca-hope.com
Facility: Cancer Treatment Centers of America Zion, IL
Zion, Illinois 60099
United States
Status: Recruiting Contact:
Maria E Rivas
847-872-4019
maria.rivas@ctca-hope.com
Facility: The University of Kansas Cancer Center
Westwood, Kansas 66205
United States
Status: Recruiting Contact:
LaToya Berry
913-945-8871
lberry4@kumc.edu
Facility: Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Status: Recruiting Contact:
Patty Lynch
617-643-0815
lynch.patricia2@mgh.harvard.edu
Facility: Cancer Center at Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
United States
Status: Recruiting Contact:
Mary Linton Peters
617-667-2100
mbpeters@bidmc.harvard.edu
Facility: Dana Farber Cancer Institution
Boston, Massachusetts 02215
United States
Status: Recruiting Contact:
GI Clinical Research Line
617-632-5960
Facility: Wayne State Universtity (Karmanos Cancer Institute)
Detroit, Michigan 48201
United States
Status: Recruiting Contact:
Amanda Newman
313-576-8411
newmana@karmanos.org
Facility: Mayo Clinic (MN)
Rochester, Minnesota 55905
United States
Status: Recruiting Contact:
Toni Mangskau
507-538-3365
cancerctr@mayo.edu
Facility: New Mexico Cancer Care Alliance
Albuquerque, New Mexico 87106
United States
Status: Recruiting Contact:
Ursa Brown-Glaberman
505-272-4946
ubrown-glaberman@salud.unm.edu
Facility: Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Sidney Kimmel Cancer Center at Jefferson
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact:
Cynthia Perez
215-955-6407
Cynthia.Perez@jefferson.edu
Facility: Cancer Treatment Centers of America Philadelphia, PA
Philadelphia, Pennsylvania 19124
United States
Status: Recruiting Contact:
Paolo Casibang, RN
215-537-6438
ERMC@ctca-hope.com
Facility: University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15232
United States
Status: Recruiting Contact:
Kimberly Auth
412-623-5396
preastk@upmc.edu
Facility: Greenville Health System ITOR
Greenville, South Carolina 29605
United States
Status: Recruiting Contact:
Lisa Johnson
864-455-3600
Ljohnson4@ghs.org
Facility: Spartanburg Medical Center
Spartanburg, South Carolina 29303
United States
Status: Recruiting Contact:
Ken Kuenzli, RN
864-560-7579
kkuenzli@gibbscc.org
Facility: Mary Crowley
Dallas, Texas 75251
United States
Status: Recruiting Contact:
Mary Crowley Cancer Research
972-566-3000
Facility: MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact:
Funda Meric-Bernstam
713-792-3737
Fmeric@mdanderson.org
Facility: Virginia Mason Cancer Center
Seattle, Washington 98101
United States
Status: Recruiting Contact:
Ryan Sinit
206-341-8945
Ryan.Sinit@virginiamason.org
Facility: UW Carbone Cancer Center
Madison, Wisconsin 53792
United States
Status: Recruiting Contact:
Cancer Connect
608-262-5223
cancerconnect@uwhealth.org
Facility: Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Status: Recruiting Contact:
Medical College of Wisconsin Clinical Trials office
866-680-0505
_cccto@mcw.edu
Facility: Royal Melbourne Hospital
Melbourne,
Australia
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Scientia Clinical Research University of New South Wales
Randwick, 2031
Australia
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Scientia Clinical Research University of New South Wales
Randwick, NSW 2031
Australia
Status: Recruiting Contact:
Noman Bakhshi
+61 29382 5824
noman.bakhshi@scientiaclinicalresearch.com.au
Facility: Institut Bergonie
Bordeaux, 33000
France
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Hospices Civils de Lyon
Bron, 69677
France
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Centre Léon Bérard Bât
Lyon, 69008
France
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Pitié-Salpêtrière Hospital
Paris, 75013
France
Status: Recruiting Contact:
Marc Sanson
0033142160435
marc.sanson@aphp.fr
Facility: Institute Goustave-Roussy
Paris,
France
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Rennes, Centre Eugène Marquis
Rennes cedex, 35042
France
Status: Recruiting Contact:
Christelle Nicolle
+33 (0)2 99 25 32 64
c.nicolle@rennes.unicancer.fr
Facility: The Chinese University of Hong Kong
Sha Tin,
Hong Kong
Status: Recruiting Contact:
Dr. Stephen Lam Chan
(852) 35052166
l_chan@clo.cuhk.edu.hk
Facility: Prince of Wales Hospital
Shatin,
Hong Kong
Status: Recruiting Contact:
Dr. Stephen Lam Chan
(852) 35052166
chanlam_stephen@cuhk.edu.hk
Facility: Nagoya University Hospital
Nagoya, 466-8560
Japan
Status: Recruiting Contact:
Takashi Mizuno
+81 52744 2222
tmzn@med.nagoya-u.ac.jp
Facility: Osaka International Cancer Institute
Osaka, 541-8567
Japan
Status: Recruiting Contact:
Tatsuya Ioka
06 6945 1181
ioka_ta@hotmail.com
Facility: Yonsei University, Severance Hospital (Seoul)
Seoul, 03722
Korea, Republic of
Status: Recruiting Contact:
Hyun Jung Park
82-2-2228-8054
HJWWJD@yuhs.ac
Facility: ASAN Medical Center (Seoul)
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact:
Su-Young Kim
+82 2 3010 5634
sykim92@amc.seoul.kr
Facility: Samsung Medical Center (Seoul)
Seoul, 06351
Korea, Republic of
Status: Recruiting Contact:
Joon Oh Park, M.D., Ph.D
+82 2 3410 3459
oncopark@skku.edu
Facility: Seoul National University Hospital
Seoul, 110-744
Korea, Republic of
Status: Recruiting Contact:
Dr. Do-Youn Oh
+82 2 2072 0701
ohdoyoun@snu.ac.kr
Facility: University of Amsterdam
Amsterdam, 1105AZ
Netherlands
Status: Recruiting Contact:
HJ Klumpen
+31205665955
Secr-onco@amc.nl
Facility: Val D'Hebron University Hospital
Barcelona, 08035
Spain
Status: Recruiting Contact:
Ignacio Matos
34934894350
imatos@vhio.net
Facility: Hospital Clinic i Provincial de Barcelona,
Barcelona, 08036
Spain
Status: Recruiting Contact:
Dr Javier García-Corbacho
93 2279214
Garcia33@clinic.ub.es
Facility: University Hospital Ramón y Cajal
Madrid, 28034
Spain
Status: Recruiting Contact:
Federico Longo
+34913368263
federico.longo@salud.madrid.org
Facility: Centro Integral Oncológico Clara Campal - Hospital Universitario Madrid Sanchinarro
Madrid,
Spain
Status: Recruiting Contact:
Valentina Boni
+34 917567825
Valentina.Boni@start.stoh.com
Facility: National Taiwan University Hospital
Taipei, 10048
Taiwan
Status: Recruiting Contact:
Chih-Hung Hsu
+886 2 2312 3456
chihhunghsu@ntu.edu.tw
Facility: Guy's and St Thomas' NHS Foundation Trust
London, SE1 9RT
United Kingdom
Status: Recruiting Contact:
Dr. Debashis Sarker
+44 20 7188 8103
earlyphaseresearchteam@gstt.nhs.uk
Facility: University College London Hospital
London, W1T 7HA
United Kingdom
Status: Recruiting Contact:
Jerry Huang, MD
609-250-7208
jhuang@taihooncology.com
Facility: Sarah Cannon Research Institute
London,
United Kingdom
Status: Recruiting Contact:
Tobias Arkenau
0203 219 5200
Tobias.Arkenau@HCAHealthcare.co.uk