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Brief Title: Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

A Phase 1b Dose-Escalation Study of Cabozantinib (XL184) Administered Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

INTRODUCTION

  • Org Study ID: XL184-021
  • Secondary ID: N/A
  • NTC ID: NCT03170960
  • Sponsor: Exelixis

BRIEF SUMMARY

This is a multicenter Phase 1b, open-label study to assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of cabozantinib taken in combination with atezolizumab in subjects with multiple tumor types, including advanced urothelial carcinoma (UC) (including bladder, renal pelvis, ureter, urethra), renal cell carcinoma (RCC), castration-resistant prostate cancer (CRPC), non-small-cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer (OC), endometrial cancer (EC), hepatocellular cancer (HCC), gastric cancer/gastroesophageal junction cancer/lower esophageal cancer (GC/GEJC/LEC), colorectal cancer (CRC), head and neck (H&N) cancer, and differentiated thyroid cancer (DTC). The study consists of two stages: in the Dose Escalation Stage, an appropriate recommended cabozantinib dose for the combination with standard dosing regimen of atezolizumab will be established; in the Expansion Stage, tumor-specific cohorts will be enrolled in order to further evaluate the safety and efficacy of the combination treatment in these tumor indications. Three exploratory single-agent cabozantinib (SAC) cohorts may also be enrolled with UC, NSCLC, or CRPC subjects. One exploratory single-agent atezolizumab (SAA) cohort may also be enrolled with CRPC subjects. Subjects enrolled in the SAC cohorts and SAA cohort may receive combination treatment with both cabozantinib and atezolizumab after they experience radiographic progressive disease per the Investigator per RECIST 1.1. Due to the nature of this study design, some tumor cohorts may complete enrollment earlier than others.

DETAILED DESCRIPTION

Dose Escalation Stage: to determine the schedule and maximum tolerated dose (MTD) and/or recommended Expansion Stage dose of cabozantinib when taken in combination with a standard dosing regimen of atezolizumab (1200 mg infusion, once every 3 weeks).
Expansion Stage: to determine the preliminary efficacy (objective response rate [ORR] per RECIST 1.1) and safety of the recommended combination dose of cabozantinib with atezolizumab in eighteen tumor-specific cohorts including subjects with advanced UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N, and DTC.
Exploratory SAC Cohorts: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent cabozantinib in UC, NSCLC, and CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy
Exploratory SAA Cohort: Descriptive efficacy, safety, PK, and biomarker analyses of single-agent atezolizumab in CRPC subjects. Descriptive efficacy and safety analyses of combination therapy after progression on single-agent therapy

  • Overall Status
    Recruiting
  • Start Date
    September 5, 2017
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose Escalation: MTD/Recommended Dose

Primary Outcome 1 - Timeframe: Up to 6 months

Primary Outcome 2 - Measure: Dose Expansion: ORR

Primary Outcome 2 - Timeframe: Up to 31 months

CONDITION

  • Urothelial Carcinoma
  • Renal Cell Carcinoma
  • Non-Small Cell Lung Cancer
  • Castration-resistant Prostate Cancer
  • Triple Negative Breast Cancer
  • Ovarian Cancer
  • Endometrial Cancer
  • Hepatocellular Carcinoma
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • Colorectal Cancer
  • Head and Neck Cancer
  • Differentiated Thyroid Cancer
  • Lower Esophageal Cancer

ELIGIBILITY

Inclusion Criteria:
Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent:
Dose-Escalation Stage:
Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or

- Subjects with RCC (clear cell, non-clear cell histology) with or without prior systemic anticancer therapy
Expansion Stage:
Inoperable locally advanced or metastatic solid tumor (UC, RCC, CRPC, NSCLC, TNBC, OC, EC, HCC, GC/GEJC/LEC, CRC, H&N cancer, and DTC as outlined above)

- Measurable disease per RECIST 1.1 as determined by the investigator.

- Tumor tissue material available (archival or recent tumor biopsy)

- Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

- Age eighteen years or older on the day of consent.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

- Adequate organ and marrow function.

- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.

- Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
Prior treatment with cabozantinib or immune checkpoint inhibitors including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy except in Expansion Cohorts 5, 7, 9, 11, 17, 19 and 20. Other restrictions regarding prior therapy may apply.

- Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks before first dose of study treatment.

- Concomitant anticoagulation with oral anticoagulants.

- Subject is receiving systemic steroid therapy (>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.

- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.

- The subject has uncontrolled, significant intercurrent or recent illness, including, but not limited to, an active or history of autoimmune disease or immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia, pneumonitis; active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic hepatitis B or C infection, positive test for tuberculosis, moderate to severe hepatic impairment (Child-Pugh B or C).

- Pregnant or lactating females.

- Previously identified allergy or hypersensitivity to components of the study treatment formulations.

- Diagnosis of another malignancy within 2 years before first dose of study treatment.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 1-888-EXELIXIS (888-393-5494), 650-837-7400

Email: druginfo@exelixis.com

LOCATION

Facility Status Contact
Facility: Exelixis Clinical Site #53
Gilbert, Arizona 85234
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #18
Phoenix, Arizona 85054
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #1
Duarte, California 91010
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #20
La Jolla, California 92090
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #46
Los Angeles, California 90025
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #51
Newport Beach, California 92663
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #62
Santa Monica, California 90404
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #21
Stanford, California 94305
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #34
Denver, Colorado 80218
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #50
Denver, Colorado 80218
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #42
New Haven, Connecticut 06511
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #48
Washington, District of Columbia 20007
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #16
Jacksonville, Florida 32224
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #76
Tampa, Florida 33612
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #60
Atlanta, Georgia 30318
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #79
Atlanta, Georgia 30341
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #32
Harvey, Illinois 60426
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #23
Fairway, Kansas 66205
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #57
Lexington, Kentucky 40536
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #24
New Orleans, Louisiana 70112
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #10
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #3
Detroit, Michigan 48201
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #17
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #65
Bolivar, Missouri 65613
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #43
Kansas City, Missouri 64111
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #35
Omaha, Nebraska 68130
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #59
Omaha, Nebraska 68130
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #61
Las Vegas, Nevada 89169
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #38
Camden, New Jersey 08103
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #27
East Brunswick, New Jersey 08816
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #31
New Brunswick, New Jersey 08903
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #37
Bronx, New York 10461
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #40
East Setauket, New York 11733
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #11
New York, New York 10029
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #67
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #49
Columbus, Ohio 43210
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #64
Kettering, Ohio 45409
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #71
Oklahoma City, Oklahoma 73104
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #6
Oklahoma City, Oklahoma 73120
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #102
Portland, Oregon 97213
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #45
Portland, Oregon 97239
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #41
Bethlehem, Pennsylvania 18015
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #15
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #55
Philadelphia, Pennsylvania 19111
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #66
Pittsburgh, Pennsylvania 15232
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #95
Charleston, South Carolina 29414
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #13
Dallas, Texas 75246
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #26
Dallas, Texas 75390
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #114
Fort Worth, Texas 76104
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #29
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #39
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #44
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #33
Lubbock, Texas 79410
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #63
San Antonio, Texas 78229
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #2
Salt Lake City, Utah 84112
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #30
Blacksburg, Virginia 24060
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #14
Charlottesville, Virginia 22908
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #98
Albury, New South Wales 2640
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #101
Camperdown, New South Wales 2050
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #115
Gosford, New South Wales 2250
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #112
North Ryde, New South Wales 2109
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #123
Randwick, New South Wales 2031
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #99
St Albans, Victoria 3021
Australia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #52
Gent, Cedex 9 9000
Belgium
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #54
Leuven, Cedex 3000
Belgium
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #88
La Roche-sur-Yon, Nordrhein-Westfalen 85925
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #8
Villejuif, FC 94805
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #92
Bordeaux, Milano 33076
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #93
Brest, Gelderland 29229
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #87
CAEN Cedex 05, A Coruña 14076
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #69
Le Mans, Alicante 72000
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #97
Lille, Asturias 59000
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #89
Lyon Cedex 08, Baleares 69373
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #109
Marseille, Barcelona 13273
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #104
Nice Cedex 02, Barcelona 06189
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #80
Nîmes Cedex 09, Cádiz 30029
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #78
Paris, Navarra 75005
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #7
Paris, Santa Cruz De Tenerife 75010
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #68
Paris, England 75013
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #72
Paris, England 75015
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #82
Saint-Grégoire, Wales 35760
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #119
Strasbourg, 67000
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #107
Suresnes, 92150
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #105
Vandoeuvre les nancy, 54519
France
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #56
Düsseldorf, 40225
Germany
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #36
Tübingen, 72076
Germany
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #84
Meldola, 47014
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #47
Rozzano, 20089
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #108
Milano, 20132
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #103
Milano, 20133
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #25
Milano, 20133
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #4
Milano, 20133
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #85
Napoli, 80131
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #121
Pavia, 27100
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #110
Roma, 00168
Italy
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #12
Nijmegen, 6525 GA
Netherlands
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #74
Santiago De Compostela, 15706
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #91
Elche, 03203
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #94
Oviedo, 33011
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #70
Palma De Mallorca, 07120 / 07010
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #113
Badalona, 08916
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #116
Sabadell, 08208
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #96
Jeréz De La Frontera, 11407
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #90
Pamplona, 31008
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #117
La Laguna, 38320
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #75
Barcelona, 08003
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #58
Barcelona, 08022
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #83
Barcelona, 08023
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #86
Barcelona, 08025
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #28
Barcelona, 08035
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #9
Barcelona, 08035
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #73
Barcelona, 08036
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #118
Girona, 17007
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #77
Madrid, 28034
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #106
Madrid, 28040
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #111
Madrid, 28040
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #22
Madrid, 28041
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #5
Madrid, 28041
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #81
Madrid, 28046
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #100
Málaga, 29010
Spain
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #122
Middlesex, HA6 2RN
United Kingdom
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #120
Preston, PR2 9HT
United Kingdom
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #124
Cardiff, CF14 2TL
United Kingdom
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #19
London, EC1M 6BQ
United Kingdom
Status: Recruiting Contact: N/A