AzTrials
AzTrials

Urothelial CarcinomaPhase 1NCT03170960

Study of Cabozantinib Alone or in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors

A Phase 1 study testing cabozantinib and atezolizumab in people with Urothelial Carcinoma and Renal Cell Carcinoma, run by Exelixis at 124 sites in 9 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cabozantinib and atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
914 participants
Where
124 sitesin 9 countries
Study dates
5 Sep 2017to 30 Sep 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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).
Show all 9Show fewer
  • 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.

Trial locations and contacts

124 sites in 9 countries.

124 sites in 9 countries

United States57 sites

  • Exelixis Clinical Site #60

    Atlanta, Georgia, 30318

  • Exelixis Clinical Site #79

    Atlanta, Georgia, 30341

  • Exelixis Clinical Site #41

    Bethlehem, Pennsylvania, 18015

  • Exelixis Clinical Site #30

    Blacksburg, Virginia, 24060

  • Exelixis Clinical Site #65

    Bolivar, Missouri, 65613

  • Exelixis Clinical Site #10

    Boston, Massachusetts, 02215

  • Exelixis Clinical Site #38

    Camden, New Jersey, 08103

  • Exelixis Clinical Site #95

    Charleston, South Carolina, 29414

  • Exelixis Clinical Site #14

    Charlottesville, Virginia, 22908

  • Exelixis Clinical Site #67

    Cleveland, Ohio, 44195

  • Exelixis Clinical Site #49

    Columbus, Ohio, 43210

  • Exelixis Clinical Site #13

    Dallas, Texas, 75246

  • Exelixis Clinical Site #26

    Dallas, Texas, 75390

  • Exelixis Clinical Site #34

    Denver, Colorado, 80218

  • Exelixis Clinical Site #50

    Denver, Colorado, 80218

  • Exelixis Clinical Site #3

    Detroit, Michigan, 48201

  • Exelixis Clinical Site #1

    Duarte, California, 91010

  • Exelixis Clinical Site #27

    East Brunswick, New Jersey, 08816

  • Exelixis Clinical Site #40

    East Setauket, New York, 11733

  • Exelixis Clinical Site #23

    Fairway, Kansas, 66205

  • Exelixis Clinical Site #114

    Fort Worth, Texas, 76104

  • Exelixis Clinical Site #53

    Gilbert, Arizona, 85234

  • Exelixis Clinical Site #32

    Harvey, Illinois, 60426

  • Exelixis Clinical Site #29

    Houston, Texas, 77030

  • Exelixis Clinical Site #39

    Houston, Texas, 77030

  • Exelixis Clinical Site #44

    Houston, Texas, 77030

  • Exelixis Clinical Site #16

    Jacksonville, Florida, 32224

  • Exelixis Clinical Site #43

    Kansas City, Missouri, 64111

  • Exelixis Clinical Site #64

    Kettering, Ohio, 45409

  • Exelixis Clinical Site #20

    La Jolla, California, 92090

  • Exelixis Clinical Site #61

    Las Vegas, Nevada, 89169

  • Exelixis Clinical Site #57

    Lexington, Kentucky, 40536

  • Exelixis Clinical Site #46

    Los Angeles, California, 90025

  • Exelixis Clinical Site #33

    Lubbock, Texas, 79410

  • Exelixis Clinical Site #31

    New Brunswick, New Jersey, 08903

  • Exelixis Clinical Site #42

    New Haven, Connecticut, 06511

  • Exelixis Clinical Site #24

    New Orleans, Louisiana, 70112

  • Exelixis Clinical Site #11

    New York, New York, 10029

  • Exelixis Clinical Site #51

    Newport Beach, California, 92663

  • Exelixis Clinical Site #71

    Oklahoma City, Oklahoma, 73104

  • Exelixis Clinical Site #6

    Oklahoma City, Oklahoma, 73120

  • Exelixis Clinical Site #35

    Omaha, Nebraska, 68130

  • Exelixis Clinical Site #59

    Omaha, Nebraska, 68130

  • Exelixis Clinical Site #15

    Philadelphia, Pennsylvania, 19107

  • Exelixis Clinical Site #55

    Philadelphia, Pennsylvania, 19111

  • Exelixis Clinical Site #18

    Phoenix, Arizona, 85054

  • Exelixis Clinical Site #66

    Pittsburgh, Pennsylvania, 15232

  • Exelixis Clinical Site #102

    Portland, Oregon, 97213

  • Exelixis Clinical Site #45

    Portland, Oregon, 97239

  • Exelixis Clinical Site #17

    Rochester, Minnesota, 55905

  • Exelixis Clinical Site #2

    Salt Lake City, Utah, 84112

  • Exelixis Clinical Site #63

    San Antonio, Texas, 78229

  • Exelixis Clinical Site #62

    Santa Monica, California, 90404

  • Exelixis Clinical Site #21

    Stanford, California, 94305

  • Exelixis Clinical Site #76

    Tampa, Florida, 33612

  • Exelixis Clinical Site #37

    The Bronx, New York, 10461

  • Exelixis Clinical Site #48

    Washington D.C., District of Columbia, 20007

Other trials in United States

Spain24 sites

  • Exelixis Clinical Site #113

    Badalona, Barcelona, 08916

  • Exelixis Clinical Site #75

    Barcelona, 08003

  • Exelixis Clinical Site #58

    Barcelona, 08022

  • Exelixis Clinical Site #83

    Barcelona, 08023

  • Exelixis Clinical Site #86

    Barcelona, 08025

  • Exelixis Clinical Site #28

    Barcelona, 08035

  • Exelixis Clinical Site #9

    Barcelona, 08035

  • Exelixis Clinical Site #73

    Barcelona, 08036

  • Exelixis Clinical Site #91

    Elche, Alicante, 03203

  • Exelixis Clinical Site #118

    Girona, 17007

  • Exelixis Clinical Site #96

    Jeréz de La Frontera, Cádiz, 11407

  • Exelixis Clinical Site #77

    Madrid, 28034

  • Exelixis Clinical Site #106

    Madrid, 28040

  • Exelixis Clinical Site #111

    Madrid, 28040

  • Exelixis Clinical Site #22

    Madrid, 28041

  • Exelixis Clinical Site #5

    Madrid, 28041

  • Exelixis Clinical Site #81

    Madrid, 28046

  • Exelixis Clinical Site #100

    Málaga, 29010

  • Exelixis Clinical Site #94

    Oviedo, Principality of Asturias, 33011

  • Exelixis Clinical Site #70

    Palma de Mallorca, Balearic Islands, 07120 / 07010

  • Exelixis Clinical Site #90

    Pamplona, Navarre, 31008

  • Exelixis Clinical Site #116

    Sabadell, Barcelona, 08208

  • Exelixis Clinical Site #117

    San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320

  • Exelixis Clinical Site #74

    Santiago de Compostela, A Coruña, 15706

Other trials in Spain

France19 sites

  • Exelixis Clinical Site #92

    Bordeaux, 33076

  • Exelixis Clinical Site #93

    Brest, 29229

  • Exelixis Clinical Site #87

    Caen, 14076

  • Exelixis Clinical Site #88

    La Roche-sur-Yon, Cedex 9, 85925

  • Exelixis Clinical Site #69

    Le Mans, 72000

  • Exelixis Clinical Site #97

    Lille, 59000

  • Exelixis Clinical Site #89

    Lyon, 69373

  • Exelixis Clinical Site #109

    Marseille, 13273

  • Exelixis Clinical Site #104

    Nice, 06189

  • Exelixis Clinical Site #80

    Nîmes, 30029

  • Exelixis Clinical Site #78

    Paris, 75005

  • Exelixis Clinical Site #7

    Paris, 75010

  • Exelixis Clinical Site #68

    Paris, 75013

  • Exelixis Clinical Site #72

    Paris, 75015

  • Exelixis Clinical Site #82

    Saint-Grégoire, 35760

  • Exelixis Clinical Site #119

    Strasbourg, 67000

  • Exelixis Clinical Site #107

    Suresnes, 92150

  • Exelixis Clinical Site #105

    Vandœuvre-lès-Nancy, 54519

  • Exelixis Clinical Site #8

    Villejuif, Cedex, 94805

Other trials in France

Italy9 sites

  • Exelixis Clinical Site #84

    Meldola, FC, 47014

  • Exelixis Clinical Site #108

    Milan, 20132

  • Exelixis Clinical Site #103

    Milan, 20133

  • Exelixis Clinical Site #25

    Milan, 20133

  • Exelixis Clinical Site #4

    Milan, 20133

  • Exelixis Clinical Site #85

    Naples, 80131

  • Exelixis Clinical Site #121

    Pavia, 27100

  • Exelixis Clinical Site #110

    Roma, 00168

  • Exelixis Clinical Site #47

    Rozzano, Milano, 20089

Other trials in Italy

Australia6 sites

  • Exelixis Clinical Site #98

    Albury, New South Wales, 2640

  • Exelixis Clinical Site #101

    Camperdown, New South Wales, 2050

  • Exelixis Clinical Site #115

    Gosford, New South Wales, 2250

  • Exelixis Clinical Site #112

    North Ryde, New South Wales, 2109

  • Exelixis Clinical Site #123

    Randwick, New South Wales, 2031

  • Exelixis Clinical Site #99

    St Albans, Victoria, 3021

Other trials in Australia

United Kingdom4 sites

  • Exelixis Clinical Site #124

    Cardiff, Wales, CF14 2TL

  • Exelixis Clinical Site #19

    London, EC1M 6BQ

  • Exelixis Clinical Site #122

    Middlesex, England, HA6 2RN

  • Exelixis Clinical Site #120

    Preston, England, PR2 9HT

Other trials in United Kingdom

Belgium2 sites

  • Exelixis Clinical Site #52

    Ghent, 9000

  • Exelixis Clinical Site #54

    Leuven, 3000

Other trials in Belgium

Germany2 sites

  • Exelixis Clinical Site #56

    Düsseldorf, North Rhine-Westphalia, 40225

  • Exelixis Clinical Site #36

    Tübingen, 72076

Other trials in Germany

Netherlands1 site

  • Exelixis Clinical Site #12

    Nijmegen, Gelderland, 6525 GA

Other trials in Netherlands

About this study

Official title: 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

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.

Read the 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
Keywords
Kidney, Bladder, Renal pelvis, Ureter, Urethra, Cancer, Prostate, Castration-resistant, Lung, Breast, Ovarian, Endometrial, Liver, Stomach
Medical subject headings
Carcinoma, Transitional Cell, Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms, Carcinoma, Hepatocellular, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cabozantinibDrug

    Also called Cabometyx, XL184

    Supplied as 60-mg and 20-mg tablets; administered orally daily at dose levels of 20 mg, 40 mg, or 60 mg.

  • atezolizumabDrug

    Also called Tecentriq

    Supplied as 1200-mg vials; administered as an IV infusion once every 3 weeks (q3w).

  • cabozantinibDrug

    Also called Cabometyx, XL184

    Supplied as 60-mg and 20-mg tablets; administered orally daily at the Cohort Review Committee-determined recommended dose from the Dose Escalation Stage

  • cabozantinibDrug

    Also called Cabometyx, XL184

    Supplied as 60-mg and 20-mg tablets; administered orally daily at 60 mg qd

Study groups in NCT03170960
Study groupRoleWhat they receive
Dose EscalationExperimentalSubjects will accrue in cohorts of 3-6 subjects for evaluation of cabozantinib tablet dose of either 20 mg, 40 mg, and 60 mg orally qd in combination with standard dosing regimen of atezolizumab (1200 mg infusion q3w). A standard "3 plus 3" design will be utilized to determine a recommended combination dosing regimen for the Expansion Stage.
Receives: Drug: cabozantinib; Drug: atezolizumab
Expansion Cohort 1ExperimentalRCC subjects with clear cell histology who have not received prior systemic anticancer therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 2ExperimentalUC subjects (including bladder, renal pelvis, ureter, urethra) who have progressed on or after platinum-containing chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 3ExperimentalUC subjects (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 4ExperimentalUC subjects (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 5ExperimentalUC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (ICI) (anti-PD1 or anti-PD-L1) therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 6ExperimentalCRPC subjects who have radiographically progressed in soft tissue on or after enzalutamide and/or abiraterone acetate for metastatic disease.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 7ExperimentalStage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior immune checkpoint inhibitor (ICI) (anti-PD-1 or anti-PD-L1) therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 8ExperimentalStage IV non-squamous NSCLC subjects with positive PD-L1 expression and without prior systemic anticancer therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 9ExperimentalStage IV nonsquamous NSCLC subjects with sensitizing EGFR mutation who have radiographically progressed during or following prior treatment with an EGFR-targeting TKI. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 10ExperimentalRCC subjects with non-clear cell histology who have had up to one prior VEGFR-targeting TKI therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 11ExperimentalTNBC subjects who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 12ExperimentalOC subjects (including primary peritoneal cancer and fallopian tube cancer) who have platinum-resistant or refractory disease who have had up to two lines of prior systemic anticancer therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 13ExperimentalEC subjects (serous or endometrioid histology) who have radiographically progressed during or following treatment with at least one prior systemic anticancer therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 14ExperimentalHCC subjects (Child-Pugh score A) who have not received prior systemic anticancer therapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 15ExperimentalGC/GEJC/LEC subjects who have radiographically progressed during or following platinum-containing or fluoropyrimidine-containing chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 16ExperimentalCRC subjects who have radiographically progressed during or following systemic chemotherapy that contained fluoropyrimidine in combination with oxaliplatin or irinotecan.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 17ExperimentalH\&N cancer subjects who have radiographically progressed during or following prior platinum-containing chemotherapy. Prior treatment with ICIs (anti-PD1 or anti-PD-L1) is allowed if given in combination with chemotherapy.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 18ExperimentalDTC subjects (follicular, papillary, and poorly differentiated histologies) who are radioactive iodine (RAI) refractory or deemed ineligible for treatment with RAI.
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 19 (SAC)ExperimentalUC subjects (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.
Receives: Drug: cabozantinib
Expansion Cohort 20 (SAC)ExperimentalStage IV non-squamous NSCLC subjects who have radiographically progressed on or after treatment with one prior ICI (anti-PD-1 or anti-PD-L1). Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.
Receives: Drug: cabozantinib
Expansion Cohort 21 (SAC)ExperimentalMetastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.
Receives: Drug: cabozantinib
Expansion Cohort 22 (SAA)ExperimentalMetastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC. Subjects may be allowed to receive combination therapy at the Cohort Review Committee recommended dose following radiographic disease progression.
Receives: Drug: atezolizumab
Expansion Cohort 23ExperimentalMetastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with one, and only one, novel hormonal therapy (NHT) (eg, abiraterone, enzalutamide, apalutamide, daralutamide) for CSPC, mCRPC, or non-metastatic CRPC
Receives: Drug: atezolizumab; Drug: cabozantinib
Expansion Cohort 24ExperimentalMetastatic CRPC (mCRPC) subjects who have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features who have had prior treatment with at least one NHT and have received docetaxel for mCRPC
Receives: Drug: atezolizumab; Drug: cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation: MTD/Recommended Dose

    To determine the maximum tolerated dose (MTD) and/or recommended dose and schedule for the subsequent Expansion Stage of daily oral administration of cabozantinib in subjects with solid tumors when taken in combination with atezolizumab.

    Measured: Up to Day 21

  2. Dose Expansion: ORR

    To evaluate preliminary efficacy by estimating the Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1.

    Measured: Up to a maximum of 59 months

Secondary outcomes (1)

  1. Incidence and severity of nonserious AEs and SAEs (Safety)

    To assess safety for the combination therapy through the evaluation of incidence and severity of nonserious adverse events (AEs) and serious adverse events (SAEs), including immune-related adverse events (irAEs) and adverse events of special interest (AESIs).

    Measured: From first dose to 30 days following last dose (up to a maximum of 59 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2017
  2. Study start5 Sep 2017
  3. Primary completion21 Feb 2023
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose Escalation followed by Dose Expansion
Masking
None (open label)
Enrolment
914 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03170960
Sponsor's protocol ID
XL184-021
Status last verified
Sep 2026
First submitted
23 May 2017
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Pal SK, Loriot Y, Necchi A, Singh P, Castellano D, Pagliaro L, Suarez C, McGregor BA, Vaishampayan UN, Hauke RJ, Powles T, Van Herpen CML, Courtney KD, Dreicer R, Sudhagoni R, Schwickart M, Andrianova S, Agarwal N. COSMIC-021 Phase Ib Study of Cabozantinib Plus Atezolizumab: Results from the Locally Advanced or Metastatic Urothelial Carcinoma Cohorts. J Clin Oncol. 2025 May 10;43(14):1650-1662. doi: 10.1200/JCO-24-01675. Epub 2025 Feb 18.

    PubMed 39965176

  • Li D, Loriot Y, Burgoyne AM, Cleary JM, Santoro A, Lin D, Aix SP, Garrido-Laguna I, Sudhagoni R, Guo X, Andrianova S, Paulson S. Cabozantinib plus atezolizumab in previously untreated advanced hepatocellular carcinoma and previously treated gastric cancer and gastroesophageal junction adenocarcinoma: results from two expansion cohorts of a multicentre, open-label, phase 1b trial (COSMIC-021). EClinicalMedicine. 2023 Dec 21;67:102376. doi: 10.1016/j.eclinm.2023.102376. eCollection 2024 Jan.

    PubMed 38204489

  • Agarwal N, McGregor B, Maughan BL, Dorff TB, Kelly W, Fang B, McKay RR, Singh P, Pagliaro L, Dreicer R, Srinivas S, Loriot Y, Vaishampayan U, Goel S, Curran D, Panneerselvam A, Schwickart M, Choueiri TK, Pal S. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Lancet Oncol. 2022 Jul;23(7):899-909. doi: 10.1016/S1470-2045(22)00278-9. Epub 2022 Jun 9.

    PubMed 35690072

  • Pal SK, McGregor B, Suarez C, Tsao CK, Kelly W, Vaishampayan U, Pagliaro L, Maughan BL, Loriot Y, Castellano D, Srinivas S, McKay RR, Dreicer R, Hutson T, Dubey S, Werneke S, Panneerselvam A, Curran D, Scheffold C, Choueiri TK, Agarwal N. Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study. J Clin Oncol. 2021 Nov 20;39(33):3725-3736. doi: 10.1200/JCO.21.00939. Epub 2021 Sep 7.

    PubMed 34491815

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cabozantinib and atezolizumab in people with Urothelial Carcinoma and Renal Cell Carcinoma, run by Exelixis at 124 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 124 sites in United States, Spain, France, Italy, Australia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: MTD/Recommended Dose (time frame: Up to Day 21). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03170960, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

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