A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

NCT ID: NCT03845166

Last Updated: 2024-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

325 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-20

Study Completion Date

2027-05-31

Brief Summary

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This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers of XL092 administered alone, in combination with atezolizumab, and in combination with avelumab to subjects with advanced solid tumors.

Detailed Description

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Conditions

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Neoplasm Malignant Renal Cell Carcinoma Hormone Receptor Positive Breast Carcinoma Metastatic Castration-resistant Prostate Cancer Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

single-agent and combination therapy dose-escalation followed by cohort-expansion
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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XL092 Single-Agent Dose-Escalation Cohorts

Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

oral doses of XL092

XL092 Single-Agent Expansion Cohorts

The MTD or recommended dose from the dose-escalation stage may be further explored in clear cell renal cell carcinoma (ccRCC), non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), and metastatic castration-resistant prostate cancer (mCRPC).

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

oral doses of XL092

XL092 + Atezolizumab Dose-Escalation Cohorts

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

oral doses of XL092

Atezolizumab

Intervention Type DRUG

Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)

XL092 + Atezolizumab Expansion Cohorts

The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC).

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

oral doses of XL092

Atezolizumab

Intervention Type DRUG

Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)

XL092 + Avelumab Dose-Escalation Cohorts

Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

oral doses of XL092

Avelumab

Intervention Type DRUG

Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)

Interventions

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XL092

oral doses of XL092

Intervention Type DRUG

Atezolizumab

Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)

Intervention Type DRUG

Avelumab

Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)

Intervention Type DRUG

Other Intervention Names

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Tecentriq® Bavencio®

Eligibility Criteria

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Inclusion Criteria

* Cytologically or histologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent.
* Dose-escalation (single-agent and combination therapy): Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
* Expansion Cohort A (ccRCC): Subjects with previously treated advanced RCC with clear cell histology (including those with a sarcomatoid component) who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
* Expansion Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with non-clear cell histology who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
* Expansion Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor receptor 2 (HER-2) and who have radiographically progressed during or following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
* Expansion Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of the prostate). Neuroendocrine differentiation and other features permitted if adenocarcinoma is the primary histology.
* Expansion Cohort H (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum, KRAS/NRAS wild-type (confirmed via local testing report) and determined NOT to have microsatellite instability high (MSI-high) or mismatch repair deficient (dMMR) by local testing, who received the following standard of care chemotherapy regimens as prior therapy for metastatic CRC:

* Fluoropyrimidine, irinotecan and oxaliplatin, with or without an anti-VEGF monoclonal antibody (bevacizumab)
* Anti-EGFR monoclonal antibody (cetuximab or panitumumab)
* BRAF inhibitor (in combination with cetuximab +/- binimetinib) for subjects with BRAF V600E mutations
* Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1.
* Tumor tissue material:

* Subjects in the non-biomarker cohort provide archival, if available, or fresh tumor tissue if it can be safely obtained.
* Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
* Adequate organ and marrow function.
* Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
* Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria

* Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, and H only), or prior treatment with regorafenib and/or TAS-102 (Cohort H only).
* Receipt of any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.
* Receipt of any type of anticancer antibody, systemic chemotherapy, or hormonal anticancer therapy within 4 weeks before first dose of study treatment.
* Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
* Uncontrolled, significant intercurrent or recent illness.
* Concomitant use of certain medications.
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 450 ms for males and \> 470 ms for females. Single ECGs are no longer permitted.
* Pregnant or lactating females.
* Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.


* Diagnosis of immunodeficiency or is receiving systemic steroid therapy 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.


* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
* Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Exelixis Clinical Site #6

Duarte, California, United States

Site Status

Exelixis Clinical Site #49

La Jolla, California, United States

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Exelixis Clinical Site #7

Los Angeles, California, United States

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Exelixis Clinical Site #84

Los Angeles, California, United States

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Exelixis Clinical Site #66

San Francisco, California, United States

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Exelixis Clinical Site #71

Stanford, California, United States

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Exelixis Clinical Site #15

Lake Mary, Florida, United States

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Exelixis Clinical Site #24

Miami, Florida, United States

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Exelixis Clinical Site #11

Atlanta, Georgia, United States

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Exelixis Clinical Site #80

Atlanta, Georgia, United States

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Exelixis Clinical Site #41

Iowa City, Iowa, United States

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Exelixis Clinical Site #36

Westwood, Kansas, United States

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Exelixis Clinical Site #62

Scarborough, Maine, United States

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Exelixis Clinical Site #44

Baltimore, Maryland, United States

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Exelixis Clinical Site #4

Boston, Massachusetts, United States

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Exelixis Clinical Site #45

Ann Arbor, Michigan, United States

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Exelixis Clinical Site #2

Grand Rapids, Michigan, United States

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Exelixis Clinical Site #25

Saint Paul, Minnesota, United States

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Exelixis Clinical Site #13

Omaha, Nebraska, United States

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Exelixis Clinical Site #9

East Brunswick, New Jersey, United States

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Exelixis Clinical Site #83

New Brunswick, New Jersey, United States

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Exelixis Clinical Site #86

New York, New York, United States

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Exelixis Clinical Site #35

New York, New York, United States

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Exelixis Clinical #78

New York, New York, United States

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Exelixis Clinical Site #85

The Bronx, New York, United States

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Exelixis Clinical #74

Cincinnati, Ohio, United States

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Exelixis Clinical Site #60

Cleveland, Ohio, United States

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Exelixis Clinical Site #59

Hershey, Pennsylvania, United States

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Exelixis Clinical Site #58

Philadelphia, Pennsylvania, United States

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Exelixis Clinical Site #12

Pittsburgh, Pennsylvania, United States

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Exelixis Clinical Site #61

Charleston, South Carolina, United States

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Exelixis Clinical Site #50

Myrtle Beach, South Carolina, United States

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Exelixis Clinical Site #33

Germantown, Tennessee, United States

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Exelixis Clinical Site #87

Nashville, Tennessee, United States

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Exelixis Clinical Site #3

Houston, Texas, United States

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Exelixis Clinical Site #1

San Antonio, Texas, United States

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Exelixis Clinical Site #5

Salt Lake City, Utah, United States

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Exelixis Clinical Site #8

Charlottesville, Virginia, United States

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Exelixis Clinical Site #43

Richmond, Virginia, United States

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Exelixis Clinical Site #26

Spokane, Washington, United States

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Exelixis Clinical Site #52

Darlinghurst, New South Wales, Australia

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Exelixis Clinical Site #53

Liverpool, New South Wales, Australia

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Exelixis Clinical #75

South Brisbane, Queensland, Australia

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Exelixis Clinical Site #56

Kurralta Park, South Australia, Australia

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Exelixis Clinical Site #63

Heidelberg, Victoria, Australia

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Exelixis Clinical Site #44

Edegem, Antwerpen, Belgium

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Exelixis Clinical Site #65

Ghent, Oost-Vlaanderen, Belgium

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Exelixis Clinical Site #51

Brussels, , Belgium

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Exelixis Clinical Site #21

Brno, , Czechia

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Exelixis Clinical Site #42

Hradec Králové, , Czechia

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Exelixis Clinical Site #10

Olomouc, , Czechia

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Exelixis Clinical Site #27

Prague, , Czechia

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Exelixis Clinical Site #46

Clermont, Ferrand, France

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Exelixis Clinical Site #37

Saint-Herblain, Loire Atlantique, France

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Exelixis Clinical #72

Bordeaux, , France

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Exelixis Clinical Site #32

Caen, , France

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Exelixis Clinical Site #48

Marseille, , France

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Exelixis Clinical Site #14

Paris, , France

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Exelixis Clinical Site #39

Pierre-Bénite, , France

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Exelixis Clinical Site #47

Poitiers, , France

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Exelixis Clinical Site #22

Suresnes, , France

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Exelixis Clinical Site #57

Toulouse, , France

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Exelixis Clinical #77

Villejuif, , France

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Exelixis Clinical Site #38

Nürtingen, Baden-Wurttemberg, Germany

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Exelixis Clinical Site #31

Münster, North Rhine-Westphalia, Germany

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Exelixis Clinical Site #64

Hamburg, , Germany

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Exelixis Clinical Site #67

Milan, MI, Italy

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Exelixis Clinical Site #69

Pavia, PV, Italy

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Exelixis Clinical Site #54

Milan, , Italy

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Exelixis Clinical #73

Napoli, , Italy

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Exelixis Clinical Site #79

Amsterdam, North Holland, Netherlands

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Exelixis Clinical #76

Rotterdam, South Holland, Netherlands

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Exelixis Clinical Site #23

Sabadell, Barcelona, Spain

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Exelixis Clinical Site #20

Santiago de Compostela, La Coruna, Spain

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Exelixis Clinical Site #18

Barcelona, , Spain

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Exelixis Clinical Site #19

Barcelona, , Spain

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Exelixis Clinical Site #29

Barcelona, , Spain

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Exelixis Clinical Site #30

Barcelona, , Spain

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Exelixis Clinical Site #81

Madrid, , Spain

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Exelixis Clinical Site #34

Madrid, , Spain

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Exelixis Clinical Site #55

Madrid, , Spain

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Exelixis Clinical Site #17

Madrid, , Spain

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Exelixis Clinical Site #16

Seville, , Spain

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Exelixis Clinical #70

London, England, United Kingdom

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Exelixis Clinical Site #40

Sutton, England, United Kingdom

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Exelixis Clinical Site #68

Preston, Lancashire, United Kingdom

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Countries

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United States Australia Belgium Czechia France Germany Italy Netherlands Spain United Kingdom

Other Identifiers

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2020-003569-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

XL092-001

Identifier Type: -

Identifier Source: org_study_id

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