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Brief Title: XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

INTRODUCTION

  • Org Study ID: XL092-001
  • Secondary ID: 2020-003569-21
  • NTC ID: NCT03845166
  • Sponsor: Exelixis

BRIEF SUMMARY

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.

  • Overall Status
    Recruiting
  • Start Date
    March 20, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose-Escalation Stage: MTD/recommended dose for XL092

Primary Outcome 1 - Timeframe: Up to 24 months

Primary Outcome 2 - Measure: Cohort-Expansion Stage: Objective Response Rate (ORR)

Primary Outcome 2 - Timeframe: Up to 24 months

Primary Outcome 3 - Measure: Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)

Primary Outcome 3 - Timeframe: Up to 24 months

Primary Outcome 4 - Measure: Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)

Primary Outcome 4 - Timeframe: Up to 24 months

CONDITION

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

ELIGIBILITY

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 Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who received first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin.

- Expansion Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy.

- Expansion Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy.

- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1, with exception of Cohort I (UC, Maintenance Therapy).
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, H, I, and K only), prior treatment with avelumab (Cohort J 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.
Additional Exclusion Criteria for XL092 + Atezolizumab Combination Therapy Cohorts ONLY:
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.
Additional Exclusion Criteria for XL092 + Avelumab Combination Therapy Cohorts ONLY:
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.

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 #6
Duarte, California 91010
United States
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Facility: Exelixis Clinical Site #49
La Jolla, California 92093
United States
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Facility: Exelixis Clinical Site #7
Los Angeles, California 90025
United States
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Facility: Exelixis Clinical #71
Palo Alto, California 94304
United States
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Facility: Exelixis Clinical Site #66
San Francisco, California 94158
United States
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Facility: Exelixis Clinical #79
Santa Monica, California 90404
United States
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Facility: Exelixis Clinical Site #15
Lake Mary, Florida 32746
United States
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Facility: Exelixis Clinical Site #24
Miami, Florida 33136
United States
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Facility: Exelixis Clinical Site #41
Iowa City, Iowa 52242
United States
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Facility: Exelixis Clinical Site #36
Westwood, Kansas 66205
United States
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Facility: Exelixis Clinical Site #62
Scarborough, Maine 04074
United States
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Facility: Exelixis Clinical Site #44
Baltimore, Maryland 21201
United States
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Facility: Exelixis Clinical Site #4
Boston, Massachusetts 02215
United States
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Facility: Exelixis Clinical Site #45
Ann Arbor, Michigan 48109
United States
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Facility: Exelixis Clinical Site #2
Grand Rapids, Michigan 49546
United States
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Facility: Exelixis Clinical Site #13
Omaha, Nebraska 68130
United States
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Facility: Exelixis Clinical Site #9
East Brunswick, New Jersey 08816
United States
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Facility: Exelixis Clinical Site #35
New York, New York 10029
United States
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Facility: Exelixis Clinical #78
New York, New York 10065
United States
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Facility: Exelixis Clinical #74
Cincinnati, Ohio 45219
United States
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Facility: Exelixis Clinical Site #60
Cleveland, Ohio 44106
United States
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Facility: Exelixis Clinical Site #59
Hershey, Pennsylvania 17033
United States
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Facility: Exelixis Clinical Site #58
Philadelphia, Pennsylvania 19107
United States
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Facility: Exelixis Clinical Site #12
Pittsburgh, Pennsylvania 15232
United States
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Facility: Exelixis Clinical Site #61
Charleston, South Carolina 29425
United States
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Facility: Exelixis Clinical Site #50
Myrtle Beach, South Carolina 29572
United States
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Facility: Exelixis Clinical Site #33
Germantown, Tennessee 38138
United States
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Facility: Exelixis Clinical Site #3
Houston, Texas 77030
United States
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Facility: Exelixis Clinical Site #1
San Antonio, Texas 78229
United States
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Facility: Exelixis Clinical Site #5
Salt Lake City, Utah 84112
United States
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Facility: Exelixis Clinical Site #8
Charlottesville, Virginia 22903
United States
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Facility: Exelixis Clinical Site #43
Richmond, Virginia 23219
United States
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Facility: Exelixis Clinical Site #26
Spokane, Washington 99208
United States
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Facility: Exelixis Clinical Site #52
Darlinghurst, New South Wales 2010
Australia
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Facility: Exelixis Clinical Site #53
Liverpool, New South Wales 2170
Australia
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Facility: Exelixis Clinical #75
South Brisbane, Queensland 4101
Australia
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Facility: Exelixis Clinical Site #56
Kurralta Park, South Australia 5037
Australia
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Heidelberg, Victoria 3084
Australia
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Facility: Exelixis Clinical Site #44
Edegem, Antwerpen 2650
Belgium
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Facility: Exelixis Clinical Site #51
Bruxelles, Brussels 1200
Belgium
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Facility: Exelixis Clinical Site #65
Gent, Oost-Vlaanderen 9000
Belgium
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Facility: Exelixis Clinical Site #21
Brno, Ferrand 656 91
Czechia
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #42
Hradec Králové, Loire Atlantique 500 05
Czechia
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Facility: Exelixis Clinical Site #10
Olomouc, Baden-Wuerttemberg 779 00
Czechia
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Facility: Exelixis Clinical Site #27
Praha, Bavaria 140 59
Czechia
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Facility: Exelixis Clinical Site #46
Clermont, North Rhine-Westphalia 63011
France
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Facility: Exelixis Clinical Site #37
Saint-Herblain Cedex, MI 44805
France
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Facility: Exelixis Clinical #72
Bordeaux, PV 33076
France
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Facility: Exelixis Clinical Site #32
Caen Cedex 5, South Holland 14076
France
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Facility: Exelixis Clinical Site #48
Marseille, Barcelona 13009
France
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Paris, La Coruna 75015
France
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Facility: Exelixis Clinical Site #39
Pierre-Bénite, England 69310
France
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Facility: Exelixis Clinical Site #47
Poitiers, England 86000
France
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Facility: Exelixis Clinical Site #22
Suresnes, Lancashire 92150
France
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Facility: Exelixis Clinical Site #57
Toulouse Cedex 9, 31059
France
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Facility: Exelixis Clinical #77
Villejuif, 94805
France
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Facility: Exelixis Clinical Site #38
Nürtingen, 72622
Germany
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Facility: Exelixis Clinical Site #28
München, 81675
Germany
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Facility: Exelixis Clinical Site #31
Münster, 48149
Germany
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Facility: Exelixis Clinical Site #64
Hamburg, 20249
Germany
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Facility: Exelixis Clinical Site #67
Milano, 20132
Italy
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Facility: Exelixis Clinical Site #69
Pavia, 27100
Italy
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Facility: Exelixis Clinical Site #54
Milan, 20141
Italy
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Facility: Exelixis Clinical #73
Napoli, 80131
Italy
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Facility: Exelixis Clinical #76
Rotterdam, 3015 GD
Netherlands
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Facility: Exelixis Clinical Site #23
Sabadell, 08208
Spain
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Facility: Exelixis Clinical Site #20
Santiago De Compostela, 15706
Spain
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Facility: Exelixis Clinical Site #18
Barcelona, 08003
Spain
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Facility: Exelixis Clinical Site #19
Barcelona, 08023
Spain
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Facility: Exelixis Clinical Site #29
Barcelona, 08035
Spain
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Facility: Exelixis Clinical Site #30
Barcelona, 08036
Spain
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Facility: Exelixis Clinical Site #34
Madrid, 28040
Spain
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Facility: Exelixis Clinical Site #55
Madrid, 28041
Spain
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Facility: Exelixis Clinical Site #17
Madrid, 28046
Spain
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Facility: Exelixis Clinical Site #16
Sevilla, 41013
Spain
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Facility: Exelixis Clinical #70
London, W1G6AD
United Kingdom
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Facility: Exelixis Clinical Site #40
Sutton, SM2 5PT
United Kingdom
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Facility: Exelixis Clinical Site #68
Preston, PR29HT
United Kingdom
Status: Recruiting Contact: N/A