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

NCT03845166 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: XL092-0012020-003569-21
• Study Type: interventional
• Target: 325
• Locations: 10 countries
• Sites: 86

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Dose-Escalation Stage: MTD/recommended dose for XL092

  To determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for further evaluation of XL092 when administered alone and in combination with immune checkpoint inhibitors (ICIs) to subjects with advanced solid tumors

  Up to 24 months

• Cohort-Expansion Stage: Objective Response Rate (ORR)

  To evaluate preliminary efficacy of XL092 when administered alone and in combination with ICIs by estimating ORR as assessed by the Investigator per RECIST 1.1

  Up to 24 months

• Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)

  To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with ICIs for specific cohorts by estimating the percentage of subjects with PFS at 6 months (PFS rate) per RECIST 1.1 as assessed by the Investigator (except for the CRC expansion cohort H)

  Up to 24 months

• Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)

  To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with atezolizumab for subjects with RAS wild-type CRC (Cohort H Treatment Arms H-A and H-B) by estimating overall survival (OS)

  Up to 24 months

Secondary Outcomes (6)

• Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 36 months

• Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)

  Up to 24 months

• Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)

  Up to 24 months

• Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)

  Up to 24 months

• Dose-Escalation Stage: Terminal Half-Life

  Up to 24 months

Study Arms (5)

XL092 Single-Agent Dose-Escalation Cohorts

EXPERIMENTAL

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

Drug: XL092

XL092 Single-Agent Expansion Cohorts

EXPERIMENTAL

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).

Drug: XL092

XL092 + Atezolizumab Dose-Escalation Cohorts

EXPERIMENTAL

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

Drug: XL092; Drug: Atezolizumab

XL092 + Atezolizumab Expansion Cohorts

EXPERIMENTAL

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).

Drug: XL092; Drug: Atezolizumab

XL092 + Avelumab Dose-Escalation Cohorts

EXPERIMENTAL

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

Drug: XL092; Drug: Avelumab

Interventions

XL092 DRUG

oral doses of XL092

XL092 + Atezolizumab Dose-Escalation Cohorts; XL092 + Atezolizumab Expansion Cohorts; XL092 + Avelumab Dose-Escalation Cohorts; XL092 Single-Agent Dose-Escalation Cohorts; XL092 Single-Agent Expansion Cohorts

Atezolizumab DRUG

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

Also known as: Tecentriq®

XL092 + Atezolizumab Dose-Escalation Cohorts; XL092 + Atezolizumab Expansion Cohorts

Avelumab DRUG

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

Also known as: Bavencio®

XL092 + Avelumab Dose-Escalation Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (86)

Exelixis Clinical Site #6

Duarte, California, 91010, United States

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Exelixis Clinical Site #49

La Jolla, California, 92093, United States

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Exelixis Clinical Site #7

Los Angeles, California, 90025, United States

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Exelixis Clinical Site #84

Los Angeles, California, 90095, United States

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Exelixis Clinical Site #66

San Francisco, California, 94158, United States

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Exelixis Clinical Site #71

Stanford, California, 94305, United States

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Exelixis Clinical Site #15

Lake Mary, Florida, 32746, United States

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Exelixis Clinical Site #24

Miami, Florida, 33136, United States

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Exelixis Clinical Site #11

Atlanta, Georgia, 30322, United States

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Exelixis Clinical Site #80

Atlanta, Georgia, 30342, United States

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Exelixis Clinical Site #41

Iowa City, Iowa, 52242, United States

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Exelixis Clinical Site #36

Westwood, Kansas, 66205, United States

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Exelixis Clinical Site #62

Scarborough, Maine, 04074, United States

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Exelixis Clinical Site #44

Baltimore, Maryland, 21201, United States

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Exelixis Clinical Site #4

Boston, Massachusetts, 02215, United States

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Exelixis Clinical Site #45

Ann Arbor, Michigan, 48109, United States

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Exelixis Clinical Site #2

Grand Rapids, Michigan, 49546, United States

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Exelixis Clinical Site #25

Saint Paul, Minnesota, 55101, United States

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Exelixis Clinical Site #13

Omaha, Nebraska, 68130, United States

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Exelixis Clinical Site #9

East Brunswick, New Jersey, 08816, United States

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Exelixis Clinical Site #83

New Brunswick, New Jersey, 08903, United States

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Exelixis Clinical Site #86

New York, New York, 10021, United States

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Exelixis Clinical Site #35

New York, New York, 10029, United States

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Exelixis Clinical #78

New York, New York, 10065, United States

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Exelixis Clinical Site #85

The Bronx, New York, 10461, United States

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Exelixis Clinical #74

Cincinnati, Ohio, 45219, United States

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Exelixis Clinical Site #60

Cleveland, Ohio, 44106, United States

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Exelixis Clinical Site #59

Hershey, Pennsylvania, 17033, United States

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Exelixis Clinical Site #58

Philadelphia, Pennsylvania, 19107, United States

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Exelixis Clinical Site #12

Pittsburgh, Pennsylvania, 15232, United States

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Exelixis Clinical Site #61

Charleston, South Carolina, 29425, United States

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Exelixis Clinical Site #50

Myrtle Beach, South Carolina, 29572, United States

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Exelixis Clinical Site #33

Germantown, Tennessee, 38138, United States

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Exelixis Clinical Site #87

Nashville, Tennessee, 37203, United States

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Exelixis Clinical Site #3

Houston, Texas, 77030, United States

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Exelixis Clinical Site #1

San Antonio, Texas, 78229, United States

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Exelixis Clinical Site #5

Salt Lake City, Utah, 84112, United States

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Exelixis Clinical Site #8

Charlottesville, Virginia, 22903, United States

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Exelixis Clinical Site #43

Richmond, Virginia, 23219, United States

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Exelixis Clinical Site #26

Spokane, Washington, 99208, United States

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Exelixis Clinical Site #52

Darlinghurst, New South Wales, 2010, Australia

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Exelixis Clinical Site #53

Liverpool, New South Wales, 2170, Australia

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Exelixis Clinical #75

South Brisbane, Queensland, 4101, Australia

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Exelixis Clinical Site #56

Kurralta Park, South Australia, 5037, Australia

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Exelixis Clinical Site #63

Heidelberg, Victoria, 3084, Australia

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Exelixis Clinical Site #44

Edegem, Antwerpen, 2650, Belgium

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Exelixis Clinical Site #65

Ghent, Oost-Vlaanderen, 9000, Belgium

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Exelixis Clinical Site #51

Brussels, 1200, Belgium

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Exelixis Clinical Site #21

Brno, 656 91, Czechia

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Exelixis Clinical Site #42

Hradec Králové, 500 05, Czechia

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Exelixis Clinical Site #10

Olomouc, 779 00, Czechia

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Exelixis Clinical Site #27

Prague, 140 59, Czechia

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Exelixis Clinical Site #46

Clermont, Ferrand, 63011, France

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Exelixis Clinical Site #37

Saint-Herblain, Loire Atlantique, 44805, France

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Exelixis Clinical #72

Bordeaux, 33000, France

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Exelixis Clinical Site #32

Caen, 14076, France

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Exelixis Clinical Site #48

Marseille, 13009, France

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Exelixis Clinical Site #14

Paris, 75015, France

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Exelixis Clinical Site #39

Pierre-Bénite, 69495, France

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Exelixis Clinical Site #47

Poitiers, 86021, France

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Exelixis Clinical Site #22

Suresnes, 92150, France

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Exelixis Clinical Site #57

Toulouse, 31059, France

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Exelixis Clinical #77

Villejuif, 94805, France

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Exelixis Clinical Site #38

Nürtingen, Baden-Wurttemberg, 72622, Germany

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Exelixis Clinical Site #31

Münster, North Rhine-Westphalia, 48149, Germany

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Exelixis Clinical Site #64

Hamburg, 20249, Germany

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Exelixis Clinical Site #67

Milan, MI, 20132, Italy

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Exelixis Clinical Site #69

Pavia, PV, 27100, Italy

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Exelixis Clinical Site #54

Milan, 20141, Italy

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Exelixis Clinical #73

Napoli, 80131, Italy

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Exelixis Clinical Site #79

Amsterdam, North Holland, 1066 CX, Netherlands

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Exelixis Clinical #76

Rotterdam, South Holland, 3015 GD, Netherlands

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Exelixis Clinical Site #23

Sabadell, Barcelona, 08208, Spain

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Exelixis Clinical Site #20

Santiago de Compostela, La Coruna, 15706, Spain

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Exelixis Clinical Site #18

Barcelona, 08003, Spain

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Exelixis Clinical Site #19

Barcelona, 08023, Spain

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Exelixis Clinical Site #29

Barcelona, 08035, Spain

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Exelixis Clinical Site #30

Barcelona, 08036, Spain

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Exelixis Clinical Site #81

Madrid, 28007, Spain

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Exelixis Clinical Site #34

Madrid, 28040, Spain

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Exelixis Clinical Site #55

Madrid, 28041, Spain

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Exelixis Clinical Site #17

Madrid, 28046, Spain

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Exelixis Clinical Site #16

Seville, 41013, Spain

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Exelixis Clinical #70

London, England, W1G6AD, United Kingdom

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Exelixis Clinical Site #40

Sutton, England, SM2 5PT, United Kingdom

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Exelixis Clinical Site #68

Preston, Lancashire, PR29HT, United Kingdom

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MeSH Terms

Conditions

Neoplasms; Carcinoma, Renal Cell; Colorectal Neoplasms

Interventions

atezolizumab; avelumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: single-agent and combination therapy dose-escalation followed by cohort-expansion

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 19, 2019
• Study Start: March 20, 2019
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

BE (3); GB (3); CZ (4); US (40); IT (4); AU (5); DE (3); NL (2); FR (11); ES (11)