Atezolizumab: Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)
Avelumab: Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
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.
Primary outcome measure(s)
Dose-Escalation Stage: MTD/recommended dose for XL092 — Up to 24 months 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
Cohort-Expansion Stage: Objective Response Rate (ORR) — Up to 24 months 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
Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS) — Up to 24 months 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)
Cohort-Expansion Stage (Cohort H only): Overall Survival (OS) — Up to 24 months 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)
Trial sites (86)
Facility
City
Region
Status
Exelixis Clinical Site #6
Duarte
California
Exelixis Clinical Site #49
La Jolla
California
Exelixis Clinical Site #7
Los Angeles
California
Exelixis Clinical Site #84
Los Angeles
California
Exelixis Clinical Site #66
San Francisco
California
Exelixis Clinical Site #71
Stanford
California
Exelixis Clinical Site #15
Lake Mary
Florida
Exelixis Clinical Site #24
Miami
Florida
Exelixis Clinical Site #11
Atlanta
Georgia
Exelixis Clinical Site #80
Atlanta
Georgia
Exelixis Clinical Site #41
Iowa City
Iowa
Exelixis Clinical Site #36
Westwood
Kansas
Exelixis Clinical Site #62
Scarborough
Maine
Exelixis Clinical Site #44
Baltimore
Maryland
Exelixis Clinical Site #4
Boston
Massachusetts
Exelixis Clinical Site #45
Ann Arbor
Michigan
Exelixis Clinical Site #2
Grand Rapids
Michigan
Exelixis Clinical Site #25
Saint Paul
Minnesota
Exelixis Clinical Site #13
Omaha
Nebraska
Exelixis Clinical Site #9
East Brunswick
New Jersey
Exelixis Clinical Site #83
New Brunswick
New Jersey
Exelixis Clinical Site #86
New York
New York
Exelixis Clinical Site #35
New York
New York
Exelixis Clinical #78
New York
New York
Exelixis Clinical Site #85
The Bronx
New York
Exelixis Clinical #74
Cincinnati
Ohio
Exelixis Clinical Site #60
Cleveland
Ohio
Exelixis Clinical Site #59
Hershey
Pennsylvania
Exelixis Clinical Site #58
Philadelphia
Pennsylvania
Exelixis Clinical Site #12
Pittsburgh
Pennsylvania
Exelixis Clinical Site #61
Charleston
South Carolina
Exelixis Clinical Site #50
Myrtle Beach
South Carolina
Exelixis Clinical Site #33
Germantown
Tennessee
Exelixis Clinical Site #87
Nashville
Tennessee
Exelixis Clinical Site #3
Houston
Texas
Exelixis Clinical Site #1
San Antonio
Texas
Exelixis Clinical Site #5
Salt Lake City
Utah
Exelixis Clinical Site #8
Charlottesville
Virginia
Exelixis Clinical Site #43
Richmond
Virginia
Exelixis Clinical Site #26
Spokane
Washington
+ 46 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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