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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03845166




Registration number
NCT03845166
Ethics application status
Date submitted
15/02/2019
Date registered
19/02/2019
Date last updated
20/02/2024

Titles & IDs
Public title
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors
Scientific title
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
Secondary ID [1] 0 0
2020-003569-21
Secondary ID [2] 0 0
XL092-001
Universal Trial Number (UTN)
Trial acronym
STELLAR-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasm Malignant 0 0
Renal Cell Carcinoma 0 0
Hormone Receptor Positive Breast Carcinoma 0 0
Metastatic Castration-resistant Prostate Cancer 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - XL092
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Avelumab

Experimental: XL092 Single-Agent Dose-Escalation Cohorts - Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.

Experimental: 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).

Experimental: XL092 + Atezolizumab Dose-Escalation Cohorts - Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.

Experimental: 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).

Experimental: XL092 + Avelumab Dose-Escalation Cohorts - Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.


Treatment: Drugs: XL092
oral doses of XL092

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

Treatment: Drugs: Avelumab
Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Escalation Stage: MTD/recommended dose for XL092
Timepoint [1] 0 0
Up to 24 months
Primary outcome [2] 0 0
Cohort-Expansion Stage: Objective Response Rate (ORR)
Timepoint [2] 0 0
Up to 24 months
Primary outcome [3] 0 0
Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS)
Timepoint [3] 0 0
Up to 24 months
Primary outcome [4] 0 0
Cohort-Expansion Stage (Cohort H only): Overall Survival (OS)
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Dose-Escalation Stage: Terminal Half-Life
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Dose-Escalation Stage: Apparent Clearance (CL/F)
Timepoint [6] 0 0
Up to 24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2024
Actual
Sample size
Target
Accrual to date
Final
325
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Exelixis Clinical Site #52 - Darlinghurst
Recruitment hospital [2] 0 0
Exelixis Clinical Site #53 - Liverpool
Recruitment hospital [3] 0 0
Exelixis Clinical #75 - South Brisbane
Recruitment hospital [4] 0 0
Exelixis Clinical Site #56 - Kurralta Park
Recruitment hospital [5] 0 0
Exelixis Clinical Site #63 - Heidelberg
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Maine
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Belgium
State/province [22] 0 0
Antwerpen
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Oost-Vlaanderen
Country [25] 0 0
Czechia
State/province [25] 0 0
Brno
Country [26] 0 0
Czechia
State/province [26] 0 0
Hradec Králové
Country [27] 0 0
Czechia
State/province [27] 0 0
Olomouc
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha
Country [29] 0 0
France
State/province [29] 0 0
Ferrand
Country [30] 0 0
France
State/province [30] 0 0
Loire Atlantique
Country [31] 0 0
France
State/province [31] 0 0
Bordeaux
Country [32] 0 0
France
State/province [32] 0 0
Caen Cedex 5
Country [33] 0 0
France
State/province [33] 0 0
Marseille
Country [34] 0 0
France
State/province [34] 0 0
Paris
Country [35] 0 0
France
State/province [35] 0 0
Pierre-Bénite
Country [36] 0 0
France
State/province [36] 0 0
Poitiers
Country [37] 0 0
France
State/province [37] 0 0
Suresnes
Country [38] 0 0
France
State/province [38] 0 0
Toulouse Cedex 9
Country [39] 0 0
France
State/province [39] 0 0
Villejuif
Country [40] 0 0
Germany
State/province [40] 0 0
Baden-Wuerttemberg
Country [41] 0 0
Germany
State/province [41] 0 0
Bavaria
Country [42] 0 0
Germany
State/province [42] 0 0
North Rhine-Westphalia
Country [43] 0 0
Germany
State/province [43] 0 0
Hamburg
Country [44] 0 0
Italy
State/province [44] 0 0
MI
Country [45] 0 0
Italy
State/province [45] 0 0
PV
Country [46] 0 0
Italy
State/province [46] 0 0
Milan
Country [47] 0 0
Italy
State/province [47] 0 0
Napoli
Country [48] 0 0
Netherlands
State/province [48] 0 0
Noord-Holland
Country [49] 0 0
Netherlands
State/province [49] 0 0
North Holland
Country [50] 0 0
Netherlands
State/province [50] 0 0
South Holland
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
La Coruna
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Spain
State/province [54] 0 0
Sevilla
Country [55] 0 0
United Kingdom
State/province [55] 0 0
England
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Lancashire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03845166
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03845166