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

Colorectal Cancer Clinical Trial

— STELLAR-001  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03845166
• Other study ID #: XL092-001
• Secondary ID: 2020-003569-21
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 20, 2019
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 325
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• XL092
oral doses of XL092
• 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)

Locations

Country	Name	City	State
Australia	Exelixis Clinical Site #52	Darlinghurst	New South Wales
Australia	Exelixis Clinical Site #63	Heidelberg	Victoria
Australia	Exelixis Clinical Site #56	Kurralta Park	South Australia
Australia	Exelixis Clinical Site #53	Liverpool	New South Wales
Australia	Exelixis Clinical #75	South Brisbane	Queensland
Belgium	Exelixis Clinical Site #51	Bruxelles	Brussels
Belgium	Exelixis Clinical Site #44	Edegem	Antwerpen
Belgium	Exelixis Clinical Site #65	Gent	Oost-Vlaanderen
Czechia	Exelixis Clinical Site #21	Brno
Czechia	Exelixis Clinical Site #42	Hradec Králové
Czechia	Exelixis Clinical Site #10	Olomouc
Czechia	Exelixis Clinical Site #27	Praha
France	Exelixis Clinical #72	Bordeaux
France	Exelixis Clinical Site #32	Caen Cedex 5
France	Exelixis Clinical Site #46	Clermont	Ferrand
France	Exelixis Clinical Site #48	Marseille
France	Exelixis Clinical Site #14	Paris
France	Exelixis Clinical Site #39	Pierre-Bénite
France	Exelixis Clinical Site #47	Poitiers
France	Exelixis Clinical Site #37	Saint-Herblain Cedex	Loire Atlantique
France	Exelixis Clinical Site #22	Suresnes
France	Exelixis Clinical Site #57	Toulouse Cedex 9
France	Exelixis Clinical #77	Villejuif
Germany	Exelixis Clinical Site #64	Hamburg
Germany	Exelixis Clinical Site #28	München	Bavaria
Germany	Exelixis Clinical Site #31	Münster	North Rhine-Westphalia
Germany	Exelixis Clinical Site #38	Nürtingen	Baden-Wuerttemberg
Italy	Exelixis Clinical Site #54	Milan
Italy	Exelixis Clinical Site #67	Milano	MI
Italy	Exelixis Clinical #73	Napoli
Italy	Exelixis Clinical Site #69	Pavia	PV
Netherlands	Exelixis Clinical Site #79	Amsterdam	Noord-Holland
Netherlands	Exelixis Clinical Site #82	Amsterdam	North Holland
Netherlands	Exelixis Clinical #76	Rotterdam	South Holland
Spain	Exelixis Clinical Site #18	Barcelona
Spain	Exelixis Clinical Site #19	Barcelona
Spain	Exelixis Clinical Site #29	Barcelona
Spain	Exelixis Clinical Site #30	Barcelona
Spain	Exelixis Clinical Site #17	Madrid
Spain	Exelixis Clinical Site #34	Madrid
Spain	Exelixis Clinical Site #55	Madrid
Spain	Exelixis Clinical Site #81	Madrid
Spain	Exelixis Clinical Site #23	Sabadell	Barcelona
Spain	Exelixis Clinical Site #20	Santiago De Compostela	La Coruna
Spain	Exelixis Clinical Site #16	Sevilla
United Kingdom	Exelixis Clinical #70	London	England
United Kingdom	Exelixis Clinical Site #68	Preston	Lancashire
United Kingdom	Exelixis Clinical Site #40	Sutton	England
United States	Exelixis Clinical Site #45	Ann Arbor	Michigan
United States	Exelixis Clinical Site #11	Atlanta	Georgia
United States	Exelixis Clinical Site #80	Atlanta	Georgia
United States	Exelixis Clinical Site #44	Baltimore	Maryland
United States	Exelixis Clinical Site #4	Boston	Massachusetts
United States	Exelixis Clinical Site #61	Charleston	South Carolina
United States	Exelixis Clinical Site #8	Charlottesville	Virginia
United States	Exelixis Clinical #74	Cincinnati	Ohio
United States	Exelixis Clinical Site #60	Cleveland	Ohio
United States	Exelixis Clinical Site #6	Duarte	California
United States	Exelixis Clinical Site #9	East Brunswick	New Jersey
United States	Exelixis Clinical Site #33	Germantown	Tennessee
United States	Exelixis Clinical Site #2	Grand Rapids	Michigan
United States	Exelixis Clinical Site #59	Hershey	Pennsylvania
United States	Exelixis Clinical Site #3	Houston	Texas
United States	Exelixis Clinical Site #41	Iowa City	Iowa
United States	Exelixis Clinical Site #49	La Jolla	California
United States	Exelixis Clinical Site #15	Lake Mary	Florida
United States	Exelixis Clinical Site #7	Los Angeles	California
United States	Exelixis Clinical Site #24	Miami	Florida
United States	Exelixis Clinical Site #50	Myrtle Beach	South Carolina
United States	Exelixis Clinical Site #83	New Brunswick	New Jersey
United States	Exelixis Clinical #78	New York	New York
United States	Exelixis Clinical Site #35	New York	New York
United States	Exelixis Clinical Site #13	Omaha	Nebraska
United States	Exelixis Clinical #71	Palo Alto	California
United States	Exelixis Clinical Site #58	Philadelphia	Pennsylvania
United States	Exelixis Clinical Site #12	Pittsburgh	Pennsylvania
United States	Exelixis Clinical Site #43	Richmond	Virginia
United States	Exelixis Clinical Site #25	Saint Paul	Minnesota
United States	Exelixis Clinical Site #5	Salt Lake City	Utah
United States	Exelixis Clinical Site #1	San Antonio	Texas
United States	Exelixis Clinical Site #66	San Francisco	California
United States	Exelixis Clinical Site #62	Scarborough	Maine
United States	Exelixis Clinical Site #26	Spokane	Washington
United States	Exelixis Clinical Site #36	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Up to 24 months
Primary	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	Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs)	To evaluate the safety of XL092 when administered alone and in combination with ICIs through the evaluation of incidence and severity of nonserious AEs and SAEs, including immune-related adverse events (irAEs), and adverse events of special interest (AESIs)	Up to 36 months
Secondary	Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)	To evaluate the Tmax of XL092 alone and in combination with ICI	Up to 24 months
Secondary	Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)	To evaluate the Cmax of XL092 alone and in combination with ICI	Up to 24 months
Secondary	Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)	To evaluate the AUC 0-24 of XL092 alone and in combination with ICI	Up to 24 months
Secondary	Dose-Escalation Stage: Terminal Half-Life	To evaluate the terminal half-life of XL092 alone and in combination with ICI	Up to 24 months
Secondary	Dose-Escalation Stage: Apparent Clearance (CL/F)	To evaluate the CL/F of XL092 alone and in combination with ICI	Up to 24 months