STELLAR-001: A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

Sponsor

Exelixis (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03845166

Collaborator

(none)

800

Enrollment

Locations

Arms

67.4

Anticipated Duration (Months)

14.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Malignant Renal Cell Carcinoma Hormone Receptor Positive Breast Carcinoma Metastatic Castration-resistant Prostate Cancer Urothelial Carcinoma Colorectal Cancer	Drug: XL092 Drug: Atezolizumab Drug: Avelumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

single-agent and combination therapy dose-escalation followed by cohort-expansionsingle-agent and combination therapy dose-escalation followed by cohort-expansion

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 20, 2019

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XL092 Single-Agent Dose-Escalation Cohorts Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.	Drug: XL092 oral doses of XL092
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).	Drug: XL092 oral doses of XL092
Experimental: XL092 + Atezolizumab Dose-Escalation Cohorts Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.	Drug: XL092 oral doses of XL092 Drug: Atezolizumab Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w) Other Names: Tecentriq®
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).	Drug: XL092 oral doses of XL092 Drug: Atezolizumab Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w) Other Names: Tecentriq®
Experimental: XL092 + Avelumab Dose-Escalation Cohorts Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.	Drug: XL092 oral doses of XL092 Drug: Avelumab Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w) Other Names: Bavencio®
Experimental: XL092 + Avelumab Expansion Cohorts The MTD or recommended dose from the dose-escalation stage may be further explored in advanced urothelial carcinoma (UC).	Drug: XL092 oral doses of XL092 Drug: Avelumab Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w) Other Names: Bavencio®

Outcome Measures

Primary Outcome Measures

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: 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

Secondary Outcome Measures

Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 36 months]
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)
Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) [Up to 24 months]
To evaluate the Tmax of XL092 alone and in combination with ICI
Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) [Up to 24 months]
To evaluate the Cmax of XL092 alone and in combination with ICI
Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) [Up to 24 months]
To evaluate the AUC 0-24 of XL092 alone and in combination with ICI
Dose-Escalation Stage: Terminal Half-Life [Up to 24 months]
To evaluate the terminal half-life of XL092 alone and in combination with ICI
Dose-Escalation Stage: Apparent Clearance (CL/F) [Up to 24 months]
To evaluate the CL/F of XL092 alone and in combination with ICI

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 who received prior fluoropyrimidine-containing chemotherapy with oxaliplatin or irinotecan.
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.
Subjects in the Biomarker Cohorts provide fresh tumor and skin biopsies.
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 medically accepted 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) or prior avelumab (Cohort J 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) > 460 ms within 10 days per electrocardiogram (ECG) before first dose of study treatment.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Exelixis Clinical Site #6	Duarte	California	United States	91010
2	Exelixis Clinical Site #49	La Jolla	California	United States	92093
3	Exelixis Clinical Site #7	Los Angeles	California	United States	90025
4	Exelixis Clinical Site #15	Lake Mary	Florida	United States	32746
5	Exelixis Clinical Site #24	Miami	Florida	United States	33136
6	Exelixis Clinical Site #11	Atlanta	Georgia	United States	30341
7	Exelixis Clinical Site #41	Iowa City	Iowa	United States	52242
8	Exelixis Clinical Site #36	Westwood	Kansas	United States	66205
9	Exelixis Clinical Site #44	Baltimore	Maryland	United States	21201
10	Exelixis Clinical Site #4	Boston	Massachusetts	United States	02215
11	Exelixis Clinical Site #45	Ann Arbor	Michigan	United States	48109
12	Exelixis Clinical Site #2	Grand Rapids	Michigan	United States	49546
13	Exelixis Clinical Site #25	Saint Paul	Minnesota	United States	55101
14	Exelixis Clinical Site #13	Omaha	Nebraska	United States	68130
15	Exelixis Clinical Site #9	East Brunswick	New Jersey	United States	08816
16	Exelixis Clinical Site #35	New York	New York	United States	10029
17	Exelixis Clinical Site #12	Pittsburgh	Pennsylvania	United States	15232
18	Exelixis Clinical Site #50	Myrtle Beach	South Carolina	United States	29572
19	Exelixis Clinical Site #33	Germantown	Tennessee	United States	38138
20	Exelixis Clinical Site #3	Houston	Texas	United States	77030
21	Exelixis Clinical Site #1	San Antonio	Texas	United States	78229
22	Exelixis Clinical Site #5	Salt Lake City	Utah	United States	84112
23	Exelixis Clinical Site #8	Charlottesville	Virginia	United States	22903
24	Exelixis Clinical Site #43	Richmond	Virginia	United States	23219
25	Exelixis Clinical Site #26	Spokane	Washington	United States	99208
26	Exelixis Clinical Site #52	Darlinghurst	New South Wales	Australia	2010
27	Exelixis Clinical Site #53	Liverpool	New South Wales	Australia	2170
28	Exelixis Clinical Site #44	Edegem	Antwerpen	Belgium	2650
29	Exelixis Clinical Site #51	Bruxelles	Brussels	Belgium	1200
30	Exelixis Clinical Site #21	Brno		Czechia	656 91
31	Exelixis Clinical Site #42	Hradec Králové		Czechia	500 05
32	Exelixis Clinical Site #10	Olomouc		Czechia	779 00
33	Exelixis Clinical Site #27	Praha		Czechia	140 59
34	Exelixis Clinical Site #46	Clermont	Ferrand	France	63011
35	Exelixis Clinical Site #37	Saint-Herblain Cedex	Loire Atlantique	France	44805
36	Exelixis Clinical Site #32	Caen Cedex 5		France	14076
37	Exelixis Clinical Site #48	Marseille		France	13009
38	Exelixis Clinical Site #14	Paris		France	75015
39	Exelixis Clinical Site #39	Pierre-Bénite		France	69310
40	Exelixis Clinical Site #47	Poitiers		France	86000
41	Exelixis Clinical Site #22	Suresnes		France	92150
42	Exelixis Clinical Site #38	Nürtingen	Baden-Wuerttemberg	Germany	72622
43	Exelixis Clinical Site #28	München	Bavaria	Germany	81675
44	Exelixis Clinical Site #31	Münster	North Rhine-Westphalia	Germany	48149
45	Exelixis Clinical Site #54	Milan		Italy	20141
46	Exelixis Clinical Site #23	Sabadell	Barcelona	Spain	08208
47	Exelixis Clinical Site #20	Santiago De Compostela	La Coruna	Spain	15706
48	Exelixis Clinical Site #18	Barcelona		Spain	08003
49	Exelixis Clinical Site #19	Barcelona		Spain	08023
50	Exelixis Clinical Site #29	Barcelona		Spain	08035
51	Exelixis Clinical Site #30	Barcelona		Spain	08036
52	Exelixis Clinical Site #34	Madrid		Spain	28040
53	Exelixis Clinical Site #55	Madrid		Spain	28041
54	Exelixis Clinical Site #17	Madrid		Spain	28046
55	Exelixis Clinical Site #16	Sevilla		Spain	41013
56	Exelixis Clinical Site #40	Sutton	England	United Kingdom	SM2 5PT