Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors

Colorectal Cancer Clinical Trial

— STELLAR-002  

Official title:

A Dose-Escalation and Expansion Study of the Safety and Efficacy of XL092 in Combination With Immuno-Oncology Agents in Subjects With Unresectable Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05176483
• Other study ID #: XL092-002
• Status: Recruiting
• Phase: Phase 1
• Start date: December 14, 2021
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: Exelixis
• Contact: Exelixis Clinical Trials
• Phone: 1-888-EXELIXIS (888-393-5494)
• Email: druginfo[@]exelixis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors.

In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1078
• Est. completion date: May 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.

• Dose-Escalation Cohorts: 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 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.

• Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.

• Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component.

• Must have radiographically progressed after a combination therapy consisting of a PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.

• Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.

• Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.

• Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.

• Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).

• Must have progressed during or after prior first-line platinum-based combination therapy, including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.

• Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.

• Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).

• Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.

• Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.

• Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.

• No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.

• Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.

• Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.

• Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.

• Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.

• Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) =1.

• For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.

• For expansion cohorts only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.

• Recovery to baseline or = Grade 1 CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.

• Karnofsky Performance Status (KPS) = 70%.

• 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:

• For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).

• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.

• For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.

• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.

• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.

• Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.

• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before first dose of study treatment.

• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.

• Administration of a live, attenuated vaccine within 30 days prior to enrollment.

• Uncontrolled, significant intercurrent or recent illness.

• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.

• Subjects with inadequately treated adrenal insufficiency.

• Pregnant or lactating females.

• Any other active malignancy within two years before first dose of study treatment, except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

• For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.

• For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.

• For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.

• For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.

• For Cohort 7 (HCC):

• Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).

• Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.

• Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.

• Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma

• For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.

• For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.

• For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):

• Troponin T (TnT) or I (TnI) > 2 × institutional ULN.

Note: Additional Inclusion and Exclusion criteria may apply.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Colorectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Hepatocellular Carcinoma
• Metastatic Castration-resistant Prostate Cancer
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Solid Tumor
• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma

Intervention

Drug:
• XL092
XL092 orally once daily (qd)
• Nivolumab
360 mg IV infusion once every 3 weeks (q3w)
• Ipilimumab
1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
• Nivolumab
3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
• Nivolumab
480 mg IV infusion once every 4 weeks (q4w)
• Nivolumab + Relatlimab
IV administration of nivolumab + relatlimab

Locations

Country	Name	City	State
Australia	Exelixis Clinical Site #116	Albury
Australia	Exelixis Clinical Site #35	Birtinya
Australia	Exelixis Clinical Site #16	Brisbane
Australia	Exelixis Clinical Site #42	Saint Leonards
Australia	Exelixis Clinical Site #36	Sydney
Austria	Exelixis Clinical Site #94	Graz
Austria	Exelixis Clinical Site #31	Salzburg
Austria	Exelixis Clinical Site #106	Wein
Austria	Exelixis Clinical Site #29	Wien
Belgium	Exelixis Clinical Site #39	Anderlecht
Belgium	Exelixis Clinical Site #37	Kortrijk
France	Exelixis Clinical Site #85	Besançon
France	Exelixis Clinical Site #96	Bordeaux
France	Exelixis Clinical Site #79	Caen
France	Exelixis Clinical Site #118	Clermont-Ferrand
France	Exelixis Clinical Site #109	Lyon
France	Exelixis Clinical Site #92	Marseille
France	Exelixis Clinical Site #64	Nice
France	Exelixis Clinical Site #83	Paris
France	Exelixis Clinical Site #91	Paris
France	Exelixis Clinical Site #80	Rennes
France	Exelixis Clinical Site #63	Saint-Herblain
France	Exelixis Clinical Site #75	Strasbourg
France	Exelixis Clinical Site #84	Vandœuvre-lès-Nancy
France	Exelixis Clinical Site #115	Villejuif
Germany	Exelixis Clinical Site #103	Essen
Germany	Exelixis Clinical Site #113	Hamburg
Germany	Exelixis Clinical Site #108	Heidelberg
Germany	Exelixis Clinical Site #82	Herne
Germany	Exelixis Clinical Site #93	Jena
Germany	Exelixis Clinical Site #112	München
Germany	Exelixis Clinical Site #102	Nürtingen
Germany	Exelixis Clinical Site #107	Trier
Germany	Exelixis Clinical Site #95	Tübingen
Israel	Exelixis Clinical Site #86	Be'er Sheva
Israel	Exelixis Clinical Site #72	Haifa
Israel	Exelixis Clinical Site #52	Jerusalem
Israel	Exelixis Clinical Site #71	Petah Tikva
Israel	Exelixis Clinical Site #69	Tel Aviv
Israel	Exelixis Clinical Site #38	Zerifin
Italy	Exelixis Clinical Site #121	Ancona
Italy	Exelixis Clinical Site #117	Bologna
Italy	Exelixis Clinical Site #90	Firenze
Italy	Exelixis Clinical Site #101	Milano
Italy	Exelixis Clinical Site #81	Milano
Italy	Exelixis Clinical Site #40	Napoli
Italy	Exelixis Clinical Site #74	Ravenna
New Zealand	Exelixis Clinical Site #30	Grafton
New Zealand	Exelixis Clinical Site #45	Hamilton
Poland	Exelixis Clinical Site #20	Bydgoszcz
Poland	Exelixis Clinical Site #28	Gdansk
Poland	Exelixis Clinical Site #34	Otwock
Poland	Exelixis Clinical Site #54	Poznan
Poland	Exelixis Clinical Site #114	Wroclaw
Spain	Exelixis Clinical Site #41	Badajoz
Spain	Exelixis Clinical Site #15	Barcelona
Spain	Exelixis Clinical Site #27	Barcelona
Spain	Exelixis Clinical Site #53	Barcelona
Spain	Exelixis Clinical Site #120	L'Hospitalet De Llobregat
Spain	Exelixis Clinical Site #100	Madrid
Spain	Exelixis Clinical Site #19	Madrid
Spain	Exelixis Clinical Site #43	Madrid
Spain	Exelixis Clinical Site #57	Madrid
Spain	Exelixis Clinical Site #58	Madrid
Spain	Exelixis Clinical Site #77	Madrid
Spain	Exelixis Clinical Site #18	Pamplona
Spain	Exelixis Clinical Site #119	Santander
Spain	Exelixis Clinical Site #23	Seville
Spain	Exelixis Clinical Site #25	Valencia
Spain	Exelixis Clinical Site #56	Valencia
Switzerland	Exelixis Clinical Site #21	Chur
Switzerland	Exelixis Clinical Site #22	St. Gallen
Switzerland	Exelixis Clinical Site #44	Winterthur
United Kingdom	Exelixis Clinical Site #110	Cambridge
United Kingdom	Exelixis Clinical Site #99	London
United Kingdom	Exelixis Clinical Site #97	Middlesex
United States	Exelixis Clinical Site #46	Austin	Texas
United States	Exelixis Clinical Site #14	Baltimore	Maryland
United States	Exelixis Clinical Site #7	Boston	Massachusetts
United States	Exelixis Clinical Site #48	Celebration	Florida
United States	Exelixis Clinical Site #66	Charlottesville	Virginia
United States	Exelixis Clinical Site #26	Chicago	Illinois
United States	Exelixis Clinical Site #10	Cleveland	Ohio
United States	Exelixis Clinical Site #111	Dallas	Texas
United States	Exelixis Clinical Site #89	Dallas	Texas
United States	Exelixis Clinical Site #13	Detroit	Michigan
United States	Exelixis Clinical Site #65	Detroit	Michigan
United States	Exelixis Clinical Site #12	Durham	North Carolina
United States	Exelixis Clinical Site #88	East Brunswick	New Jersey
United States	Exelixis Clinical Site #11	Gainesville	Florida
United States	Exelixis Clinical Site #105	Hackensack	New Jersey
United States	Exelixis Clinical Site #104	Hershey	Pennsylvania
United States	Exelixis Clinical Site #4	Indianapolis	Indiana
United States	Exelixis Clinical Site #73	Irving	Texas
United States	Exelixis Clinical Site #78	Jacksonville	Florida
United States	Exelixis Clinical Site #55	Las Vegas	Nevada
United States	Exelixis Clinical Site #87	Littleton	Colorado
United States	Exelixis Clinical Site #122	Louisville	Kentucky
United States	Exelixis Clinical Site #47	Miami	Florida
United States	Exelixis Clinical Site #33	Milwaukee	Wisconsin
United States	Exelixis Clinical Site #9	Myrtle Beach	South Carolina
United States	Exelixis Clinical Site #3	Nashville	Tennessee
United States	Exelixis Clinical Site #62	New Haven	Connecticut
United States	Exelixis Clinical Site #6	New York	New York
United States	Exelixis Clinical Site #60	New York	New York
United States	Exelixis Clinical Site #49	Newark	Delaware
United States	Exelixis Clinical Site #2	Omaha	Nebraska
United States	Exelixis Clinical Site #5	Omaha	Nebraska
United States	Exelixis Clinical Site #123	Palo Alto	California
United States	Exelixis Clinical Site #98	Philadelphia	Pennsylvania
United States	Exelixis Clinical Site #67	Phoenix	Arizona
United States	Exelixis Clinical Site #24	Pittsburgh	Pennsylvania
United States	Exelixis Clinical Site #32	Pittsburgh	Pennsylvania
United States	Exelixis Clinical Site #50	Plano	Texas
United States	Exelixis Clinical Site #61	Plantation	Florida
United States	Exelixis Clinical Site #51	Portland	Oregon
United States	Exelixis Clinical Site #68	Rochester	Minnesota
United States	Exelixis Clinical Site #59	Santa Barbara	California
United States	Exelixis Clinical Site #76	Syracuse	New York
United States	Exelixis Clinical Site #8	Tampa	Florida
United States	Exelixis Clinical Site #1	Tucson	Arizona
United States	Exelixis Clinical Site #70	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Germany,  Israel,  Italy,  New Zealand,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including immune-mediated adverse events (imAEs)	To evaluate the safety of XL092 when administered alone or in combination therapy regimens through the evaluation of incidence and severity of AEs and SAEs, including imAEs	up to 36 months
Primary	Expansion Stage: Objective Response Rate (ORR)	To evaluate ORR in subjects with measurable disease as assessed by the Investigator per RECIST 1.1	up to 24 months
Primary	Expansion Stage: Progression-Free Survival (PFS)	For Cohort 3 (mCRPC): To evaluate duration of radiographic PFS as determined per Prostate Working Group 3 (PCWG3) criteria (Scher et al 2016) by Blinded Independent Radiology Committee (BIRC)	up to 24 months
Primary	Expansion Stage: Overall Survival (OS)	For Cohort 10 (CRC): Overall Survival (OS) rate	6 months