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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05176483




Registration number
NCT05176483
Ethics application status
Date submitted
15/12/2021
Date registered
4/01/2022
Date last updated
18/10/2024

Titles & IDs
Public title
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2023-510061-10-00
Secondary ID [2] 0 0
XL092-002
Universal Trial Number (UTN)
Trial acronym
STELLAR-002
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Metastatic Castration-resistant Prostate Cancer 0 0
Urothelial Carcinoma 0 0
Solid Tumor 0 0
Hepatocellular Carcinoma 0 0
Non-small Cell Lung Cancer 0 0
Colorectal Cancer 0 0
Head and Neck Squamous Cell Carcinoma 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
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zanzalintinib
Treatment: Drugs - Nivolumab
Treatment: Drugs - Ipilimumab
Treatment: Drugs - Nivolumab
Treatment: Drugs - Nivolumab
Treatment: Drugs - Nivolumab + Relatlimab

Experimental: Zanzalintinib + Nivolumab Dose-Escalation Cohorts - Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Experimental: Zanzalintinib + Nivolumab + Ipilimumab Dose-Escalation Cohorts - Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Experimental: Zanzalintinib + Nivolumab Expansion Cohorts - The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Experimental: Zanzalintinib + Nivolumab + Ipilimumab Expansion Cohorts - The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.

Experimental: Zanzalintinib Single-Agent Expansion Cohorts -

Experimental: Zanzalintinib + Nivolumab + Relatlimab Dose-Escalation Cohorts - Approximately 12 subjects will accrue across 1-2 dose levels of Zanzalintinib following the "rolling 6" design.

Experimental: Zanzalintinib + Nivolumab + Relatlimab Expansion Cohorts - The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.


Treatment: Drugs: Zanzalintinib
Zanzalintinib orally once daily (qd)

Treatment: Drugs: Nivolumab
360 mg IV infusion once every 3 weeks (q3w)

Treatment: Drugs: Ipilimumab
1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses

Treatment: Drugs: 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)

Treatment: Drugs: Nivolumab
480 mg IV infusion once every 4 weeks (q4w)

Treatment: Drugs: Nivolumab + Relatlimab
IV administration of nivolumab + relatlimab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including immune-mediated adverse events (imAEs)
Timepoint [1] 0 0
up to 36 months
Primary outcome [2] 0 0
Expansion Stage: Objective Response Rate (ORR)
Timepoint [2] 0 0
up to 24 months
Primary outcome [3] 0 0
Expansion Stage: Progression-Free Survival (PFS)
Timepoint [3] 0 0
up to 24 months
Primary outcome [4] 0 0
Expansion Stage: Overall Survival (OS)
Timepoint [4] 0 0
6 months

Eligibility
Key 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 novel hormone therapy (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, unclassified RCC, and translocation-associated, FH deficient and SDH deficient. 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 locally advanced, or metastatic and/or unresectable 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.
* Expansion Cohort 12 (ccRCC): Subjects with unresectable advance or metastatic RCC with a clear cell component, including subjects who also have a sacromatoid feature.

* Must have received no more than two prior lines of systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma
* Expansion Cohort 13 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear component, including subjects who also have a sacromatoid feature.
* For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
* For Expansion Cohorts 1 - 11 Only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
* Recovery to baseline or = Grade 1 common terminology criteria for adverse events (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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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), and Cohort 12 (ccRCC), and prior treatment in the neoadjuvant or adjuvant setting is allowed for Cohort 13 (ccRCC).
* For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC), Cohort 10 (CRC), and Cohort 12: 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), and Cohort 12: 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 and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
* Concomitant anticoagulation with oral anticoagulants, except for specified direct factor Xa inhibitors.
* Administration of a live, attenuated vaccine within 30 days prior to first dose.
* Uncontrolled, significant intercurrent or recent illness.
* Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms for females and > 450 ms for males 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 superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage = T2N0M0 and Gleason score = 6.
* 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 the first dose.
* 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 first dose.
* Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
* For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or trifluridine + tipiracil (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.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2026
Actual
Sample size
Target
1274
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Exelixis Clinical Site #116 - Albury
Recruitment hospital [2] 0 0
Exelixis Clinical Site #35 - Birtinya
Recruitment hospital [3] 0 0
Exelixis Clinical Site #16 - Brisbane
Recruitment hospital [4] 0 0
Exelixis Clinical Site #42 - Saint Leonards
Recruitment hospital [5] 0 0
Exelixis Clinical Site #36 - Sydney
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [5] 0 0
2109 - Sydney
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Connecticut
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Delaware
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Illinois
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Graz
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Wein
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Wien
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Kortrijk
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Paris
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Rennes
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Saint-Herblain
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Strasbourg
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Vandœuvre-lès-Nancy
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Villejuif
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Essen
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Hamburg
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Heidelberg
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Herne
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Jena
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Nürtingen
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Trier
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Tübingen
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Be'er Sheva
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Haifa
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Israel
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Zerifin
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Italy
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Ancona
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Italy
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Bologna
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Italy
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Firenze
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Italy
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Milano
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Italy
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Napoli
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Italy
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Ravenna
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New Zealand
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Grafton
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New Zealand
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Hamilton
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Poland
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Bydgoszcz
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Poland
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Gdansk
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Poland
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Otwock
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Poznan
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Wroclaw
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Badajoz
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Barcelona
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L'Hospitalet De Llobregat
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Madrid
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Pamplona
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Santander
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Seville
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Spain
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Valencia
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Switzerland
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Chur
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Switzerland
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St. Gallen
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Switzerland
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Winterthur
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United Kingdom
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Cambridge
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United Kingdom
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London
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United Kingdom
State/province [87] 0 0
Middlesex

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

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT05176483
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
Exelixis Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
1-888-EXELIXIS (888-393-5494)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05176483