STELLAR 002

Actively Recruiting

Phase 1b Dose-Escalation and Expansion Study of Zanzalintinib (XL092) in Combination With Immuno-oncology Agents in Advanced or Metastatic Solid Tumors

Uses and/or compounds described here are investigational. Safety and Efficacy have not been established.

Study Overview
Key Eligibility Criteria
Key Endpoints
Participating Sites

Study Overview

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

Identify RD of Zanzalintinib for Each Combination Therapy

Chart explaining dose-escalation stage of zanzalintinib with immuno-oncology agents nivolumab, nivolumab plus ipilimumab, and nivolumab plus relatlimab in unresectable advanced or metastatic solid tumors

Eligible patients will be treated with zanzalintinib in combination therapy using a “rolling 6” design to determine the recommended dose for each of the zanzalintinib combinations (doublet and triplets) for further investigation.

Key Eligibility Criteria

Unresectable or metastatic solid tumor for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective
No prior treatment with zanzalintinib

Following determination of the recommended dose, zanzalintinib alone and/or in combination therapy will be further evaluated in tumor-specific expansion cohorts. Patients in each cohort will be randomly assigned to treatment arms of single-agent zanzalintinib and/or zanzalintinib combination therapies.

Cohorts and Eligibility

Click “+” to expand and learn more

Actively recruiting

Not recruiting

Clear Cell Renal Cell Carcinoma, First-Line (ccRCC, 1L)

Unresectable advanced or metastatic RCC with clear cell component, including sarcomatoid features
No prior systemic therapy for RCC, with exception of 1 prior adjuvant or neoadjuvant therapy that did not include a VEGF or VEGFR-targeting agent, and if disease recurrence occurred ≥6 months after the last dose of therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agents nivolumab, nivolumab plus ipilimumab, and nivolumab plus relatlimab in clear cell renal cell carcinoma, first-line

Clear Cell Renal Cell Carcinoma, Second-Line (ccRCC, 2L)

Unresectable advanced or metastatic RCC with clear cell component, including sarcomatoid features
Progression during or after treatment with an ICI combination therapy (doublet) of a PD-1/PD-L1–targeting mAb + VEGFR-TKI or a PD-1–targeting mAb + anti–CTLA-4 mAb as preceding line of therapy; prior triplet combination therapy not allowed
Prior treatment with a LAG-3 inhibitor or triplet therapy allowed (including a VEGFR-TKI, PD-1/PD-L1–targeting mAb, and HIF-2 alpha inhibitors)
≤1 prior systemic anticancer therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib alone and with immuno-oncology agents nivolumab and nivolumab plus relatlimab in clear cell renal cell carcinoma, second-line

Metastatic Castration-Resistant Prostate Cancer, Second-Line Post–Novel Hormonal Therapy (mCRPC, 2L post-NHT)

Metastatic CRPC
Progression during or after one, and only one, NHT for locally advanced or mCSPC, M0 CRPC, or mCRPC
Progressive disease as defined by PSA or radiographic progression in soft tissue and/or bone
Prior taxane-based chemotherapy for mCRPC not allowed
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib alone and with immuno-oncology agents nivolumab and nivolumab plus ipilimumab in metastatic castration-resistant prostate cancer, second-line post-novel hormonal therapy

Urothelial Carcinoma, Immune Checkpoint Inhibitor–Naive (UC, ICI-naive)

Unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra)
Progression during or after prior first-line platinum-based combination therapy
≤1 prior line of systemic anticancer therapy
Recurrence ≤6 months following completion of adjuvant anti–PD-1/PD-L1 treatment not allowed
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agents nivolumab and nivolumab plus relatlimab in urothelial carcinoma, immune checkpoint inhibitor-naive

Urothelial Carcinoma, Immune Checkpoint Inhibitor–Experienced (UC, ICI-experienced)

Unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra)
Progression during or after prior PD-1/PD-L1–targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy, or adjuvant therapy (if <6 months from completion of therapy)
≤2 prior lines of systemic anticancer therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Non–Clear Cell Renal Cell Carcinoma, First-Line (nccRCC, 1L)

Unresectable advanced or metastatic nccRCC of the following subtypes: papillary, unclassified, and translocation-associated; sarcomatoid features allowed
No prior systemic anticancer therapy for nccRCC, with exception of 1 prior adjuvant therapy if it did not include an agent that targets VEGF or VEGFR, and if disease recurrence ≥6 months after the last dose of therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib alone and with immuno-oncology agent nivolumab in non–clear cell renal cell carcinoma, first-line

Hepatocellular Carcinoma, First-Line (HCC, 1L)

Inoperable, locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy
Child-Pugh score A
No prior systemic anticancer therapy for advanced disease
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agent nivolumab and nivolumab plus relatlimab in hepatocellular carcinoma, first-line

Non–Small Cell Lung Cancer, First-Line With Low PD-L1 Expression (NSCLC, 1L low PD-L1)

Stage IV nonsquamous NSCLC with positive PD-L1 expression (TPS 1-49%)
Diagnosis with an EGFR-sensitizing mutation, ALK rearrangement, ROS1 rearrangement, or BRAF V600E mutation not allowed
No prior systemic anticancer therapy for metastatic disease
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agent nivolumab and nivolumab plus relatlimab in non–small cell lung cancer, first-line

Non–Small Cell Lung Cancer, Second- and Later-Line (NSCLC, 2L+)

Stage IV nonsquamous NSCLC that has radiologically progressed following treatment with 1 prior ICI for metastatic disease
Diagnosis with an EGFR-sensitizing mutation, ALK rearrangement, ROS1 rearrangement, or BRAF V600E mutation not allowed
≤2 lines of prior systemic anticancer therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Microsatellite Stable Metastatic Colorectal Cancer, Second- and Later-Line (MSS mCRC, 2L+)

Unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum
Known RAS status
MSI-high or dMMR CRC not allowed
Progressed, refractory, or intolerant to all the following SOC regimens for mCRC
- Fluoropyrimidine, irinotecan, and oxaliplatin, +/- anti-VEGF mAb
- Anti-EGFR mAb
- BRAF inhibitor for known BRAF V600E mutations
Progression ≤4 months following last dose of SOC regimen
No prior therapy with regorafenib and/or TAS-102 allowed
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agent nivolumab and nivolumab plus relatlimab in microsatellite stable metastatic colorectal cancer, second- and later-line

Head and Neck Squamous Cell Carcinoma, Immune Checkpoint Inhibitor–Naive (HNSCC, ICI-naive)

Inoperable, refractory, recurrent, or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx; nasopharynx not allowed
PD-L1 CPS ≥1
≤1 prior radiotherapy regimen
No prior systemic anticancer therapy
No prior treatment with zanzalintinib, nivolumab, ipilimumab, or relatlimab, except as indicated in specific cohorts

Chart explaining cohort expansion stage of zanzalintinib with immuno-oncology agent nivolumab and nivolumab plus relatlimab in head and neck squamous cell carcinoma, immune checkpoint inhibitor-naive

Key Endpoints

Dose-Escalation Stage

Primary Endpoint

Determine the safety and RD of the
combination therapies

Exploratory Endpoints

ORR and DOR by investigator
PFS by investigator
PK

Cohort Expansion Stage

Primary Endpoints

ORR by investigator
Safety
mCRPC cohort: duration of
radiographic PFS by BIRC
CRC cohort: OS at 6 months

Secondary Endpoints

DOR by investigator
PFS by investigator

Additional Endpoints

ORR, DOR, and PFS by BIRC
OS
mCRPC cohort:

Response based on >50% decrease in PSA from baseline
Change in bone biomarkers

1L, first-line; 2L, second-line; 2L+, second- and later-line; ALK, anaplastic lymphoma kinase; BIRC, blinded independent radiology committee; ccRCC, clear cell renal cell carcinoma; CPS, combined positive score; CRC, colorectal cancer; CRPC, castration-resistant prostate cancer; CTLA-4, cytotoxic T-lymphocyte–associated protein 4; dMMR, deficient mismatch repair; DOR, duration of response; EGFR, epidermal growth factor receptor; FDC, fixed-dose combination; HCC, hepatocellular carcinoma; HIF-2, hypoxia-inducible factor-2; HNSCC, head and neck squamous cell carcinoma; ICI, immune checkpoint inhibitor; IV, intravenous; LAG-3, lymphocyte activation gene-3; M0 CRPC, non-metastatic castration-resistant prostate cancer; mAb, monoclonal antibody; mCRC, metastatic colorectal cancer; mCRPC, metastatic castration-resistant prostate cancer; mCSPC, metastatic castration-sensitive prostate cancer; MSI-high, microsatellite instability–high; MSS, microsatellite stable; MTD, maximum tolerated dose; nccRCC, non–clear cell renal cell carcinoma; NHT, novel hormonal therapy; NSCLC, non–small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-1, programmed death receptor-1; PD-L1, programmed death receptor-1 ligand; PFS, progression-free survival; PK, pharmacokinetics; PSA, prostate-specific antigen; q3w, once every 3 weeks; q4w, once every 4 weeks; qd, once daily; RCC, renal cell carcinoma; RD, recommended dose; SOC, standard of care; TKI, tyrosine kinase inhibitor; TPS, tumor proportion score; UC, urothelial carcinoma; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

Participating Sites

STELLAR-002 will be conducted in North America, Europe, Middle East, and Asia Pacific. Call 1-888-393-5494 (toll-free) or 1-303-389-1847 for specific location and site information and to confirm whether sites near you are still enrolling new patients.

Currently open or planned clinical site cities:

Trial sites may stop enrolling patients at any time. Please check back if you do not see a trial site located near you.

To learn more about this trial, go to clinicaltrials.gov and search for NCT05176483, or contact Exelixis Medical Information at 1-888-393-5494 (toll-free),
1-303-389-1847, or medinfo@exelixis.com.