STELLAR-002: Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors
Study Details
Study Description
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 + bempegaldesleukin (triplet) in subjects with advanced solid tumors.
In the Expansion Stage, the safety and efficacy of XL092 as combination therapy will be further evaluated in tumor-specific Expansion Cohorts, which will enroll subjects with genitourinary cancers.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: XL092 + Nivolumab Dose-Escalation Cohorts Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Nivolumab
360 mg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 + Nivolumab + Ipilimumab Dose-Escalation Cohorts Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Ipilimumab
1 mg/kg IV infusion specified doses on specified days
Other Names:
Drug: Nivolumab
3 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 + Nivolumab + Bempegaldesleukin Dose-Escalation Cohorts Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Nivolumab
360 mg IV infusion specified doses on specified days
Other Names:
Drug: Bempegaldesleukin
0.006 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 + Nivolumab Expansion Cohorts The recommended dose from the dose-escalation stage may be further explored in genitourinary cancers. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Nivolumab
360 mg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 + Nivolumab + Ipilimumab Expansion Cohorts The recommended dose from the dose-escalation stage may be further explored in genitourinary cancers. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Ipilimumab
1 mg/kg IV infusion specified doses on specified days
Other Names:
Drug: Nivolumab
3 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 + Nivolumab + Bempegaldesleukin Expansion Cohorts The recommended dose from the dose-escalation stage may be further explored in genitourinary cancers. |
Drug: XL092
XL092 orally once daily (qd)
Drug: Nivolumab
360 mg IV infusion specified doses on specified days
Other Names:
Drug: Bempegaldesleukin
0.006 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: Nivolumab + Bempegaldesleukin Expansion Cohorts
|
Drug: Nivolumab
360 mg IV infusion specified doses on specified days
Other Names:
Drug: Bempegaldesleukin
0.006 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: Nivolumab + Ipilimumab Expansion Cohorts
|
Drug: Ipilimumab
1 mg/kg IV infusion specified doses on specified days
Other Names:
Drug: Nivolumab
3 mg/kg IV infusion specified doses on specified days
Other Names:
|
| Experimental: XL092 Single-Agent Expansion Cohorts
|
Drug: XL092
XL092 orally once daily (qd)
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including immune-mediated adverse events (imAEs) [up to 36 months]
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
- Expansion Stage: Objective Response Rate (ORR) [up to 24 months]
To evaluate ORR in subjects with measurable disease as assessed by the Investigator per RECIST 1.1
- Expansion Stage: Progression-Free Survival (PFS) [up to 24 months]
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)
Eligibility Criteria
Criteria
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.
-
Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
-
Must have progressed 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.
-
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, or maintenance therapy.
-
Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, sarcomatoid RCC (≥ 50% of the tumor has sarcomatoid features).
-
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 Cohorts 1, 2, 4, 5, 6: 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:
-
Prior treatment with XL092, nivolumab, ipilimumab, or agents targeting the IL-2 pathway such as bempegaldesleukin.
-
For Cohorts 2 (ccRCC), 3 (mCRPC), 4 and 5 (UC): 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 Cohorts 2 (ccRCC), 3 (mCRPC), 4 and 5 (UC): Receipt of any type of anticancer antibody or systemic chemotherapy within 3 weeks before first dose of study treatment.
-
Prior external radiation therapy within 2 weeks and prior radium-223 therapy within 6 weeks before first dose of study treatment.
-
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.
-
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.
-
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.
Note: Additional Inclusion and Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Exelixis Site #1 | Tucson | Arizona | United States | 85711 |
| 2 | Exelixis Clinical Site #4 | Indianapolis | Indiana | United States | 46250 |
| 3 | Exelixis Clinical Site #2 | Omaha | Nebraska | United States | 68130 |
| 4 | Exelixis Clinical Site #3 | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Exelixis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XL092-002