Brief Title
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including immune-mediated adverse events (imAEs)
Condition
Renal Cell Carcinoma
Intervention
XL092
Study Arms / Comparison Groups
XL092 + Nivolumab Dose-Escalation Cohorts
Description: Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
826
Start Date
December 14, 2021
Completion Date
May 2026
Primary Completion Date
February 2026
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 1-888-EXELIXIS (888-393-5494), [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05176483
Organization ID
XL092-002
Responsible Party
Sponsor
Study Sponsor
Exelixis
Study Sponsor
, ,
Verification Date
December 2021