Status:
ACTIVE_NOT_RECRUITING
A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors
Lead Sponsor:
Exelixis
Conditions:
Neoplasm Malignant
Renal Cell Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers of XL092 admini...
Eligibility Criteria
Inclusion
- Cytologically or histologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent.
- Dose-escalation (single-agent and combination therapy): 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 A (ccRCC): Subjects with previously treated advanced RCC with clear cell histology (including those with a sarcomatoid component) who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
- Expansion Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with non-clear cell histology who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
- Expansion Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor receptor 2 (HER-2) and who have radiographically progressed during or following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.
- Expansion Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of the prostate). Neuroendocrine differentiation and other features permitted if adenocarcinoma is the primary histology.
- Expansion Cohort H (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum, KRAS/NRAS wild-type (confirmed via local testing report) and determined NOT to have microsatellite instability high (MSI-high) or mismatch repair deficient (dMMR) by local testing, who received the following standard of care chemotherapy regimens as prior therapy for metastatic CRC:
- Fluoropyrimidine, irinotecan and oxaliplatin, with or without an anti-VEGF monoclonal antibody (bevacizumab)
- Anti-EGFR monoclonal antibody (cetuximab or panitumumab)
- BRAF inhibitor (in combination with cetuximab +/- binimetinib) for subjects with BRAF V600E mutations
- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1.
- Tumor tissue material:
- Subjects in the non-biomarker cohort provide archival, if available, or fresh tumor tissue if it can be safely obtained.
- Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- 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
- Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, and H only), or prior treatment with regorafenib and/or TAS-102 (Cohort H only).
- Receipt of any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.
- Receipt of any type of anticancer antibody, systemic chemotherapy, or hormonal anticancer therapy within 4 weeks before first dose of study treatment.
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- 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.
- Uncontrolled, significant intercurrent or recent illness.
- Concomitant use of certain medications.
- Corrected QT interval calculated by the Fridericia formula (QTcF) \> 450 ms for males and \> 470 ms for females. Single ECGs are no longer permitted.
- Pregnant or lactating females.
- Diagnosis of another malignancy within 2 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.
- Additional Exclusion Criteria for XL092 + Atezolizumab Combination Therapy Cohorts ONLY:
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
- Additional Exclusion Criteria for XL092 + Avelumab Combination Therapy Cohorts ONLY:
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
Key Trial Info
Start Date :
March 20 2019
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 31 2027
Estimated Enrollment :
325 Patients enrolled
Trial Details
Trial ID
NCT03845166
Start Date
March 20 2019
End Date
May 31 2027
Last Update
November 19 2024
Active Locations (86)
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1
Exelixis Clinical Site #6
Duarte, California, United States, 91010
2
Exelixis Clinical Site #49
La Jolla, California, United States, 92093
3
Exelixis Clinical Site #7
Los Angeles, California, United States, 90025
4
Exelixis Clinical Site #84
Los Angeles, California, United States, 90095