A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (STELLAR-001)
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| ClinicalTrials.gov Identifier: NCT03845166 |
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Recruitment Status :
Recruiting
First Posted : February 19, 2019
Last Update Posted : December 23, 2022
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Sponsor:
Exelixis
Information provided by (Responsible Party):
Exelixis
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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 administered alone, in combination with atezolizumab, and in combination with avelumab to subjects with advanced solid tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasm Malignant Renal Cell Carcinoma Hormone Receptor Positive Breast Carcinoma Metastatic Castration-resistant Prostate Cancer Urothelial Carcinoma Colorectal Cancer | Drug: XL092 Drug: Atezolizumab Drug: Avelumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1195 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | single-agent and combination therapy dose-escalation followed by cohort-expansion |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors |
| Actual Study Start Date : | March 20, 2019 |
| Estimated Primary Completion Date : | November 2023 |
| Estimated Study Completion Date : | November 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: XL092 Single-Agent Dose-Escalation Cohorts
Subjects will accrue in cohorts of 3-6 subjects in a standard "3 plus 3" design.
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Drug: XL092
oral doses of XL092 |
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Experimental: XL092 Single-Agent Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in clear cell renal cell carcinoma (ccRCC), non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), and metastatic castration-resistant prostate cancer (mCRPC).
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Drug: XL092
oral doses of XL092 |
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Experimental: XL092 + Atezolizumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
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Drug: XL092
oral doses of XL092 Drug: Atezolizumab Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)
Other Name: Tecentriq® |
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Experimental: XL092 + Atezolizumab Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in non-clear cell renal cell carcinoma (nccRCC), hormone receptor-positive breast cancer (HR+ BC), metastatic castration-resistant prostate cancer (mCRPC), and colorectal cancer (CRC).
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Drug: XL092
oral doses of XL092 Drug: Atezolizumab Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once every 3 weeks (q3w)
Other Name: Tecentriq® |
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Experimental: XL092 + Avelumab Dose-Escalation Cohorts
Subjects will accrue in cohorts of 2-6 subjects in a "rolling 6" design.
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Drug: XL092
oral doses of XL092 Drug: Avelumab Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)
Other Name: Bavencio® |
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Experimental: XL092 + Avelumab Expansion Cohorts
The MTD or recommended dose from the dose-escalation stage may be further explored in advanced urothelial carcinoma (UC).
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Drug: XL092
oral doses of XL092 Drug: Avelumab Supplied as 200 mg/10 mL vials; administered as an 800 mg IV infusion once every 2 weeks (q2w)
Other Name: Bavencio® |
Primary Outcome Measures :
- Dose-Escalation Stage: MTD/recommended dose for XL092 [ Time Frame: Up to 24 months ]To determine the maximum tolerated dose (MTD) and/or recommended dose (RD) for further evaluation of XL092 when administered alone and in combination with immune checkpoint inhibitors (ICIs) to subjects with advanced solid tumors
- Cohort-Expansion Stage: Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]To evaluate preliminary efficacy of XL092 when administered alone and in combination with ICIs by estimating ORR as assessed by the Investigator per RECIST 1.1
- Cohort-Expansion Stage (except Cohort H): Progression-Free Survival (PFS) [ Time Frame: Up to 24 months ]To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with ICIs for specific cohorts by estimating the percentage of subjects with PFS at 6 months (PFS rate) per RECIST 1.1 as assessed by the Investigator
- Cohort-Expansion Stage (Cohort H only): Overall Survival (OS) [ Time Frame: Up to 24 months ]To evaluate preliminary efficacy of single-agent XL092 and XL092 in combination with atezolizumab for subjects with RAS wild-type CRC (Cohort H Treatment Arms H-A and H-B) by estimating overall survival (OS)
Secondary Outcome Measures :
- Incidence and Severity of Nonserious Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months ]To evaluate the safety of XL092 when administered alone and in combination with ICIs through the evaluation of incidence and severity of nonserious AEs and SAEs, including immune-related adverse events (irAEs), and adverse events of special interest (AESIs)
- Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Up to 24 months ]To evaluate the Tmax of XL092 alone and in combination with ICI
- Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 24 months ]To evaluate the Cmax of XL092 alone and in combination with ICI
- Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) [ Time Frame: Up to 24 months ]To evaluate the AUC 0-24 of XL092 alone and in combination with ICI
- Dose-Escalation Stage: Terminal Half-Life [ Time Frame: Up to 24 months ]To evaluate the terminal half-life of XL092 alone and in combination with ICI
- Dose-Escalation Stage: Apparent Clearance (CL/F) [ Time Frame: Up to 24 months ]To evaluate the CL/F of XL092 alone and in combination with ICI
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
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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 Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who received first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin.
- Expansion Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy.
- Expansion Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy.
- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1, with exception of Cohort I (UC, Maintenance Therapy).
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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 Criteria:
- Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, H, I, and K only), prior treatment with avelumab (Cohort J 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03845166
Contacts
| Contact: Exelixis Clinical Trials | 1-888-EXELIXIS (888-393-5494) | druginfo@exelixis.com | |
| Contact: Backup or International | 650-837-7400 |
Locations
Show 80 study locations
Sponsors and Collaborators
Exelixis
| Responsible Party: | Exelixis |
| ClinicalTrials.gov Identifier: | NCT03845166 |
| Other Study ID Numbers: |
XL092-001 2020-003569-21 ( EudraCT Number ) |
| First Posted: | February 19, 2019 Key Record Dates |
| Last Update Posted: | December 23, 2022 |
| Last Verified: | December 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Carcinoma, Renal Cell Breast Neoplasms Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Urogenital Neoplasms Neoplasms by Site Urogenital Diseases Male Urogenital Diseases Adenocarcinoma Kidney Neoplasms Urologic Neoplasms |
Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Urologic Diseases Breast Diseases Skin Diseases Atezolizumab Avelumab Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |