Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)
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| ClinicalTrials.gov Identifier: NCT05176483 |
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Recruitment Status :
Recruiting
First Posted : January 4, 2022
Last Update Posted : April 2, 2024
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Sponsor:
Exelixis
Information provided by (Responsible Party):
Exelixis
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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 + relatlimab (triplet) in subjects with advanced solid tumors.
In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Cell Carcinoma Metastatic Castration-resistant Prostate Cancer Urothelial Carcinoma Solid Tumor Hepatocellular Carcinoma Non-small Cell Lung Cancer Colorectal Cancer Head and Neck Squamous Cell Carcinoma | Drug: XL092 Drug: Nivolumab Drug: Ipilimumab Drug: Nivolumab + Relatlimab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1078 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Dose-escalation followed by expansion phase with parallel assignment. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | December 14, 2021 |
| Estimated Primary Completion Date : | February 2026 |
| Estimated Study Completion Date : | May 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Head and neck squamous cell carcinoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: XL092 + Nivolumab Dose-Escalation Cohorts
Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
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Drug: XL092
XL092 orally once daily (qd) Drug: Nivolumab 360 mg IV infusion once every 3 weeks (q3w)
Other Name: Opdivo |
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Experimental: XL092 + Nivolumab + Ipilimumab Dose-Escalation Cohorts
Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
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Drug: XL092
XL092 orally once daily (qd) Drug: Ipilimumab 1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
Other Name: Yervoy Drug: Nivolumab 3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
Other Name: Opdivo |
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Experimental: XL092 + Nivolumab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
|
Drug: XL092
XL092 orally once daily (qd) Drug: Nivolumab 480 mg IV infusion once every 4 weeks (q4w)
Other Name: Opdivo |
|
Experimental: XL092 + Nivolumab + Ipilimumab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
|
Drug: XL092
XL092 orally once daily (qd) Drug: Ipilimumab 1 mg/kg IV infusion once every 3 weeks (q3w) for maximum of four doses
Other Name: Yervoy Drug: Nivolumab 3 mg/kg IV infusion once every 3 weeks (q3w) for first four doses, and then 480 mg IV infusion once every 4 weeks (q4w)
Other Name: Opdivo |
| Experimental: XL092 Single-Agent Expansion Cohorts |
Drug: XL092
XL092 orally once daily (qd) |
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Experimental: XL092 + Nivolumab + Relatlimab 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 + Relatlimab IV administration of nivolumab + relatlimab |
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Experimental: XL092 + Nivolumab + Relatlimab Expansion Cohorts
The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
|
Drug: XL092
XL092 orally once daily (qd) Drug: Nivolumab + Relatlimab IV administration of nivolumab + relatlimab |
Primary Outcome Measures :
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including immune-mediated adverse events (imAEs) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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)
- Expansion Stage: Overall Survival (OS) [ Time Frame: 6 months ]For Cohort 10 (CRC): Overall Survival (OS) rate
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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 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.
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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.
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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.
- Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
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Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
- Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
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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.
- Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
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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, maintenance therapy or adjuvant therapy.
- Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.
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Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.
- 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 Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.
- Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
- Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
- Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
- Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
- For all Expansion Cohorts except Cohort 3: 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:
- For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).
- For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): 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 all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
- Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
- Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
- 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.
- Administration of a live, attenuated vaccine within 30 days prior to enrollment.
- 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.
- Subjects with inadequately treated adrenal insufficiency.
- 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.
- For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
- For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
- For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
- For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
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For Cohort 7 (HCC):
- Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).
- Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
- Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.
- Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
- For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.
- For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
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For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):
- Troponin T (TnT) or I (TnI) > 2 × institutional ULN.
Note: Additional Inclusion and Exclusion criteria may apply.
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): NCT05176483
Contacts
| Contact: Exelixis Clinical Trials | 1-888-EXELIXIS (888-393-5494) | druginfo@exelixis.com | |
| Contact: Backup or International | 650-837-7400 |
Locations
Show 122 study locations
Sponsors and Collaborators
Exelixis
| Responsible Party: | Exelixis |
| ClinicalTrials.gov Identifier: | NCT05176483 |
| Other Study ID Numbers: |
XL092-002 |
| First Posted: | January 4, 2022 Key Record Dates |
| Last Update Posted: | April 2, 2024 |
| Last Verified: | April 2024 |
| 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 Squamous Cell Carcinoma of Head and Neck Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Urogenital Neoplasms Neoplasms by Site Urogenital Diseases Male Urogenital Diseases Carcinoma, Squamous Cell Adenocarcinoma Kidney Neoplasms |
Urologic Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Urologic Diseases Head and Neck Neoplasms Nivolumab Ipilimumab Relatlimab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |