Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)

• ClinicalTrials.gov Identifier: NCT05176483
• Recruitment Status: Recruiting
• First Posted: January 4, 2022
• Last Update Posted: April 2, 2024
• Sponsor: Exelixis
• Information provided by (Responsible Party): Exelixis

Tracking Information

• First Submitted Date: December 15, 2021
• First Posted Date: January 4, 2022
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: December 14, 2021
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2023)

• 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

Original Primary Outcome Measures (submitted: December 15, 2021)

• 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)

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 + 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

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

Condition

• 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

Intervention

• Drug: XL092
  XL092 orally once daily (qd)
• Drug: Nivolumab
  360 mg IV infusion once every 3 weeks (q3w)
  Other Name: Opdivo
• 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
• Drug: Nivolumab
  480 mg IV infusion once every 4 weeks (q4w)
  Other Name: Opdivo
• Drug: Nivolumab + Relatlimab
  IV administration of nivolumab + relatlimab

Study Arms

• Experimental: XL092 + Nivolumab Dose-Escalation Cohorts
  Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
  Interventions:

  • Drug: XL092
  • Drug: Nivolumab
• Experimental: XL092 + Nivolumab + Ipilimumab Dose-Escalation Cohorts
  Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
  Interventions:

  • Drug: XL092
  • Drug: Ipilimumab
  • Drug: Nivolumab
• Experimental: XL092 + Nivolumab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
  Interventions:

  • Drug: XL092
  • Drug: Nivolumab
• Experimental: XL092 + Nivolumab + Ipilimumab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
  Interventions:

  • Drug: XL092
  • Drug: Ipilimumab
  • Drug: Nivolumab
• Experimental: XL092 Single-Agent Expansion Cohorts
  Intervention: Drug: XL092
• Experimental: XL092 + Nivolumab + Relatlimab Dose-Escalation Cohorts
  Approximately 12 subjects will accrue across 1-2 dose levels of XL092 following the "rolling 6" design.
  Interventions:

  • Drug: XL092
  • Drug: Nivolumab + Relatlimab
• Experimental: XL092 + Nivolumab + Relatlimab Expansion Cohorts
  The recommended dose from the dose-escalation stage may be further explored in tumor-specific cohorts.
  Interventions:

  • Drug: XL092
  • Drug: Nivolumab + Relatlimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2023): 1078
• Original Estimated Enrollment (submitted: December 15, 2021): 826
• Estimated Study Completion Date: May 2026
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

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.
  • Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Exelixis Clinical Trials; 1-888-EXELIXIS (888-393-5494); druginfo@exelixis.com

Contact: Backup or International; 650-837-7400

• Listed Location Countries: Australia, Austria, Belgium, France, Germany, Israel, Italy, New Zealand, Poland, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT05176483
• Other Study ID Numbers: XL092-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Exelixis
• Original Responsible Party: Same as current
• Current Study Sponsor: Exelixis
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Exelixis
• Verification Date: April 2024