Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer (STELLAR-303)

• ClinicalTrials.gov Identifier: NCT05425940
• Recruitment Status: Recruiting
• First Posted: June 21, 2022
• Last Update Posted: March 19, 2024
• Sponsor: Exelixis
• Information provided by (Responsible Party): Exelixis

Tracking Information

• First Submitted Date: June 16, 2022
• First Posted Date: June 21, 2022
• Last Update Posted Date: March 19, 2024
• Actual Study Start Date: September 7, 2022
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2024)

Overall Survival [ Time Frame: Approximately 32 months after the first subject is randomized. ]

The primary objective of this study is to evaluate OS of XL092 + atezolizumab versus regorafenib in non-liver metastases (NLM) subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy. Subjects without liver metastases (NLM) are defined as subjects without active liver metastases at screening as determined on baseline imaging of the liver as performed by CT scan with contrast or MRI. Definitively treated liver metastases (which includes surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) that were treated at least 6 months prior to enrollment with no evidence of radiologic progression on subsequent imaging are considered to be non-active liver metastases.

Original Primary Outcome Measures (submitted: June 16, 2022)

Duration of Overall Survival (OS) [ Time Frame: Approximately 26 months after the first subject is randomized ]

Defined as the time from randomization to death due to any cause

Current Secondary Outcome Measures (submitted: January 18, 2024)

Overall Survival [ Time Frame: Approximately 32 months after the first subject is randomized. ]

The key secondary objective is to evaluate OS of XL092 + atezolizumab versus regorafenib in all randomized subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: January 18, 2024)

• Progression-Free Survival (PFS) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Approximately 26 months after the first subject is randomized. ]
  Defined as the time randomization to the earlier of either radiographic progressive disease (PD) as assessed by the Investigator per RECIST 1.1 or death from any cause.
• Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Up to 36 months after the first subject is randomized. ]
  Defined as the proportion of subjects experiencing a confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator per RECIST 1.1 criteria.
• Duration of Response (DOR) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Up to 36 months after the first subject is randomized. ]
  Defined as the time from the first documentation of objective response (subsequently confirmed at a visit ≥ 28 days later) to either radiographic disease progression or death due to any cause.

Original Other Pre-specified Outcome Measures (submitted: June 16, 2022)

• Duration of Progression-Free Survival (PFS) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Collected at selected time points (eg, 6 months and 12 months) ]
  Defined as the time randomization to the earlier of either radiographic PD as assessed by the Investigator per RECIST 1.1 or death from any cause
• Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Up to 36 months after the first subject is randomized ]
  Defined as the proportion of subjects experiencing a confirmed complete response (CR) or confirmed partial response (PR) per as assessed by the Investigator RECIST 1.1 criteria
• Duration of Response (DOR) as assessed by the Investigator per RECIST 1.1 [ Time Frame: Up to 36 months after the first subject is randomized ]
  Defined as the time from the first documentation of objective response (subsequently confirmed at a visit ≥ 28 days later) to disease progression or death due to any cause

Descriptive Information

• Brief Title: Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
• Official Title: A Randomized Open-Label Phase 3 Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
• Brief Summary: This is a multicenter, randomized, open-label, controlled Phase 3 trial of XL092 + atezolizumab vs regorafenib in subjects with microsatellite stable/microsatellite instability low (MSS/MSI-low) metastatic colorectal cancer (mCRC) who have progressed during, after or are intolerant to standard-of-care (SOC) therapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: XL092
  Supplied as tablets; administered orally daily
• Drug: Atezolizumab
  Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once in a 3-week cycle (q3w)
  Other Name: Tecentriq®
• Drug: Regorafenib
  Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle
  Other Name: Stivarga®

Study Arms

• Experimental: Experimental Arm
  Subjects with mCRC will receive XL092 + atezolizumab
  Interventions:

  • Drug: XL092
  • Drug: Atezolizumab
• Active Comparator: Control Arm
  Subjects with mCRC will receive active comparator of regorafenib
  Intervention: Drug: Regorafenib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 18, 2024): 874
• Original Estimated Enrollment (submitted: June 16, 2022): 600
• Estimated Study Completion Date: February 2026
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects with histologically or cytologically confirmed adenocarcinoma of the colon or rectum.

  • Documented RAS status (mutant or wild-type [WT]), by tissue-based analysis.
  • Documented NOT to have microsatellite instability-high (MSI-high) or mismatch repair deficient (dMMR) CRC by tissue-based analysis.

• Has received standard-of-care (SOC) anticancer therapies as prior therapy for metastatic CRC and has radiographically progressed, is refractory or intolerant to these therapies.

  • Systemic SOC anticancer therapy if approved and available in the country where the subject is randomized.
  • Radiographic progression during treatment with or within 4 months following the last dose of the most recent approved SOC chemotherapy regimen.
• Measurable disease according to RECIST v1.1 as determined by the Investigator.
• Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.
• Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Age 18 years or older on the day of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ and marrow function.
• Fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and after the last dose of treatment.
• Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria:

• Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 targeting immune checkpoint inhibitors (ICIs).
• Receipt of a small molecule kinase inhibitor (including investigational agents) within 2 weeks before randomization.
• Receipt of any type of anticancer antibody therapy, systemic chemotherapy, or hormonal anti-cancer therapy within 3 weeks (or bevacizumab within 4 weeks) before randomization.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before randomization.
• 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 randomization.
• Subject has uncontrolled, significant intercurrent or recent illness.
• Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization.
• Systemic treatment with, or any condition requiring, either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days before randomization.
• History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
• Pregnant or lactating females.
• Inability to swallow study treatment formulation, inability to receive IV administration, or presence of GI condition that might affect the absorption of study drug.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Any other active malignancy or diagnosis of another malignancy within 2 years before randomization. Exceptions are noted in the protocol.
• Administration of a live, attenuated vaccine within 30 days before randomization.

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, Belgium, France, Germany, Hong Kong, Hungary, Korea, Republic of, New Zealand, Poland, Portugal, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT05425940
• Other Study ID Numbers: XL092-303; 2021-003243-21 ( EudraCT Number )
• 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

• Plan to Share IPD: No

• 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: March 2024