Stellar 303

Actively Recruiting

Phase 3 Randomized, Open-Label Study of XL092 With Atezolizumab vs Regorafenib in Metastatic Colorectal Cancer

THE COMBINATION OF XL092 AND ATEZOLIZUMAB IS NOT APPROVED FOR THE USE UNDER INVESTIGATION IN THIS TRIAL. SAFETY AND EFFICACY HAVE NOT BEEN ESTABLISHED.

  • Study Overview

  • Key Eligibility Criteria

  • Key Endpoints

  • Participating Sites

  • Resources for HCPs

Study Overview

Rationale

Microsatellite instability (MSI) is recognized as one of the major carcinogenetic pathways of colorectal cancer (CRC).1 Patients with MSI-high (MSI-H) CRC often respond to immune checkpoint inhibitors (ICI).2 However, only 4–5% of patients with metastatic CRC (mCRC) are MSI-H; most patients with mCRC are microsatellite stable (MSS) and typically do not respond to immunotherapy.2-4 Early phase studies of ICIs in combination with tyrosine kinase inhibitors have demonstrated encouraging efficacy and manageable toxicity in patients with previously treated MSS CRC,5,6 and emerging data suggest that patients without liver metastases are likely to derive the greatest benefit.7-10 This trial will assess the safety and efficacy of XL092 with atezolizumab or regorafenib monotherapy in patients with chemo-refractory mCRC who are MSS/MSI-low (MSI-L). The primary analysis will be overall survival (OS) in patients with non-liver metastases (NLM).

Design

Approximately 874 eligible patients from 140 sites globally (North America, Europe, and Asia Pacific) will be enrolled in STELLAR-303. Patients with MSS/MSI-L mCRC who have progressed during or after, or are intolerant to, standard-of-care (SOC) therapy will be randomly assigned to XL092 in combination with atezolizumab or regorafenib monotherapy to evaluate the effect of combination therapy on overall survival in patients with NLM. Eligible patients will be randomly assigned in a 1:1 ratio to each treatment arm. Approximately 350 patients with NLM will be enrolled, while enrollment of patients with liver metastases will be capped at ~524.

Chart explaining phase 3, randomized, open-label study of XL092 with atezolizumab vs regorafenib in patients with MSS/MSI-low mCRC

Key Eligibility Criteria

  • MSS/MSI-L metastatic colorectal adenocarcinoma with measurable disease

  • Known RAS status

  • Progressed, refractory, or intolerant to all of the following SOC regimens for mCRC:

    • Fluoropyrimidine, irinotecan, and oxaliplatin, ± anti-VEGF mAb

    • Anti-EGFR mAb for RASWT

    • BRAF inhibitor for known BRAF V600E mutations

  • Progression ≤4 months following the last dose of SOC regimen

  • No prior treatment with XL092, regorafenib, trifluridine/tipiracil, or PD-L1/PD-1–targeting ICIs

Key Endpoints

Primary Endpoint

  • OS in patients with NLM

Secondary Endpoints

  • OS in all patients

  • PFS by investigator

  • ORR by investigator

  • DOR by investigator

  • Safety and tolerability

Exploratory Endpoint

  • HRQoL by EORTC QLQ-C30/QLQ-CR29 and EQ-5D-5L

Participating Sites

STELLAR-303 will be conducted in North America, Europe, and Asia Pacific.

Currently open clinical sites:

Trial sites may stop enrolling patients at any time. Please check back if you do not see a trial site located near you.

Resources for Healthcare Professionals

Here you can find further information on STELLAR-303. To view information for a specific language, select it from the dropdown below.

STELLAR 303 trial infographic summary for healthcare professionals

Trial Infographic Summary

A quick snapshot of the trial

View and Download
STELLAR 303 trial healthcare professional brochure

Healthcare Professional Brochure

Find out more details about the trial

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STELLAR 303 trial brochure for patients

Patient-friendly Brochure

Use to discuss with patients who wish to enroll

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References

  1. Lee SY, et al. Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer. Medicine (Baltimore). 2015;94(50):e2260.
  2. Baraibar I, et al. Combined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer. Cancers (Basel). 2021;13(24):6311.
  3. Battaglin F, et al. Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives. Clin Adv Hematol Oncol. 2018;16(11):735-745.
  4. Fujiyoshi K, et al. Metastatic pattern of stage IV colorectal cancer with high-frequency microsatellite instability as a prognostic factor. Anticancer Res. 2017;37(1):239-247.
  5. Abrams T, et al. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; 20–22 January 2022; San Francisco, CA. Abstract 121.
  6. Saeed A, et al. Cabozantinib plus durvalumab in advanced gastroesophageal cancer and other gastrointestinal malignancies: Phase Ib CAMILLA trial results. Cell Reports Medicine. 2023;4(2):100916.
  7. Fakih MG, et al. A phase I clinical trial of regorafenib, ipilimumab, and nivolumab (RIN) in chemotherapy resistant MSS metastatic colorectal cancer (mCRC). Ann Oncol. 2022;33(Suppl 7):S684.
  8. Fakih M, et al. Regorafenib plus nivolumab in patients with mismatch repair-proficient/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study. EClinicalMedicine. 2023;58:101917.
  9. Kim RD, et al. A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer. Eur J Cancer. 2022;169:93-102.
  10. Kawazoe A, et al. Lenvatinib plus pembrolizumab versus standard of care for previously treated metastatic colorectal cancer (mCRC): the phase 3 LEAP-017 study. Ann Oncol. 2023;34(Suppl 1):S179.

BRAF, BRAF gene; CRC, colorectal cancer; DOR, duration of response; EGFR, epithelial growth factor receptor; EORTC QLQ-C30/QLQ-CR29, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30/Colorectal 29; EQ-5D-5L, EuroQol five-dimension, five-level health questionnaire instrument; HRQoL, health-related quality of life; ICI, immune checkpoint inhibitor; IV, intravenous; mAb, monoclonal antibody; mCRC, metastatic colorectal cancer; MSI, microsatellite instability; MSI-H, microsatellite instability–high; MSI-L, microsatellite instability–low; MSS, microsatellite stable; NLM, non-liver metastases; ORR, objective response rate; OS, overall survival; PD-1, programmed death receptor-1; PD-L1, programmed death receptor-1 ligand; PFS, progression-free survival; q3w, once every 3 weeks; qd, once daily; RAS, RAS gene; SOC, standard of care; VEGF, vascular endothelial growth factor; WT, wild type.

To learn more about this trial, go to clinicaltrials.gov and search for NCT05425940, or contact Exelixis Medical Information at medinfo@exelixis.com.

Links to Exelixis Website

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