What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as PD-L1 inhibitors (e.g., atezolizumab) and multi-kinase inhibitors (e.g., regorafenib), have distinct side effect profiles. Atezolizumab can cause immune-related adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Regorafenib is associated with hand-foot skin reactions, hypertension, fatigue, diarrhea, and hepatotoxicity. Both treatments can lead to general side effects like fatigue, decreased appetite, and gastrointestinal disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer that are similar to those being studied in the trial XL092 + atezolizumab vs regorafenib. Atezolizumab, a PD-L1 inhibitor, is being explored in combination with other agents for its potential benefits in colorectal cancer. Regorafenib, a multi-kinase inhibitor, has already been approved for the treatment of metastatic colorectal cancer in patients who have progressed after standard therapies. Other similar FDA-approved treatments include nivolumab (a PD-1 inhibitor) and pembrolizumab (another PD-1 inhibitor), which have shown efficacy in certain subsets of colorectal cancer patients, particularly those with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR).

What other types of research exist?

Promising novel alternatives for colorectal cancer treatment in 2024 include: 1) Nivolumab plus relatlimab, which targets PD-1 and LAG-3, showing efficacy in other cancers and potential in colorectal cancer. 2) Pembrolizumab (PD-1 inhibitor) combined with lenvatinib (multi-kinase inhibitor), which has shown promise in other solid tumors. 3) Enfortumab vedotin, an antibody-drug conjugate, which is being explored in various cancers and may offer benefits in colorectal cancer. These alternatives are based on their mechanisms of action and recent clinical trial results.

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PD-L1 Inhibitor

XL092 + Atezolizumab vs Regorafenib for Colorectal Cancer (STELLAR-303 Trial)

Phase 3

Waitlist Available

Research Sponsored by Exelixis

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization

Female subjects of childbearing potential must not be pregnant at screening

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 26 months after the first subject is randomized.

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a combination of two drugs, XL092 and atezolizumab, against another treatment in patients with a specific type of colorectal cancer that has spread and not responded to standard treatments. The goal is to see if the new combination can better stop cancer growth and help the immune system fight the cancer.

Who is the study for?

Adults with metastatic colorectal cancer that's not highly unstable at the genetic level (MSS/MSI-low) can join if they've had progression after standard treatments. They need a confirmed diagnosis, RAS status known, and must have recovered from previous treatment side effects to a mild level. They should be relatively fit (ECOG 0-1), have measurable disease, and provide tumor biopsy material.

What is being tested?

The trial is testing XL092 in combination with Atezolizumab against Regorafenib alone in patients whose colorectal cancer has worsened despite standard care. It's randomized and open-label, meaning participants know which treatment they're getting.

What are the potential side effects?

Possible side effects include fatigue, diarrhea, high blood pressure for Regorafenib; while XL092 + Atezolizumab may cause immune-related reactions like rash or liver inflammation, infusion reactions, tiredness and loss of appetite.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can provide a sample of my tumor, either from previous or new biopsies.

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I am not pregnant.

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I am receiving the standard cancer treatment available in my country.

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My metastatic colorectal cancer has worsened or not responded to standard treatments.

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My colorectal cancer is not MSI-high or dMMR based on tissue tests.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My cancer's RAS status has been tested.

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My cancer is confirmed as colon or rectum adenocarcinoma.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken any cancer-targeting pill treatments in the last 2 weeks.

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I haven't had cancer treatments like chemotherapy or hormone therapy in the last 3 weeks.

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I have not had major surgery in the last 4 weeks.

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I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

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I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

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I have a serious illness that is not under control.

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I have previously been treated with XL092, regorafenib, trifluridine/tipiracil, or drugs targeting PD-L1/PD-1.

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I cannot swallow pills or receive IV treatments, or I have a stomach condition affecting drug absorption.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 26 months after the first subject is randomized.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 26 months after the first subject is randomized.

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 26 months after the first subject is randomized. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival

Other study objectives

Duration of Response (DOR) as assessed by the Investigator per RECIST 1.1

Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1

Progression-Free Survival (PFS) as assessed by the Investigator per RECIST 1.1

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Experimental ArmExperimental Treatment2 Interventions

Subjects with mCRC will receive XL092 + atezolizumab

Group II: Control ArmActive Control1 Intervention

Subjects with mCRC will receive active comparator of regorafenib

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Colorectal cancer treatments often target specific pathways to inhibit tumor growth and spread. Atezolizumab, a PD-L1 inhibitor, works by blocking the interaction between PD-L1 on tumor cells and PD-1 on immune cells, thereby enhancing the immune system's ability to attack cancer cells. Regorafenib, a multi-kinase inhibitor, targets multiple protein kinases involved in tumor angiogenesis, oncogenesis, and the tumor microenvironment, effectively inhibiting tumor growth and metastasis. These mechanisms are crucial for colorectal cancer patients as they offer targeted approaches to disrupt cancer progression and improve survival outcomes.