XL092 + Atezolizumab vs Regorafenib for Colorectal Cancer

(STELLAR-303 Trial)

Recruiting at 145 trial locations

Overseen By Backup or International

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Exelixis

Must not be taking: Corticosteroids, Immunosuppressives, Kinase inhibitors, others

Disqualifiers: Brain metastases, Uncontrolled illness, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

874 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not have taken a small molecule kinase inhibitor within 2 weeks, anticancer antibody therapy or systemic chemotherapy within 3 weeks, or bevacizumab within 4 weeks before joining the trial.

What data supports the effectiveness of the drug regorafenib for colorectal cancer?

Regorafenib has been shown to improve survival in patients with metastatic colorectal cancer who have already tried other treatments. Studies found that it can extend overall survival and progression-free survival compared to a placebo, making it a valuable option for patients with limited treatment choices. ^{1 2 3 4 5}

What is known about the safety of Regorafenib in humans?

Regorafenib is generally considered safe for humans, with most side effects being mild to moderate, such as skin reactions and increased liver enzymes. However, more serious side effects like hand-foot syndrome, diarrhea, high blood pressure, and fatigue have been reported, especially in patients with liver issues. ^{2 4 6 7 8}

How is the drug combination of XL092 and Atezolizumab different from Regorafenib for colorectal cancer?

The combination of XL092 and Atezolizumab is being tested as a new approach for colorectal cancer, potentially offering a different mechanism of action compared to Regorafenib, which is a multikinase inhibitor targeting various pathways involved in tumor growth. This trial explores whether combining these drugs can provide better outcomes than using Regorafenib alone, which is already approved for use after standard therapies have failed. ^{1 9 10 11 12}

Eligibility Criteria

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.

Inclusion Criteria

My cancer has worsened during or within 4 months after my last standard chemotherapy.

Measurable disease according to RECIST v1.1 as determined by the Investigator

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

Exclusion Criteria

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

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

My brain metastases have been treated and stable for over 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either XL092 + atezolizumab or regorafenib

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

Treatment Details

Interventions

• Atezolizumab
• Regorafenib
• XL092

Trial Overview 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.

Participant Groups

Group I: Experimental Arm Experimental Treatment 2 Interventions

Subjects with mCRC will receive XL092 + atezolizumab

Group II: Control Arm Active Control 1 Intervention

Subjects with mCRC will receive active comparator of regorafenib

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

A phase III study found that the combination of atezolizumab and cobimetinib did not show improved effectiveness compared to standard therapy (regorafenib) in patients with inoperable, locally advanced, or metastatic colorectal cancer.

The overall survival for patients receiving the combination treatment was 8.9 months, slightly higher than the 8.5 months for those on standard therapy, but the response rates were very similar at 2.7% for the combination versus 2.2% for regorafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Duo Disappoints in Colorectal Cancer. [2019]

Regorafenib significantly improves median overall survival and progression-free survival in patients with previously treated metastatic colorectal cancer (mCRC), as shown in the CORRECT trial with a regimen of 160 mg daily for 3 weeks of each 4-week cycle.

The drug has a generally acceptable tolerability profile and does not compromise health-related quality of life, making it a valuable addition to treatment options for patients with progressive mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib: a review of its use in previously treated patients with progressive metastatic colorectal cancer. Carter, NJ.[2021]

Regorafenib significantly improves overall survival by up to 2.5 months and progression-free survival by up to 1.5 months in patients with metastatic colorectal cancer (mCRC) who have not responded to standard therapies, based on phase 3 studies.

The treatment is generally well-tolerated, with most side effects being mild to moderate, and it does not negatively impact health-related quality of life compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib: A Review in Metastatic Colorectal Cancer. Dhillon, S.[2019]

In a study involving patients with metastatic colorectal cancer, prophylactic oral dexamethasone (DEX) showed a trend towards reducing the incidence of grade ≥2 fatigue and malaise compared to placebo, with 19.4% in the DEX group versus 38.9% in the placebo group.

Although the overall incidence of fatigue and malaise was similar between the DEX and placebo groups, patient-reported outcomes indicated a significant reduction in fatigue with DEX, suggesting it may be clinically effective in managing regorafenib-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402). Tanioka, H., Miyamoto, Y., Tsuji, A., et al.[2018]

Regorafenib is an effective treatment for patients with metastatic colorectal cancer who have previously undergone multiple chemotherapy regimens, showing a significant improvement in overall survival compared to placebo (6.4 months vs 4 months).

The treatment is associated with manageable side effects, with the most common severe adverse events being hand-foot syndrome (17%) and asthenia (10%), indicating that while it is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Regorafenib approved in Metastatic Colorectal cancer]. André, T., Dumont, SN.[2022]

Regorafenib is an effective oral multikinase inhibitor approved by the FDA for treating metastatic colorectal cancer in patients who have not responded to standard chemotherapy and other targeted therapies, showing significant efficacy compared to placebo in the CORRECT trial.

While regorafenib has a greater antiangiogenic effect than sorafenib, it is associated with common severe side effects such as hand-foot skin reactions, diarrhea, hypertension, and fatigue, which require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of regorafenib-related toxicities: a review. Krishnamoorthy, SK., Relias, V., Sebastian, S., et al.[2022]

Regorafenib is an FDA-approved oral medication that targets multiple kinases involved in cancer growth and has shown survival benefits in patients with metastatic colorectal cancer after standard treatments have failed.

In addition to colorectal cancer, regorafenib significantly improves progression-free survival in patients with metastatic gastrointestinal stromal tumors (GIST) and is currently being tested in various other cancers, including renal cell carcinoma and hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Drug Duo Disappoints in Colorectal Cancer. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Regorafenib: a review of its use in previously treated patients with progressive metastatic colorectal cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Regorafenib: A Review in Metastatic Colorectal Cancer. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402). [2018]

6. France pubmed.ncbi.nlm.nih.gov

[Regorafenib approved in Metastatic Colorectal cancer]. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Management of regorafenib-related toxicities: a review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic colorectal cancer patient with liver dysfunction: A case report. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Sequential Treatment With Trifluridine/Tipiracil and Regorafenib in Refractory Metastatic Colorectal Cancer Patients: An AGEO Prospective "Real-World Study". [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2015]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Survival Benefit of Crossover Administration of Regorafenib and Trifluridine/Tipiracil Hydrochloride for Patients With Metastatic Colorectal Cancer: Exploratory Analysis of a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study (REGOTAS). [2021]

12. Greece pubmed.ncbi.nlm.nih.gov

Clinical Outcomes Following Trifluridine/Tipiracil Treatment for Patients With Metastatic Colorectal Cancer Ineligible for Regorafenib Treatment. [2021]