What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as Regorafenib (a multi-kinase inhibitor) and XmAb20717 (an immune checkpoint inhibitor), have known side effects. Regorafenib can cause diarrhea, fatigue, hypertension, hand-foot skin reactions, and liver toxicity. XmAb20717 may lead to immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. These side effects are typical of multi-kinase inhibitors and immune checkpoint inhibitors used in colorectal cancer treatment.

What prior FDA approvals exist?

Regorafenib, a multi-kinase inhibitor, was approved by the FDA for the treatment of metastatic colorectal cancer in patients who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy. Another relevant drug is pembrolizumab, an immune checkpoint inhibitor targeting PD-1, which has been approved for use in colorectal cancer with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. These approvals highlight the FDA's recognition of both multi-kinase inhibitors and immune checkpoint inhibitors as viable treatments for colorectal cancer.

What other types of research exist?

Promising novel alternatives for colorectal cancer treatment in 2024 include: 1) Trifluridine/tipiracil (TAS-102), a combination of a nucleoside analog and a thymidine phosphorylase inhibitor, which has shown efficacy in metastatic colorectal cancer. 2) Encorafenib combined with cetuximab, particularly for patients with BRAF V600E-mutant metastatic colorectal cancer. 3) Pembrolizumab, an anti-PD-1 therapy, for patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer. 4) Nivolumab plus ipilimumab, another combination of immune checkpoint inhibitors, for MSI-H or dMMR colorectal cancer. These alternatives offer different mechanisms of action and have demonstrated promising results in clinical settings.

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Tyrosine Kinase Inhibitor

Regorafenib + XmAb20717 for Colorectal Cancer

Phase 2

Waitlist Available

Led By Kanwal Raghav, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Histological confirmation of CRC

Post-R0 resection of stages II, III, or IV CRC and all planned adjuvant therapies have been completed

Must not have

Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for mCRC.

Previous malignant disease (other than the target malignancy to be investigated in this trial) within 3 years prior to study treatment initiation.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, regorafenib and vudalimab, in colorectal cancer patients who have completed standard treatment but still have small amounts of cancer detectable in their blood. Regorafenib helps slow down cancer growth, while vudalimab boosts the immune system to attack cancer cells. The goal is to see if this combination can clear the remaining cancer and improve patient outcomes.

Who is the study for?

This trial is for adults over 18 with colorectal cancer who've had surgery to remove their tumor and finished any other treatments. They must have signs of microscopic cancer left, as shown by a ctDNA test, good organ function, no recent major surgeries or serious illnesses, and not be on immunosuppressants. Women who can get pregnant and men must agree to use birth control during the study.

What is being tested?

The trial tests Regorafenib and XmAb20717 (vudalimab) in patients with high-risk colorectal cancer showing no visible tumors but positive for ctDNA. The goal is to see if these drugs can reduce or eliminate this molecular residual disease after six months of treatment.

What are the potential side effects?

Possible side effects include fatigue, high blood pressure, hand-foot skin reactions from Regorafenib; immune-related issues like inflammation in organs due to XmAb20717 could also occur. Both drugs may cause liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

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

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My colorectal cancer has been confirmed through tissue examination.

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I've completed all treatments after surgery for stage II-IV colon cancer.

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My kidney function, measured by creatinine clearance, is sufficient.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

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I have not had a menstrual period for at least 12 months.

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I have had a hysterectomy or both ovaries removed.

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I have ovarian failure due to radiation therapy.

Exclusion Criteria

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

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I have previously been treated with drugs that boost the immune system to fight my colorectal cancer.

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I have not had any other cancer besides the one being studied in the last 3 years.

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I have an autoimmune disease that could worsen with immune-boosting treatments.

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I have severe allergies to certain medications or uncontrolled asthma recently.

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I have recovered from previous cancer treatment side effects, except for immune-related ones, to a mild level.

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I have had lung inflammation treated with steroids or have a lung condition.

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I do not have severe protein leakage in my urine.

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My blood pressure is very high (over 160/100).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Regorafenib and XmAb20717Experimental Treatment2 Interventions

Participants will receive regorafenib and XmAb20717 for up to 6 cycles (6 months). Participants will take regorafenib by mouth on Days 1-21 of each cycle. Participants will rest (not take regorafenib) on Days 21-28 of each cycle. Participants will also receive XmAb20717 by vein on Days 1 and 15 of each cycle. Each infusion should take about 60 minutes.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Regorafenib

2014

Completed Phase 2

~1600

XmAb20717

2018

Completed Phase 1

~150

0 / 16Eligibility 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

The most common treatments for colorectal cancer include multi-kinase inhibitors and immune checkpoint inhibitors. Regorafenib, a multi-kinase inhibitor, works by blocking multiple protein kinases involved in tumor growth, angiogenesis, and the tumor microenvironment, thereby inhibiting cancer cell proliferation and survival. XmAb20717, an immune checkpoint inhibitor, targets and blocks proteins like PD-1 and CTLA-4 that cancer cells use to evade the immune system, thus enhancing the body's immune response against cancer cells. These treatments are crucial for colorectal cancer patients as they offer targeted approaches to control tumor growth and improve survival outcomes, especially in cases where traditional therapies have failed.