Regorafenib + Pembrolizumab for Colorectal Cancer

Recruiting at 7 trial locations

Overseen By Debra Diecks, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ibrahim Halil Sahin

Must not be taking: Anti-PD-1, Anti-CTLA-4

Disqualifiers: Autoimmune disease, Uncontrolled HIV, others

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

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

154 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for a specific type of advanced colorectal cancer with a genetic trait known as MSI-H (high microsatellite instability). The goal is to evaluate the effectiveness and safety of combining Regorafenib (a cancer medication) and Pembrolizumab (an immunotherapy drug) in fighting this cancer. Suitable participants have colorectal cancer that hasn't responded to other treatments and can take oral medications. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using regorafenib and pembrolizumab together is generally safe for treating colorectal cancer. Previous studies have shown encouraging results, with the combination effectively controlling the disease in most patients.

Regorafenib alone has proven to be a safe and effective treatment for advanced colorectal cancer. Patients taking regorafenib have experienced longer survival times, indicating that the treatment is usually well-tolerated.

All treatments can have side effects. However, current evidence suggests that the combination of regorafenib and pembrolizumab is a promising and relatively safe option for colorectal cancer patients. Prospective trial participants should discuss possible side effects with a healthcare provider for more personalized information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Regorafenib for colorectal cancer because it presents a novel approach to treatment. Unlike standard care options like chemotherapy and targeted therapies, this combination leverages the immune-boosting capabilities of Pembrolizumab, a checkpoint inhibitor, alongside Regorafenib, which targets multiple kinases involved in cancer growth. This dual-action approach aims to enhance the body’s immune response while simultaneously inhibiting tumor growth pathways, offering potential for improved outcomes compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

This trial will compare the combination of pembrolizumab and regorafenib with pembrolizumab alone for treating colorectal cancer. Research has shown that using pembrolizumab and regorafenib together may aid in treating colorectal cancer. Although this combination did not significantly extend the time before cancer worsened in some studies, it led to longer survival and better disease control. Pembrolizumab is an immunotherapy that helps the immune system attack cancer cells, while regorafenib is a targeted therapy that stops cancer cells from growing. Together, they have shown promise in managing colorectal cancer and improving patient outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Anwaar H Saeed, MD

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with MSI-H colorectal cancer who can take pills and have decent organ function. They should have had limited chemotherapy, be able to use birth control, and not have other active cancers or serious health issues like uncontrolled HIV or bleeding disorders.

Inclusion Criteria

I am fully active or can carry out light work.

I am older than 18 years.

I can swallow pills.

Exclusion Criteria

I have an ongoing infection or need long-term antibiotics.

I haven't had major surgery or a serious injury recently.

I have a wound, ulcer, or bone fracture that is not healing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Phase

Participants receive regorafenib 60 mg in combination with 200 mg of pembrolizumab every 3 weeks to assess preliminary efficacy and safety

Up to 12 months

Randomized Phase

Participants are randomized to receive either pembrolizumab with regorafenib or pembrolizumab monotherapy to further examine efficacy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Regorafenib

Trial Overview The study tests Regorafenib combined with Pembrolizumab against Pembrolizumab alone in treating MSI-H colorectal cancer. It starts with a lead-in phase to check safety and early results, then moves into a randomized phase for more detailed efficacy data.

How Is the Trial Designed?

Group I: Pembrolizumab + Regorafenib Experimental Treatment 2 Interventions

Pembrolizumab: 200mg, Q3 weeks Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1

Group II: Pembrolizumab Active Control 1 Intervention

Pembrolizumab: 200mg, Q3 weeks

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

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Ibrahim Halil Sahin

Lead Sponsor

Trials

2

Recruited

150+

Anwaar Saeed

Lead Sponsor

Trials

5

Recruited

240+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a study of 23 patients with metastatic colorectal cancer who had previously undergone multiple treatments, regorafenib showed some efficacy, with 34.8% achieving stable disease and 8.7% showing partial response, although 56.5% experienced disease progression.

Regorafenib treatment was associated with significant side effects, with 65% of patients experiencing severe toxicity, primarily hand-foot syndrome and fatigue, leading to dose reductions in 86.9% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and early outcomes of regorafenib in multiply pre-treated metastatic colorectal adenocarcinoma-experience from a tertiary cancer centre in India. Zanwar, S., Ostwal, V., Gupta, S., et al.[2022]

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 of 72 patients with microsatellite stable metastatic colorectal cancer, regorafenib or fruquintinib combined with sintilimab showed a median progression-free survival of 4.2 months and an overall survival of 10.5 months, indicating these combinations are viable third-line treatment options.

The treatment was generally well-tolerated, with only 15.3% of patients experiencing severe adverse events, and patients without liver metastasis showed better response rates and overall survival, suggesting they may benefit more from this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. Nie, C., Lv, H., Chen, B., et al.[2022]

In a phase II trial involving 48 patients with microsatellite stable colorectal cancer, the combination of regorafenib and avelumab showed a best response of stable disease in 53.5% of patients, with a median progression-free survival of 3.6 months and overall survival of 10.8 months.

The study found that higher infiltration of CD8+ T cells in tumors was linked to better outcomes, suggesting that assessing immune cell presence could help identify patients who might benefit more from this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib-Avelumab Combination in Patients with Microsatellite Stable Colorectal Cancer (REGOMUNE): A Single-arm, Open-label, Phase II Trial. Cousin, S., Cantarel, C., Guegan, JP., et al.[2022]

Regorafenib, a multikinase inhibitor used for advanced solid tumors, was associated with a range of adverse events (AEs) in a meta-analysis of 2,065 patients, with the most common being hand-foot skin reaction (54%), diarrhea (33%), and fatigue (32%).

The analysis revealed that regorafenib significantly increases the risk of developing AEs compared to placebo, highlighting the importance of monitoring these effects to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. Yin, X., Yin, Y., Shen, C., et al.[2022]

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

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 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]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Regorafenib has shown statistically significant improvements in overall survival, progression-free survival, and disease control in patients with metastatic colorectal cancer, based on results from two phase III trials (CORRECT and CONCUR) and two real-world studies (REBECCA and CONSIGN).

Despite these positive outcomes, there are concerns that the clinical benefits of regorafenib may not be meaningful for all patients, and some subgroups may not experience the same level of benefit, highlighting the need for further investigation into its efficacy across different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is regorafenib providing clinically meaningful benefits to pretreated patients with metastatic colorectal cancer? García-Alfonso, P., Feliú, J., García-Carbonero, R., et al.[2018]

Citations

1. cancernetwork.com cancernetwork.com/view/regorafenib-plus-pembrolizumab-combo-misses-pfs-end-point-shows-strong-os-for-mss-colorectal-cancer

Regorafenib Plus Pembrolizumab Combo Misses PFS ... Combining pembrolizumab (Keytruda) with regorafenib (Stivarga) resulted in promising median overall survival (OS) and duration of disease control.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03657641

Regorafenib and Pembrolizumab in Treating Participants ... This phase I/II studies the side effects and best dose of regorafenib when given together with pembrolizumab in treating participants with colorectal cancer ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11231874/

Efficacy and safety of regorafenib in the treatment ... The mCRC patients who received a third-line regorafenib treatment demonstrated a median overall survival (mOS) of 8.8 months and a median ...

4. onclive.com onclive.com/view/regorafenib-pembrolizumab-misses-pfs-end-point-in-mss-crc-but-biomarker-analyses-are-ongoing

Regorafenib/Pembrolizumab Misses PFS End Point in ... The combination of regorafenib (Stivarga) and pembrolizumab (Keytruda) failed to significantly improve progression-free survival (PFS) in patients with ...

5. journalofoncology.org journalofoncology.org/articles/is-the-combination-of-pembrolizumab-and-regorafenib-the-beginning-of-a-new-era-in-the-treatment-of-metastatic-colorectal-cancer/jos.galenos.2025.2025-3-23

Is the Combination of Pembrolizumab and Regorafenib ... An ongoing phase II trial (NCT06006923) is evaluating the safety and efficacy of regorafenib combined with pembrolizumab in MSIH colorectal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7689210/

The Efficacy and Safety of Regorafenib in Combination ... The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of ...