What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as regorafenib and pembrolizumab, have distinct side effect profiles. Regorafenib often causes hand-foot skin reactions, diarrhea, hypertension, fatigue, and liver toxicity. Pembrolizumab, on the other hand, can lead to immune-related adverse effects including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Regorafenib, a multi-kinase inhibitor, has been FDA-approved for the treatment of metastatic colorectal cancer in patients who have previously been treated with chemotherapy, anti-VEGF therapy, and anti-EGFR therapy. Pembrolizumab, a PD-1 inhibitor, has also received FDA approval for the treatment of microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer in patients who have progressed following standard treatments. These approvals highlight the use of targeted therapies and immunotherapies in managing advanced colorectal cancer.

What other types of research exist?

Promising novel alternatives for colorectal cancer treatment in 2024 include Enfortumab Vedotin, a Nectin-4 targeting antibody-drug conjugate, and Atezolizumab, a PD-L1 inhibitor. Additionally, combination therapies such as Nivolumab plus Ipilimumab (dual checkpoint blockade) and personalized antibody treatments like those evaluated in the PANGEA study are emerging as effective options.

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PD-1 Inhibitor

Regorafenib + Pembrolizumab for Colorectal Cancer

Phase 1 & 2

Waitlist Available

Led By Heinz-Josef Lenz, MD

Research Sponsored by University of Southern California

Eligibility Criteria Checklist

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

Must have

Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Patients with histologically or cytologically confirmed advanced or metastatic colorectal cancer who had failed or are intolerant of oxaliplatin, irinotecan, and fluorouracil (5-FU)

Must not have

Patients with a seizure disorder who require pharmacotherapy

Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (>= grade 3, NCI-CTCAE version [v] 4.0)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 months after study entry

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a combination of regorafenib and pembrolizumab in patients with advanced colorectal cancer. Regorafenib directly attacks cancer cells, and pembrolizumab helps the immune system fight the cancer.

Who is the study for?

This trial is for adults with advanced or metastatic colorectal cancer who have not responded to standard treatments. They must be able to take oral medication, have certain blood and liver function levels within specific ranges, and agree to use contraception during and after the trial. Those with severe heart conditions, uncontrolled hypertension, active infections or autoimmune diseases are excluded.

What is being tested?

The study is testing the combination of two drugs: Regorafenib (a chemotherapy drug) and Pembrolizumab (an immunotherapy monoclonal antibody). The goal is to find out if this combo is more effective in stopping the growth or spread of colorectal cancer cells compared to current treatments.

What are the potential side effects?

Possible side effects include fatigue, skin reactions, diarrhea, increased blood pressure from Regorafenib; immune-related issues like inflammation in organs or infusion reactions from Pembrolizumab. Each patient's experience may vary.

Eligibility Criteria

Inclusion Criteria

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

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

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My colorectal cancer is advanced, and I can't tolerate standard treatments.

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I agree to use contraception for 31 weeks after my last dose of the study drug.

Exclusion Criteria

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

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I take medication to control my seizures.

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My urine test shows high protein levels.

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I haven't had severe bleeding in the last 4 weeks.

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I haven't received any live vaccines in the last 30 days and won't during the trial.

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I have brain metastasis causing symptoms.

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I am not pregnant, breastfeeding, or planning to become pregnant.

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I am not receiving any cancer treatments other than regorafenib and pembrolizumab.

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My high blood pressure is hard to control even with multiple medications.

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I haven't had major surgery or a serious injury in the last 28 days.

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I have a history of bleeding disorders, regardless of severity.

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I do not have active hepatitis B.

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I am not on long-term steroids or immunosuppressants, nor have I taken them in the last 14 days.

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

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I am not currently on, nor have I recently taken, any excluded medications.

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I have severe heart failure.

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I have taken regorafenib in the past.

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I need drainage for fluid in my chest or abdomen more than once a week.

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I have a blockage in my digestive tract.

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I have active symptoms of interstitial lung disease.

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I have tested positive for HIV, HTLV-1, hepatitis B, or hepatitis C.

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I do not have a severe infection right now.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 months after study entry

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 months after study entry

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 months after study entry for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicity (DLTs) (Phase I)

Overall survival (OS)

Progression-free survival (PFS) (Phase II)

Side effects data

From 2019 Phase 1 & 2 trial • 495 Patients • NCT02024607

82%

Diarrhoea

76%

Nausea

71%

Fatigue

57%

Vomiting

53%

Abdominal pain

30%

Neuropathy peripheral

27%

Dyspnoea

25%

Anaemia

23%

Neutrophil count decreased

23%

Constipation

22%

Weight decreased

21%

Hypokalaemia

20%

Oedema peripheral

18%

Dehydration

17%

Cough

17%

Neutropenia

17%

Pyrexia

17%

Peripheral sensory neuropathy

16%

Thrombocytopenia

15%

Platelet count decreased

15%

Back pain

13%

Mucosal inflammation

13%

Temperature intolerance

13%

Dysgeusia

13%

Chromaturia

12%

White blood cell count decreased

12%

Urinary tract infection

11%

Dizziness

11%

Depression

10%

Hyponatraemia

10%

Stomatitis

10%

Ascites

10%

Dysphagia

10%

Anxiety

Headache

Abdominal distension

Insomnia

Arthralgia

Asthenia

Pain in extremity

Alopecia

Urine ketone body present

Blood alkaline phosphatase increased

Pulmonary embolism

Lymphopenia

Leukopenia

Blood bilirubin increased

Dyspepsia

Sepsis

Palmar-plantar erythrodysaesthesia syndrome

Hypertension

Urine leukocyte esterase positive

Abdominal pain upper

Gastrooesophageal reflux disease

Proteinuria

Rash

Flatulence

Chills

Dry mouth

Myalgia

Epistaxis

Muscle spasms

Pneumonia

pelvic fracture

Haematemesis

Disease progression

Pleural effusion

Confusional state

Mental status changes

malignant neoplasm progression

Large intestine perforation

Oesophagitis

Lung abscess

embolism

pancreatic carcinoma

fall

Death

Haemorrhage intranial

Atrial fibrillation

Colitis

Enterocutaneous fistula

Gastrointestinal haemorrhage

Upper gastrointestinal haemorrhage

Chest pain

somnolence

syncope

Febrile neutropenia

Acute kidney injury

Acute respiratory failure

Hypoxia

Pneumonia aspiration

Clostridium difficile colitis

Influenza

Perirectal abscess

Salmonella sepsis

Septic shock

hip fracture

deep vein thrombosis

haematoma

pelvic venous thrombosis

Cholangitis

Ischaemic cerebral infarction

Hyperglycaemia

subdural haematoma

100%

80%

60%

40%

20%

Study treatment Arm

Napabucasin Plus FOLFOX6

Napabucasin Plus FOLFOX6 Plus Bevacizumab

Napabucasin Plus FOLFIRI Plus Bevacizumab

Napabucasin Plus Regorafenib

Napabucasin Plus FOLFIRI

Napabucasin Plus Irinotecan

Napabucasin Plus CAPOX

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

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: Treatment (pembrolizumab, regorafenib)Experimental Treatment2 Interventions

Participants receive pembrolizumab IV over 30 minutes on day 1 and regorafenib PO QD on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

FDA approved

Regorafenib

FDA approved

0 / 24Eligibility 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

Regorafenib and pembrolizumab are two treatments being studied for colorectal cancer. Regorafenib works by inhibiting multiple protein kinases involved in tumor growth, angiogenesis, and the tumor microenvironment, thereby slowing cancer progression. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that blocks the PD-1 receptor, enhancing the immune system's ability to recognize and destroy cancer cells. These mechanisms are important for colorectal cancer patients as they offer targeted approaches to control tumor growth and improve survival rates.

Regorafenib in the treatment of colorectal cancer.