What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as the combination of bevacizumab with FOLFIRI (5-fluorouracil, irinotecan, and leucovorin), are associated with several side effects. Bevacizumab can cause hypertension, bleeding, thromboembolic events, and gastrointestinal perforations. FOLFIRI is known to cause diarrhea, neutropenia, fatigue, nausea, and mucositis. Monoclonal antibodies like Magrolimab may also lead to infusion-related reactions, anemia, and fatigue. Patients undergoing these treatments should be closely monitored for these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for colorectal cancer, particularly focusing on immunotherapy and combination regimens. Pembrolizumab, an anti-PD-1 monoclonal antibody, has been approved for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer. Bevacizumab, an anti-VEGF monoclonal antibody, is often used in combination with chemotherapy agents such as 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI regimen). These treatments aim to enhance the immune response against cancer cells and inhibit tumor angiogenesis, similar to the investigational approach of combining Magrolimab with FOLFIRI and bevacizumab.

What other types of research exist?

Promising novel alternatives to Magrolimab for colorectal cancer patients in 2024 include: 1) Pembrolizumab (anti-PD-1 therapy) in combination with other agents like lenvatinib, 2) Nivolumab (anti-PD-1 therapy) combined with ipilimumab (anti-CTLA-4 therapy), 3) Encorafenib (BRAF inhibitor) combined with cetuximab (EGFR inhibitor) for BRAF V600E-mutant colorectal cancer, and 4) Trastuzumab deruxtecan (HER2-targeted antibody-drug conjugate) for HER2-positive colorectal cancer. These therapies have shown promising results in clinical trials and may offer effective treatment options for patients.

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Monoclonal Antibodies

Magrolimab + FOLFIRI/BEV for Colorectal Cancer (ELEVATE CRC Trial)

Phase 2

Waitlist Available

Research Sponsored by Gilead Sciences

Eligibility Criteria Checklist

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

Must have

Previously treated individuals with inoperable metastatic colorectal cancer (mCRC) who are ineligible for checkpoint inhibitor therapy (microsatellite instability (MSI)-H or mismatch repair deficient (dMMR) and are excluded)

Individuals must have an eastern cooperative oncology group (ECOG) performance status of 0 or 1

Must not have

Individuals with prior irinotecan therapy

Peripheral neuropathy of more than Grade 2 (CTCAE Version 5.0)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

Summary

This trial is testing a new treatment combining magrolimab, bevacizumab, and a chemotherapy mix for patients with advanced colorectal cancer that hasn't responded to other treatments. The goal is to see if this combination is safe and effective. Magrolimab helps the immune system attack cancer, bevacizumab cuts off the tumor's blood supply, and the chemotherapy mix kills cancer cells.

Who is the study for?

This trial is for adults with advanced inoperable metastatic colorectal cancer who've had one prior treatment excluding those with certain genetic mutations or conditions. Participants must have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory, and meet specific blood count and organ function criteria.

What is being tested?

The study tests the safety and effectiveness of Magrolimab combined with FOLFIRI/BEV (a chemotherapy regimen) in patients who have previously treated mCRC. It aims to determine the best dose for Phase 2 trials and how well this combination works against the cancer.

What are the potential side effects?

Potential side effects may include immune-related reactions, infusion-related symptoms, fatigue, gastrointestinal issues like diarrhea or nausea, low blood counts increasing infection risk, liver function changes, and possibly hypertension due to Bevacizumab.

Eligibility Criteria

Inclusion Criteria

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

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I have colorectal cancer that cannot be removed by surgery and I can't receive certain immune therapies.

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I am fully active or can carry out light work.

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 irinotecan.

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I do not have severe numbness or pain in my hands or feet.

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I have a known bleeding disorder.

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I needed more than 2 blood transfusions in the last month.

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I have fluid buildup in my chest that isn't managed.

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I have an unhealed wound, stomach ulcer, or broken bone.

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I haven't had hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.

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I have ongoing serious GI bleeding.

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I have a history of serious gut issues or have a device in my colon.

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My high blood pressure is not under control.

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I have a known deficiency in the enzyme dihydropyrimidine dehydrogenase.

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My cancer has a specific BRAF mutation or is MSI-H/dMMR.

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I haven't had cancer treatment within the last 3 weeks or 4 half-lives before starting magrolimab.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0

Safety Run-in Cohort: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

+1 more

Secondary outcome measures

Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score

Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score

Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1

+5 more

Side effects data

From 2020 Phase 1 & 2 trial • 78 Patients • NCT02953782

50%

Dry skin

40%

Pyrexia

40%

Headache

35%

Diarrhoea

35%

Fatigue

35%

Infusion related reaction

30%

Constipation

30%

Stomatitis

30%

Dermatitis acneiform

25%

Chills

25%

Decreased appetite

25%

Rash maculo-papular

25%

Hypomagnesaemia

25%

Blood bilirubin increased

20%

Anaemia

20%

Vomiting

20%

Hypokalaemia

20%

Depression

20%

Cough

15%

Dyspnoea

15%

Nausea

15%

Dehydration

15%

Lymphocyte count decreased

15%

Insomnia

10%

Arthralgia

10%

Oedema peripheral

10%

Rhinitis allergic

10%

Pruritus

10%

Rash

10%

Hypertension

10%

Abdominal pain

10%

Dizziness

10%

Tumour pain

10%

Haematuria

Small intestinal obstruction

Iron deficiency anaemia

Malignant neoplasm progression

Lung infection

Tooth abscess

Vaginal infection

White blood cell count decreased

Dysgeusia

Interstitial lung disease

Flushing

Raynaud's phenomenon

Respiratory failure

Musculoskeletal chest pain

Pollakiuria

Pulmonary congestion

Restless legs syndrome

Syncope

Tremor

Strabismus

Blepharal pigmentation

Abdominal distension

Enterocolitis

Gastrooesophageal reflux disease

Glossodynia

Chest discomfort

Influenza like illness

Non-cardiac chest pain

Blood sodium decreased

Weight decreased

Hypophosphataemia

Laryngeal haemorrhage

Pulmonary haemorrhage

Urinary hesitation

Immune thrombocytopenic purpura

Haemoptysis

Loose tooth

Early satiety

Pharyngitis

Fall

Alanine aminotransferase increased

Urticaria

Hypotension

Jugular vein thrombosis

Lymph node pain

Oedema

Bronchitis

Conjunctivitis

Upper respiratory tract infection

Pelvic fracture

Dysaesthesia

Epistaxis

Acne

Aspartate aminotransferase increased

Blood alkaline phosphatase increased

Platelet count decreased

Back pain

Flank pain

Musculoskeletal pain

Myalgia

Cerebral infarction

Restlessness

100%

80%

60%

40%

20%

Study treatment Arm

Magrolimab 45 mg/kg

Magrolimab Priming Dose Only

Magrolimab 10 mg/kg

Magrolimab 20 mg/kg

Magrolimab 30 mg/kg

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRIExperimental Treatment5 Interventions

Participants will receive magrolimab in de-escalating doses to establish recommended Phase 2 dose (RP2D) in combination with + bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).

Group II: Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRIExperimental Treatment5 Interventions

Participants will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).

Group III: Randomized Cohort: Bevacizumab + FOLFIRIActive Control4 Interventions

Participants will receive bevacizumab (5 mg/kg every 2 weeks) + FOLFIRI (irinotecan 180 mg/m^2 + leucovorin 400 mg/m^2 + fluorouracil 400 mg/m^2 bolus followed by 2400 mg/m^2 continuous on Days 1, 2, 15, and 16 of a 28-Day Cycle).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fluorouracil

2014

Completed Phase 3

~11700

Magrolimab

2021

Completed Phase 2

~210

Irinotecan

2017

Completed Phase 4

~2680

Leucovorin

2005

Completed Phase 4

~6010

Bevacizumab

2013

Completed Phase 4

~5280

0 / 15Eligibility 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

Common treatments for colorectal cancer include chemotherapy agents like 5-fluorouracil (5-FU) and oxaliplatin, which work by interfering with DNA synthesis and repair, leading to cancer cell death. Targeted therapies such as bevacizumab inhibit angiogenesis, the process by which tumors develop new blood vessels, thereby starving the tumor of nutrients. Immunotherapies, including checkpoint inhibitors like pembrolizumab, enhance the immune system's ability to recognize and destroy cancer cells. Magrolimab, an anti-CD47 monoclonal antibody, works by blocking the 'don't eat me' signal on cancer cells, allowing the immune system to target and eliminate them. This is particularly important for colorectal cancer patients as it offers a novel mechanism to potentially overcome resistance to traditional therapies and improve treatment outcomes.