Study of Magrolimab Given Together With FOLFIRI/BEV in Patients With Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC) (ELEVATE CRC)
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| ClinicalTrials.gov Identifier: NCT05330429 |
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Recruitment Status :
Active, not recruiting
First Posted : April 15, 2022
Last Update Posted : April 26, 2024
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Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
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Brief Summary:
The goals of this clinical study are to learn more about the safety, tolerability and effectiveness of magrolimab in combination with bevacizumab and 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI) in previously treated participants with advanced inoperable metastatic colorectal cancer (mCRC).
The primary objectives of this study are: (safety run-in cohort) to evaluate safety and tolerability, and the recommended Phase 2 dose (RP2D) and (randomized cohort) to evaluate the efficacy of magrolimab in combination with bevacizumab and 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI) in previously treated participants with advanced inoperable metastatic colorectal cancer (mCRC).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Colorectal Cancer | Drug: Magrolimab Drug: Bevacizumab Drug: Irinotecan Drug: Fluorouracil Drug: Leucovorin | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 135 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Bevacizumab and FOLFIRI Versus Bevacizumab and FOLFIRI in Previously Treated Advanced Inoperable Metastatic Colorectal Cancer (mCRC) |
| Actual Study Start Date : | July 8, 2022 |
| Estimated Primary Completion Date : | March 2025 |
| Estimated Study Completion Date : | November 2026 |
Resource links provided by the National Library of Medicine
Drug Information
available for:
Bevacizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Safety Run-in Cohort: Magrolimab + Bevacizumab + FOLFIRI
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).
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Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Bevacizumab Administered intravenously Drug: Irinotecan Administered intravenously
Other Name: CAMPTOSAR® Drug: Fluorouracil Administered intravenously Drug: Leucovorin Administered intravenously |
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Experimental: Randomized Cohort: Magrolimab + Bevacizumab + FOLFIRI
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).
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Drug: Magrolimab
Administered intravenously
Other Name: GS-4721 Drug: Bevacizumab Administered intravenously Drug: Irinotecan Administered intravenously
Other Name: CAMPTOSAR® Drug: Fluorouracil Administered intravenously Drug: Leucovorin Administered intravenously |
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Active Comparator: Randomized Cohort: Bevacizumab + FOLFIRI
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).
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Drug: Bevacizumab
Administered intravenously Drug: Irinotecan Administered intravenously
Other Name: CAMPTOSAR® Drug: Fluorouracil Administered intravenously Drug: Leucovorin Administered intravenously |
Primary Outcome Measures :
- 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 [ Time Frame: First dose date up to 28 days ]
- Safety Run-in Cohort: Percentage of Participants Experiencing Adverse Events (AEs) According to the NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ]
- Safety Run-in Cohort: Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ]
- Randomized Cohort: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to 3 years ]PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, or death from any cause, whichever occurs first.
Secondary Outcome Measures :
- Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment Using RECIST Version 1.1 [ Time Frame: Up to 3 years ]Confirmed ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) on 2 consecutive assessments, at least 28 days apart.
- Randomized Cohort: Duration of Response (DOR) as Assessed by Investigator Assessment Per RECIST Version 1.1 [ Time Frame: Up to 3 years ]DOR is defined as time from first documentation of CR or PR to the earliest date of documented disease progression, or death from any cause, whichever occurs first.
- Randomized Cohort: Overall Survival (OS) [ Time Frame: Up to 3 years ]OS is defined as time from date of randomization to death from any cause.
- Randomized Cohort: Change From Baseline of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire EORTC-QLQ-C30 Score [ Time Frame: Baseline, up to 3 years ]The EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer patients, it is composed of 30 questions (items) resulting in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single items. Scoring of the QLQ-C30 is performed according to QLQ-C30 Scoring manual. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the participant), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the participant).
- Randomized Cohort: Change From Baseline of the 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) Score [ Time Frame: Baseline, up to 3 years ]EQ-5D-5L is an instrument for use as a measure of health outcome.The EQ-5D-5L consists of 2 sections: the EuroQoL (5 dimensions) (EQ-5D) descriptive system and the EuroQoL visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ-VAS indicate better health.
- Randomized Cohort: the Change From Baseline of the Functional Assessment of Cancer Therapy (FACT) Colorectal Symptom Index (FCSI) Score [ Time Frame: Baseline, up to 3 years ]
The FCSI is a set of brief, clinically relevant, colorectal cancer symptoms for assessing symptomatic response. It comprises the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life.
The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from "0" to "4" representing "Not at All" through to "Very Much True". The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state.
- Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time [ Time Frame: Up to end of treatment (approximately 3 years) ]
- Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab [ Time Frame: Up to end of treatment (approximately 3 years) ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- 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).
- Histologically or cytologically confirmed adenocarcinoma originating in the colon or rectum (excluding appendiceal and anal canal cancers) who have progressed on or after 1 prior systemic therapy in the setting where curative resection is not indicated. This therapy must have included chemotherapy based on 5-FU or capecitabine with oxaliplatin and either bevacizumab, or for patients with RAS wild-type and left-sided tumors, bevacizumab, cetuximab, or panitumumab.
- Measurable disease (RECIST V1.1 criteria).
- Individuals must have an eastern cooperative oncology group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Laboratory measurements, blood counts: adequate hemoglobin, neutrophil, and platelet counts
- Adequate liver function.
- Adequate renal function.
Key Exclusion Criteria:
- Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 3 weeks or within at least 4 half-lives prior to magrolimab dosing (up to a maximum of 4 weeks), whichever is shorter.
- Known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E or MSI-H mutations or dMMR.
- Persistent Grade 2 or more gastrointestinal bleeding.
- Individuals with prior irinotecan therapy.
- Clinically significant coronary artery disease or myocardial infarction within 6 months prior to inclusion.
- Peripheral neuropathy of more than Grade 2 (CTCAE Version 5.0).
- Known dihydropyrimidine dehydrogenase deficiency.
- Acute intestinal obstruction or subobstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colonic prosthesis.
- Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
- History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, nongastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
- Uncontrolled arterial hypertension.
- Thromboembolic event in the 6 months before inclusion (eg, transitory ischemic stroke, stroke, subarachnoid hemorrhage) except peripheral deep vein thrombosis treated with anticoagulants.
- Active central nervous system (CNS) disease. Individuals with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.
- Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening.
- History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
- Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
- Known inherited or acquired bleeding disorders.
- Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study.
- Second malignancy, except treated basal cell or localized squamous skin carcinomas, or localized prostate cancer.
- Uncontrolled pleural effusion.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05330429
Locations
Show 51 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
| Study Director: | Gilead Study Director | Gilead Sciences |
Additional Information:
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT05330429 |
| Other Study ID Numbers: |
GS-US-587-6156 2022-500177-13 ( Other Identifier: European Medicines Agency ) |
| First Posted: | April 15, 2022 Key Record Dates |
| Last Update Posted: | April 26, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Leucovorin Bevacizumab Magrolimab Fluorouracil |
Irinotecan Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Topoisomerase I Inhibitors Topoisomerase Inhibitors |