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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

2 Jun 2023 → 27 Jun 2024

Decision date (initial)

2022-08-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc

External identifiers

EU CT number

2022-500177-13-00

ClinicalTrials.gov

NCT05330429

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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).
Randomized Cohort: To evaluate the efficacy of magrolimab in combination with bevacizumab and FOLFIRI in mCRC as determined by progression-free survival (PFS) by investigator assessment

Conditions and MedDRA coding

Metastatic Colorectal Cancer (mCRC)

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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).
2. 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.
3. Measurable disease (RECIST V1.1 criteria)
4. Individuals must have an eastern cooperative oncology group (ECOG) performance status of 0 or 1.
5. Life expectancy of at least 12 weeks.
6. Laboratory measurements, blood counts: adequate hemoglobin, neutrophil, and platelet counts
7. Adequate liver function
8. Adequate renal function
9. Note: Other protocol defined Inclusion criteria may apply

Exclusion criteria 21

1. 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.
2. 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.
3. Second malignancy, except treated basal cell or localized squamous skin carcinomas, or localized prostate cancer
4. Known v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E or MSI-H mutations or dMMR.
5. Uncontrolled pleural effusion.
6. Persistent Grade 2 or more gastrointestinal bleeding.
7. Individuals with prior irinotecan therapy.
8. Clinically significant coronary artery disease or myocardial infarction within 6 months prior to inclusion.
9. Peripheral neuropathy of more than Grade 2 (CTCAE Version 5.0).
10. Known dihydropyrimidine dehydrogenase deficiency.
11. History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, nongastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
12. Acute intestinal obstruction or subobstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colonic prosthesis.
13. Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
14. Note: Other protocol defined Exclusion criteria may apply.
15. Uncontrolled arterial hypertension.
16. Thromboembolic event in the 6 months before inclusion (eg, transitory ischemic stroke, stroke, subarachnoid hemorrhage) except peripheral deep vein thrombosis treated with anticoagulants.
17. 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.
18. 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.
19. History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
20. Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
21. Known inherited or acquired bleeding disorders.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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 ]
2. 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 ] • Percentage of Participants Experiencing Laboratory Abnormalities According to NCI-CTCAE Version 5.0 [ Time Frame: First dose date up to 3 years ]
3. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences International Limited

Contact name

EU Clinical Trials Support

Public contact point

Organisation

Gilead Sciences International Limited

Contact name

EU Clinical Trials Support

Third parties 9

Locations

5 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications