COLUMBIA-1: Novel Oncology Therapies in Combination With Chemotherapy and Bevacizumab as First- Line Therapy in MSS-CRC

NCT ID: NCT04068610

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-13
• Study Completion Date: 2026-11-24

Brief Summary

COLUMBIA-1 is a Phase 1b/2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) alone and in combination with novel oncology therapies in first-line metastatic microsatellite-stable colorectal cancer (MSS-CRC).

Detailed Description

COLUMBIA-1 is a Phase 1b/2, open-label, multicenter, randomized, multidrug platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) in combination with novel oncology therapies in patients with first-line metastatic MSS-CRC. The study is designed to concurrently evaluate potential novel combinations with clinical promise using a 2-part approach. Part 1 is a Phase 1b study of safety, and Part 2 is a Phase 2 study of efficacy and safety.

Conditions

Metastatic Microsatellite-stable Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab

Participants in Part 1 safety run-in arm (S1) will receive intravenous (IV) infusions of FOLFOX (5-fluorouracil \[5-FU\]: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Participants will receive IV infusion of durvalumab as stated in arm description.

Oleclumab

Intervention Type: DRUG

Participants will receive IV infusion of oleclumab as stated in arm description.

FOLFOX

Intervention Type: DRUG

Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.

Bevacizumab

Intervention Type: DRUG

Participants will receive IV infusion of bevacizumab as stated in arm description.

Part 2 (C1): FOLFOX + Bevacizumab

Participants in Part 2 control 1 arm (C1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.

Group Type: EXPERIMENTAL

FOLFOX

Intervention Type: DRUG

Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.

Bevacizumab

Intervention Type: DRUG

Participants will receive IV infusion of bevacizumab as stated in arm description.

Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab

Participants in Part 2 experimental 1 arm (E1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m\^2 over 46-48 hours \[Day 1 and 2 of every 14-day Cycle\], oxaliplatin: 85 mg/m\^2, folinic acid: 400 mg/m\^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met.

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Participants will receive IV infusion of durvalumab as stated in arm description.

Oleclumab

Intervention Type: DRUG

Participants will receive IV infusion of oleclumab as stated in arm description.

FOLFOX

Intervention Type: DRUG

Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.

Bevacizumab

Intervention Type: DRUG

Participants will receive IV infusion of bevacizumab as stated in arm description.

Interventions

Durvalumab

Participants will receive IV infusion of durvalumab as stated in arm description.

Intervention Type: DRUG

Oleclumab

Participants will receive IV infusion of oleclumab as stated in arm description.

Intervention Type: DRUG

FOLFOX

Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.

Intervention Type: DRUG

Bevacizumab

Participants will receive IV infusion of bevacizumab as stated in arm description.

Intervention Type: DRUG

Other Intervention Names

MEDI4736; MEDI9447

Eligibility Criteria

Inclusion Criteria

1. Written informed consent and any locally required authorization obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.

2. Age ≥ 18 years at the time of screening.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Participants must have histologic documentation of advanced or metastatic CRC and: (a) A documented mutation test during screening and confirmed tumor locations from disease assessment for enrollment. (b) Participants must NOT have defective deoxyribonucleic acid (DNA) mismatch repair (MSI) as documented by testing. (c) Participants must not have received any prior systemic therapy for recurrent/metastatic disease (prior adjuvant chemotherapy or radio-chemotherapy is acceptable so long as progression was not within 6 months of completing the adjuvant regimen).

5. Participants must have at least one lesion that is measurable by RECIST v1.1 (Eisenhauer et al, 2009).

6. Participants must have adequate organ function.

7. Participants with medical conditions requiring systemic anticoagulation (eg, atrial fibrillation) are eligible provided that both of the following criteria are met: - The participant has an in-range International Normalized Ratio (INR) on a stable dose of oral anticoagulant or be on a stable dose of low molecular weight heparin. - The participant has no active bleeding or pathological condition that carries a high risk of bleeding.

8. Body weight >35 kg.

9. Adequate method of contraception per protocol.

Exclusion Criteria

1. History of allogeneic organ transplantation.

2. Active or prior documented autoimmune disorders within the past 5 years.

3. History of venous thrombosis within the past 3 months.

4. Cardiovascular criteria: (a) Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months. (b) New York Heart Association (NYHA) class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension. (c) History of hypertensive crisis/hypertensive encephalopathy within the past 6 months.

5. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms.

6. No significant history of bleeding events or gastrointestinal perforation.

7. Uncontrolled intercurrent illness.

8. History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 5 years of low potential risk for recurrence. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease.

9. History of active primary immunodeficiency.

10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.

11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

12. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1 from previous anticancer therapy.

13. History of leptomeningeal disease or cord compression.

14. Untreated central nervous system (CNS) metastases.

15. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.

16. Known dihydropyrimidine dehydrogenase (DPD) deficiency.

17. Prior immunotherapy or anti-angiogenics.

18. Receipt of live attenuated vaccine within the past 30 days.

19. Major surgical procedure, open biopsy, or significant traumatic injury within the past 28 days.

20. Current or prior use of immunosuppressive medication within the past 14 days, with exceptions per protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 101 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Los Angeles, California, United States

Research Site

Sacramento, California, United States

Research Site

Ann Arbor, Michigan, United States

Research Site

Las Vegas, Nevada, United States

Research Site

New York, New York, United States

Research Site

Canton, Ohio, United States

Research Site

Providence, Rhode Island, United States

Research Site

Chattanooga, Tennessee, United States

Research Site

Nashville, Tennessee, United States

Research Site

Houston, Texas, United States

Research Site

Charlottesville, Virginia, United States

Research Site

Clayton, , Australia

Research Site

Heidelberg, , Australia

Research Site

Melbourne, , Australia

Research Site

Toronto, Ontario, Canada

Research Site

Nantes, , France

Research Site

Villejuif, , France

Research Site

Barcelona, , Spain

Research Site

Barcelona, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Countries

United States; Australia; Canada; France; Spain

References

Segal NH, Tie J, Kopetz S, Ducreux M, Chen E, Dienstmann R, Hollebecque A, Reilley MJ, Elez E, Cosaert J, Cain J, Soo-Hoo Y, Hewson N, Cooper ZA, Kumar R, Tabernero J. COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer. Br J Cancer. 2024 Oct;131(6):1005-1013. doi: 10.1038/s41416-024-02796-3. Epub 2024 Jul 25.

Reference Type: DERIVED

PMID: 39048638 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

2019-000974-44

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D910CC00001

Identifier Type: -

Identifier Source: org_study_id