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

MedImmune

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Microsatellite-stable Colorectal Cancer

Treatments: Drug: FOLFOX; Drug: Bevacizumab; Drug: Durvalumab; Drug: Oleclumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04068610

D910CC00001

2019-000974-44 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Oleclumab

Drug: Durvalumab

Drug: Bevacizumab

Drug: FOLFOX

Part 2 (C1): FOLFOX + Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Bevacizumab

Drug: FOLFOX

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

Experimental group

Description:

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.

Treatment:

Drug: Oleclumab

Drug: Durvalumab

Drug: Bevacizumab

Drug: FOLFOX