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

Condition(s) studied

Investigational drug(s) / intervention(s)

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

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

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

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

Study 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).

Eligibility

Primary outcome measure(s)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part 1 — Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
• Number of Participants With Dose Limiting Toxicities (DLTs) in Part 1 — From Day 1 to 28 days after the first dose of novel oncology therapy (durvalumab and oleclumab)
  DLT: Any study drug related Grade (G)3 or higher toxicity including: any G3/G4 immune-mediated AE, any G3/4 noninfectious pneumonitis/colitis, transaminase elevation (TE) \>8x upper limit of normal (ULN) or total bilirubin (TBL) \>5xULN, increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>=3xULN along with TBL \>=2xULN, isolated liver TE \>5 but =\<8xULN or isolated TBL \>3 but =\<5xULN that does not downgrade to G1 or less within 14 days of onset, G3 nausea/vomiting/diarrhea that does not resolve to G2 or less within 3 days of maximal supportive care (MSC), G3/4 febrile neutropenia, G3/4 neutropenia not associated with fever/systemic infection, G4 anemia, G3 anemia with clinical sequelae/requires \>2 units of red blood cells transfusion, thrombocytopenia (G4 \>=7 days, G3 that did not improve by at least 1 grade within 7 days, G3/4 associated with G3/higher hemorrhage).
• Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 1 — Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years)
  Number of participants with at least common terminology criteria for adverse events (CTCAE v5.0) 2-grade shift from baseline (last assessment prior to first dose) to worst toxicity grade in clinical laboratory parameters are reported. Clinical laboratory parameter analysis included hematology, clinical chemistry, coagulation, and urinalysis.
• Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 1 — Day 1 through 90 days after the last dose of study drug (approximately 2.8 years)
  Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, and pulse rate).
• Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in Part 2 — Randomization through end of study (approximately 2.6 years)
  The OR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 criteria. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesion. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. In Part 2, randomization occurred between Day -8 and the same date as dosing.

Trial sites (21)

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