Novel Oncology Therapies in Combination With Adjuvant Chemo in High-risk MSS-CRC

Phase 2

Withdrawn

• Conditions: Microsatellite-stable Colorectal Cancer
• Interventions: Drug: Standard of Care - mFOLFOX6; Drug: E1 - mFOLFOX and durvalumab; Drug: E2 - mFOLFOX6, durvalumab and oleclumab; Drug: E3 - mFOLFOX6, durvalumab and monalizumab

• Registration Number: NCT04145193
• Lead Sponsor: MedImmune LLC

Brief Summary

Columbia 2 is a Phase 2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX) alone and in combination with novel oncology therapies in adjuvant high-risk microsatellite-stable colorectal cancer

Detailed Description

Columbia 2 is a Phase 2, open-label, randomized, multicenter, platform study of novel oncology therapies in combination with adjuvant chemotherapy in patients with high-risk microsatellite-stable colorectal cancer.

Study Timeline

• Study First Submitted: 2019-10-16
• Study First Submitted QC: 2019-10-29
• Study First Posted: 2019-10-30
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-17
• Last Update Posted: 2020-09-21
• Study Start: 2020-10-01
• Primary Completion: 2024-03-19
• Study Completion: 2024-03-19

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

1. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

2. Evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc").

3. History of allogeneic organ transplantation.

4. Active or prior documented autoimmune disorders within the past 5 years as noted in the protocol.

5. Cardiac and vascular criteria:

   1. History of venous thrombosis within the past 3 months prior to the scheduled first dose of study treatment.
   2. 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 prior to the scheduled first dose of study treatment.
   3. New York Heart Association (NYHA) Class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension.
   4. History of hypertensive crisis/hypertensive encephalopathy within the past 6 months prior to the scheduled first dose of study treatment.
   5. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms

6. Uncontrolled intercurrent illness, see the protocol for details.

7. History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 5 years prior to the scheduled first dose of study treatment and of low potential risk for recurrence

8. History of active primary immunodeficiency.

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

10. Known allergy or hypersensitivity to any of the investigational product or noninvestigational product formulations.

11. Any condition that, in the opinion of the investigator, would prevent the initiation of 6 months adjuvant therapy within 8 weeks of surgery

12. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.

13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the scheduled first dose of study treatment, or anticipation of the need for major surgical procedure during the course of the study.

14. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Control Arm (mFOLFOX6)	Standard of Care - mFOLFOX6	Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Control Arm (mFOLFOX6)	E1 - mFOLFOX and durvalumab	Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Control Arm (mFOLFOX6)	E2 - mFOLFOX6, durvalumab and oleclumab	Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Control Arm (mFOLFOX6)	E3 - mFOLFOX6, durvalumab and monalizumab	Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
Durvalumab	E1 - mFOLFOX and durvalumab	Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
Durvalumab	E2 - mFOLFOX6, durvalumab and oleclumab	Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
Durvalumab	E3 - mFOLFOX6, durvalumab and monalizumab	Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
Oleclumab	E2 - mFOLFOX6, durvalumab and oleclumab	Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)
Monalizumab	E3 - mFOLFOX6, durvalumab and monalizumab	Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)

Primary Outcome Measures

Name	Time	Method
ctDNA clearance	From the time of first dose to 6 months post treatment	ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months)

Secondary Outcome Measures

Name	Time	Method
Incidence of adverse events	From time of first dose to 90 days post last dose	The secondary endpoint of safety as assessed by the number of subjects with adverse events and serious adverse events
Disease free survival	From time of first dose till end of study (5 years)	From randomization until time of first documented incidence of disease recurrence, secondary cancer, or death due to any cause, whichever occurs first
Disease free survival at 12 months	From time of first dose till end of study (5 years)	Percentage of subject who are disease free at 12 months post first dose of treatment
overall survival	From time of first dose till end of study (5 years)	From randomization until death due to any cause
Serum conenctration levels of novel agents in combination with mFOLFOX6	From Day 1 up to 90 days post last dose	Pharmacokinetics of novel agents in combination with FOLFOX
Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6	From Day 1 up to 90 days post last dose	Immunogenicity of novel agents in combination with mFOLFOX6