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

MedImmune

Status and phase: Withdrawn; Phase 2

Conditions: Microsatellite-stable Colorectal Cancer

Treatments: Drug: E2 - mFOLFOX6, durvalumab and oleclumab; Drug: E3 - mFOLFOX6, durvalumab and monalizumab; Drug: E1 - mFOLFOX and durvalumab; Drug: Standard of Care - mFOLFOX6

Study type: Interventional

Funder types: Industry

Identifiers

NCT04145193

D910CC00002

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Written informed consent and any locally required authorization obtained from the subject/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. Histologically proven Stage II or Stage III CRC

   Subjects must also meet the following criteria:

   1. Eligible for 6 months of mFOLFOX6 adjuvant chemotherapy within 8 weeks after surgery
   2. Must NOT have received prior systemic chemotherapy, immunotherapy, or radiotherapy for treatment of CRC.
   3. Must NOT have defective DNA mismatch repair (MSI) as documented by testing

5. Margin-negative (R0; defined as >1 mm clearance) surgical resection

6. Postoperative ctDNA-positive status defined by the presence of ctDNA derived from plasma; determined using a validated assay per protocol

7. Subjects must have adequate organ function

8. Body weight > 35 kg

9. Adequate method of contraception per protocol

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 4 patient groups

Control Arm (mFOLFOX6)

Active Comparator group

Description:

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).

Treatment:

Drug: Standard of Care - mFOLFOX6

Drug: E1 - mFOLFOX and durvalumab

Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Durvalumab

Experimental group

Description:

Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)

Treatment:

Drug: E1 - mFOLFOX and durvalumab

Drug: E3 - mFOLFOX6, durvalumab and monalizumab

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Oleclumab

Experimental group

Description:

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)

Treatment:

Drug: E2 - mFOLFOX6, durvalumab and oleclumab

Monalizumab

Experimental group

Description:

Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)

Treatment:

Drug: E3 - mFOLFOX6, durvalumab and monalizumab