A Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This study is designed as an open-label, adaptive Simon Two-Stage study to evaluate the efficacy of CTX-009 in patients with metastatic colorectal cancer. A Simon Two-Stage adaptive design will enroll approximately 37 patients into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled.

Official Title
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A Phase 2 Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer Who Have Received Two or Three Prior Systemic Chemotherapy Regimens

Conditions
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Metastatic Colorectal Cancer, Colon Cancer, Rectal Cancer

Intervention / Treatment
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* Drug: CTX-009


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Histologically or cytologically confirmed metastatic or recurrent colorectal cancers The primary tumor must have been resected > 3 months prior to planned C1D1. Patients who experienced progressive disease or relapse after receiving two or three prior lines of systemic therapy in the locally advanced or metastatic setting. Prior lines of systemic treatment must have included at least one fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab containing chemotherapy regimen (in any combination and may have been administered in the neoadjuvant setting). Patients whose tumor is not right sided and RAS wild type must also have received an anti-epidermal growth factor receptor (EGFR) therapy. Patients with tumors harboring mutations or other alterations for which there are available targeted therapies (e.g. BRAF V600E, HER2-positive, MSI-H/dMMR, etc.) must have also received the relevant approved targeted therapies. If patient received peri-operative treatment (neoadjuvant and/or adjuvant), please consult the Sponsor Medical Monitor for review of prior treatment lines. At least one lesion measurable as defined by RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Predicted life expectancy of at least 12 weeks Adequate hepatic and renal function within 14 days of C1D1 as described below: Total bilirubin ≤ 1.5 X upper limit of normal (ULN) Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 3.0 X ULN (≤ 5x ULN in case of hepatic metastasis) Estimated creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault estimated creatinine clearance Urine protein ≤ 1+ by spot urinalysis (or, if > 1+ then 24 hr urine protein <1.0 g/24 hr) Female patients who are women of childbearing potential (WCBP) must have a negative pregnancy test (serum-human chorionic gonadotropin [hCG] or urine-hCG) at Screening within 14 days of C1D1 Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commit to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before any protocol-directed screening procedures are performed Exclusion Criteria: From the time point of signed informed consent, Less than 4 weeks have elapsed since patients had a surgery or major procedure Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy Prior to planned C1D1, Less than 4 weeks have elapsed since patients had chemotherapy or targeted therapy for colorectal cancer Less than 4 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment A history of the following cardiovascular diseases in past 5 years may be exclusionary, as determined by the Sponsor Medical Monitor: Congestive heart failure that corresponds to Class II or a higher class under New York Heart Association (NYHA) classification or less than 50% of left ventricular ejection fraction (LVEF) Uncontrolled hypertension (systolic blood pressure [SBP]/diastolic blood pressure [DBP] > 140/90 mmHg) (e.g., patient with SBP/DBP > 140/90 mmHg despite the best care including anti-hypertensive medications) Patients with a history of hypertensive crisis or pre-existing hypertensive encephalopathy Pulmonary hypertension Myocardial infarction Uncontrolled arrhythmia Unstable angina Patients with any significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to the initial treatment of the investigational product Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis can participate provided that systemic corticosteroid treatment was discontinued at least 4 weeks prior to screening and that the patient is radiologically and neurologically stable or improving) A history of the following hemorrhage-related or gastroenterological disease: Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor invasion into great arteries History of clinically significant and active (within 6 months) gastroenterological disease, such as peptic ulcer, gastrointestinal (GI) bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease. Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant drugs (warfarin, heparin, direct thrombin inhibitors, etc.) within 2 weeks prior to C1D1, or are expected to need those drugs during the clinical study. Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted): NSAIDs: Up to 3 consecutive days' use is permitted Corticosteroids: Topical use of corticosteroid, such as topical intra-articular injection, intranasal administration, eye drops, inhaler, etc., or temporary systemic corticosteroid use for treatment and prevention of patient's contrast media allergy, or adverse event, is permitted Severe infection requiring systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Inactive hepatitis B carriers who tested HBsAg positive may enroll provided that the patient's liver function values are normal. Also, patients with chronic HBV infection which has been controlled by the site's treatment guideline may enroll. HCV patients showing sustained viral response or patients with immunity to HBV infection may enroll Patients with other severe diseases or uncontrolled illnesses that warrant the exclusion from the study (permitted only if medically controlled) including but not limited to: Pre-existing hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to screening Major, unhealed injury, active ulcer or untreated fracture History of cerebrovascular incident (ischemic or hemorrhagic stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months prior to screening Moderate to severe ascites and/or pleural effusion Clinically significant abnormal electrocardiography (ECG) findings or history determined as clinically significant by the Investigator QT interval (Fridericia's formula) (QTcF) interval > 450 msec at the time of screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Approximately 37 patients will be enrolled into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled, for a total of approximately 84 patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTX-009 Treatment<br> | Drug: CTX-009<br>* IV infusion administered on day 1 and 15 of every 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Percentage of patients whose Best Overall Response (BOR) is assessed as Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1 | From Cycle 1 Day 1 (C1D1) to treatment discontinuation for any reason, average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Percentage of patients whose BOR is assessed as CR, PR, or Stable Disease (SD) | From C1D1 to treatment discontinuation for any reason, average of 6 months | 
| Duration of Response | The time between the date of the radiological evaluation that first confirmed CR or PR and the date of the radiation evaluation that first confirmed Progressive Disease (PD) | From first confirmed CR or PR to confirmed PD, average of 6 months | 
| Progression Free Survival | Time from C1D1 until the date of objective PD (as assessed by RECIST v1.1) or the date of death (by any cause in the absence of disease progression) | From C1D1 to first documented objective PD or death if PD does not occur, average of 6 months | 
| Overall Survival | Time from C1D1 until the date of death by any cause. Patients who are still alive at the time of the analysis, or who have become lost to follow-up or withdrawn consent will be censored at their last date known to be alive | From C1D1 to death from any cause, average of 9 months | 
| Safety Profile of CTX-009 | Incidence of Treatment Emergent Adverse Events (TEAEs) and changes in clinical abnormalities for all randomized patients who received at least one dose of study treatment | From C1D1 to 60 days after the last dose of study treatment, average of 7 months | 
| Quality of Life Changes | Assessed approximately every 2 months from patient reported data using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 as compared to baseline responses | From screening to treatment discontinuation for any reason, average of 6 months | 
| Exposure Response by Pharmacokinetic (PK) Sampling | Serum concentrations of CTX-009 at specified timepoints | From C1D1 to treatment discontinuation for any reason, average of 6 months |