A Study of CTX-009 (ABL001) in Combination With Irinotecan or Paclitaxel in Advanced or Metastatic Solid Tumor Patients

Study Overview
=================
Brief Summary
-----------------
This study is a Phase 1b/2 multi-center study to assess the safety, tolerability, pharmacokinetics of CTX-009 (ABL001) in combination with Irinotecan or Paclitaxel in patients with advanced or metastatic solid tumors.

Detailed Description
-----------------
Phase 1b Study: Indication of phase 1b study is the advanced or metastatic solid tumors (including, but not limited to, colorectal cancer, gastric cancer, and ovarian cancer). Phase 2 Study: Indication of phase 2 study is unresectable advanced, metastatic or recurrent biliary tract cancer (BTC) (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma).

Official Title
-----------------
A Phase 1b/2a Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics of CTX-009 (ABL001) in Combination With Irinotecan or Paclitaxel in Patients With Advanced or Metastatic Solid Tumors

Conditions
-----------------
P1b: Advanced Solid Tumors, P2: Biliary Tract Cancer

Intervention / Treatment
-----------------
* Drug: CTX-009 (ABL001)
* Drug: Paclitaxel
* Drug: Irinotecan


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: P1b only: Patients with histologically or cytologically confirmed metastatic or unresectable advanced solid tumors P2 only: Patients with histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, ampullary carcinoma) P2 only: Patients who have shown disease progress or recurrence of disease after receiving first-line or second-line systemic chemotherapy, including treatment with gemcitabine in combination with a platinum agent Patients aged 19 years or older At least one lesion measurable defined by response evaluation criteria in solid tumors (RECIST) version 1.1. Life expectancy ≥ 12 weeks ECOG performance status 0 or 1 Women of childbearing potential must have a negative pregnancy test outcome Patients must provide written informed consent to voluntary participation in this study Key Exclusion Criteria: History of hypersensitivity reactions to any of the components of the investigational product or other drugs of the same class (humanized/human monoclonal antibody) and irinotecan or paclitaxel Less than 4 weeks have elapsed since a surgery History of cardiac illness: New York Heart Association (NYHA) class ≥ II congestive heart failure (CHF), uncontrolled hypertension, hypertension crisis, pulmonary hypertension, myocardial infarction, uncontrolled arrhythmia, unstable angina Persistent, clinically significant NCI-CTCAE v5.0 Grade ≥ 2 toxicities from the previous anticancer therapy Severe infections or major and unhealed injury (active ulcer, untreated fracture) Symptomatic or uncontrolled central nervous system (CNS) metastasis Pregnant or lactating women or patients planning to become pregnant during the study Participation in another clinical trial within 30 days prior to initiation of study treatment and received an investigational drug treatment Administration of antiplatelets or anticoagulants within 2 weeks prior to screening Requiring continuous treatment with systemic NSAIDs or systemic corticosteroids HIV or other severe diseases that warrant the exclusion from this study

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTX-009 (ABL001) and Paclitaxel (P1b)<br> | Drug: CTX-009 (ABL001)<br>* CTX-009 (ABL001) will be administered biweekly.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered weekly.<br>|
| Experimental: CTX-009 (ABL001) and Irinotecan (P1b)<br>1 cycle = 4weeks | Drug: CTX-009 (ABL001)<br>* CTX-009 (ABL001) will be administered biweekly.<br>Drug: Irinotecan<br>* Irinotecan will be administered biweekly.<br>|
| Experimental: CTX-009 (ABL001) and Paclitaxel (P2)<br>1 cycle = 4weeks | Drug: CTX-009 (ABL001)<br>* CTX-009 (ABL001) will be administered biweekly.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered weekly.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P1b: Proportion of subjects with Dose-Limiting Toxicity (DLT) | Number of subjects who experience DLT events during 28 days after first administration of CTX-009 (ABL001) and Irinotecan/Paclitaxel, divided by the number of DLT-evaluable subjects | From Day 1 until disease progression or Day 28, whichever came first | 
| P2: Objective response rate (ORR) of CTX-009 (ABL001) in combination with paclitaxel in patients with BTC | The proportion of subjects whose best overall response (BOR) is assessed to be complete response (CR) or partial response (PR) as per Independent Radiology Center's review | Up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Severity of AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Up to approximately 24 months | 
| Pharmacokinetics (PK) of CTX-009 (ABL001) | Serum concentrations of CTX-009 (ABL001) will be collected and analyzed to evaluate the PK of CTX-009 (ABL001) | Up to approximately 24 months | 
| Objective response rate (ORR) | Proportion of subject with best overall response of complete response (CR) or partial response (PR) as per investigator's review | Up to approximately 24 months | 
| Disease control rate (DCR) | Proportion of subjects with a best overall response of complete response (CR), partial response (PR) or stable disease (SD) | Up to approximately 24 months | 
| Time to treatment failure (TTF) | Time interval from 1st administration of CTX-009 (ABL001) to the time of disease progression or discontinuation of CTX-009 (ABL001) due to whatever reason, whichever comes first | Up to approximately 24 months | 
| Duration of response (DOR) | Time interval from first occurrence of a documented objective response to the time of disease progression | Up to approximately 24 months | 
| Progression-free survival (PFS) | The time from the initiation of treatment to the first radiologic assessment that confirms progression of tumor or to death | Up to approximately 24 months | 
| P2: Survival rate | The proportion of subjects who have survived at 6 months and 12 months from the initiation of treatment | 6 months and 12 months | 
| P2: Overall survival (OS) | Time from the initiation of treatment to death | Up to approximately 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VEGF, DLL4, Solid Tumors, Bispecific antibody, anti-angiogenic