CAB-AXL-ADC Safety and Efficacy Study in Adult and Adolescent Patients With Sarcoma

Study Overview
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Brief Summary
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The objective of this study is to assess safety and efficacy of CAB-AXL-ADC in solid tumors

Detailed Description
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This is a multi-center, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of BA3011, a conditionally active biologic (CAB) AXL-targeted antibody drug conjugate (CAB-AXL-ADC) in patients with advanced solid tumors in Phase 1 and BA3011 alone and in combination with a PD-1 inhibitor in Phase 2. Phase 1 of this study will consist of a dose escalation phase (enrollment complete as of Oct 2019) and a dose expansion phase (still enrolling ACC patients only). Phase 2 is targeted to begin in Q3 2020 and will include both adult and adolescents age 12 and over.

Official Title
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A Phase 1/2 Dose Escalation and Dose Expansion Study of Mecbotamab Vedotin (BA3011) Alone and in Combination With Nivolumab in Adult and Adolescent Patients 12 Years and Older With Advanced Solid Tumors

Conditions
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Undifferentiated Pleomorphic Sarcoma, Liposarcoma, Synovial Sarcoma, Osteosarcoma, Ewing Sarcoma

Intervention / Treatment
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* Biological: CAB-AXL-ADC
* Biological: PD-1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have measurable disease. Age ≥ 12 years (Phase 2) Adequate renal function Adequate liver function Adequate hematological function Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least three months. Exclusion Criteria: Patients must not have clinically significant cardiac disease. Patients must not have known non-controlled CNS metastasis. Patients must not have a history of ≥ Grade 3 allergic reactions to mAb therapy as wellas known or suspected allergy or intolerance to any agent given during this study. Patients must not have had major surgery within 4 weeks before first BA3011 administration. Patients must not have had prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload. Patients must not have known human immunodeficiency virus (HIV) infection, active hepatitis B and/or hepatitis C. Patients must not be women who are pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 12 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BA3011<br>Phase 1: All patients will receive BA3011, CAB-AXL-ADC. Phase 2: All patients will receive either BA3011 alone or in combination with PD-1 inhibitor. | Biological: CAB-AXL-ADC<br>* Conditionally active biologic anti-AXL antibody drug conjugate<br>|
| Experimental: Combination Therapy<br>Phase 2: BA3011 in combination with PD-1 inhibitor. | Biological: CAB-AXL-ADC<br>* Conditionally active biologic anti-AXL antibody drug conjugate<br>Biological: PD-1 inhibitor<br>* PD-1 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Safety Profile | Assess dose limiting toxicity as defined in the protocol | Up to 24 months | 
| Phase 1: Safety Profile | Assess maximum tolerated dose as defined in the protocol | Up to 24 months | 
| Phase 1 and 2: Safety Profile | Frequency and severity of AEs and/or SAEs | Up to 24 months | 
| Phase 2: Confirmed overall response rate (ORR) per RECIST v1.1 | Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Pharmacokinetics | Plasma concentrations of ADC, total antibody and MMAE | Up to 24 months | 
| Phase 1: Pharmacokinetics | Peak Plasma Concentration (Cmax) | Up to 24 months | 
| Phase 1: Pharmacokinetics | Area under the plasma concentration versus time curve (AUC) | Up to 24 months | 
| Phase 1: Overall response rate (ORR) | Proportion of patients who achieve a confirmed CR or PR | Up to 24 months | 
| Phase 1: Immunogenicity | The number and percentage of patients who develop detectable anti-drug antibodies (ADAs) | Up to 24 months | 
| Phase 1 and 2: Duration of response (DOR) | Time from the first documented OR until the first documented disease progression or death (due to any cause), whichever occurs first | Up to 24 months | 
| Phase 1 and 2: Progression-free survival (PFS) | Time from the first dose of IP until the first documentation of disease progression or death due to any cause, whichever occurs first | Up to 24 months | 
| Phase 1 and 2: Best overall response (OR) | All post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy | Up to 24 months | 
| Phase 1 and 2: Disease control rate (DCR) | Proportion of patients with a best overall response of confirmed CR, confirmed PR, or stable disease (SD) ≥ 12 weeks | Up to 24 months | 
| Phase 1 and 2: Time to response (TTR) | Time from the first dose of investigational product until the first documentation of OR | Up to 24 months | 
| Phase 1 and 2: Overall survival (OS) | Time from the first dose of BA3011 treatment until death due to any cause | Up to 24 months | 
| Phase 1 and 2: Tumor size | Percent change from baseline in tumor size | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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late stage, stage 3, stage 4, cancer