CAB-ROR2-ADC Safety and Efficacy Study in Patients With TNBC or Head & Neck Cancer (Ph1) and NSCLC or Melanoma (Ph2)

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-ROR2-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 BA3021, a conditionally active biologic (CAB) ROR2-targeted antibody drug conjugate (CAB-ROR2-ADC) BA3021 in patients with advanced solid tumors. This study will consist of a dose escalation phase and a dose expansion phase with BA3021 in Phase 1. Phase 2 will study BA3021 alone or in combination with a PD-1 inhibitor.

Official Title
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A Phase 1/2 Safety and Efficacy Dose Escalation / Dose Expansion Study of a CAB-ROR2-ADC, Alone and in Combination With a PD-1 Inhibitor, in Patients With Advanced Solid Tumors (Ph1) and Melanoma and NSCLC Patients (Ph2)

Conditions
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Non Small Cell Lung Cancer, Triple Negative Breast Cancer, Melanoma, Head and Neck Cancer

Intervention / Treatment
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* Biological: CAB-ROR2-ADC
* Biological: PD-1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor and have failed all available standard of care (SoC) therapy and for whom no curative therapy is available or who are not eligible, intolerant to or refuse standard therapy. Patients must have measurable disease. For the dose expansion phase: Patients with locally advanced unresectable or metastatic, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC) and soft tissue sarcoma (STS) Age ≥ 18 years. 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 BA3021 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: 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy - CAB-ROR2-ADC (BA3021) alone<br>BA3021 alone Q2W dosing regimen | Biological: CAB-ROR2-ADC<br>* Conditionally active biologic anti-ROR2 antibody drug conjugate<br>* Other names: BA3021;|
| Experimental: Combination Therapy<br>CAB-ROR2-ADC (BA3021) with PD-1 inhibitor | Biological: CAB-ROR2-ADC<br>* Conditionally active biologic anti-ROR2 antibody drug conjugate<br>* Other names: BA3021;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 Objective Response Rate (ORR) | Proportion of patients who achieve a confirmed CR or PR | 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 | Up to 24 months | 
| Phase 1: Confirmed Objective 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 BA3021 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 |