NBE-002 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This first-in-human study will evaluate the recommended dose for further clinical development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of NBE-002, a novel anti-ROR1 antibody-drug conjugate, in patients with advanced solid tumors.

Official Title
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A First-in-Human, Phase 1/2 Study of NBE-002, an Anti-ROR1 Antibody Drug Conjugate, in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor, Advanced Cancer, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: NBE-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age ≥18 years Phase 1, DEC and SEC: patients with histologically or cytologically confirmed advanced solid tumor (carcinoma or sarcoma), who have progressive disease, have undergone systemic therapy for advanced disease, and for whom no standard therapy is available Phase 2, EC1: patients with histologically or cytologically confirmed advanced triple-negative breast cancer, who have progressive disease, and have undergone no more than three prior lines of systemic therapy for advanced disease Phase 2, EC2: patients with histologically or cytologically confirmed advanced solid tumor (carcinoma or sarcoma) other than TNBC, who have progressive disease, and have undergone no more than three prior lines of systemic therapy for advanced disease Availability of pretreatment tumor tissue Phase 1, DEC and SEC: at least one measurable or non-measurable lesion as per RECIST v1.1 Phase 2, EC1 and EC2: at least one measurable lesion as per RECIST v1.1 Phase 1, DEC and SEC: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Phase 2, EC1 and EC2: ECOG performance status of 0 or 1 Adequate function of bone marrow, liver, kidneys, heart; adequate coagulation profile Both male and female patients must agree to use effective contraceptive methods Women of child-bearing potential (WCBP) must have a negative serum pregnancy test Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements Exclusion Criteria: Prior treatment with any agent targeting ROR1 Presence of active central nervous system (CNS) metastasis Persistent toxicities from previous systemic anti-neoplastic treatments of Grade > 1 (or Grade > 2 for neurotoxicity) Systemic anti-neoplastic therapy within five half-lives or four weeks (six weeks for nitrosourea and mitomycin-C), whichever is shorter, prior to first dose of the study drug Wide-field radiotherapy within four weeks, or focal radiation for analgesic purpose or for lytic lesions at risk of fracture within two weeks prior to first dose of the study drug, or no recovery from side effects of such intervention Major surgery within four weeks prior to first dose of the study drug, or no recovery from side effects of such intervention Prior allogeneic bone marrow transplantation Significant cardiac disease History of thromboembolic or cerebrovascular events within six months prior to first dose of the study drug Acute and/or clinically significant bacterial, fungal or viral infection Concomitant use of systemic steroids at dose of >10 mg of prednisone or its equivalent per day Concurrent participation in another investigational clinical trial Pregnant or breast-feeding females Other conditions that prevent the patient from giving informed consent or participating in the trial, or that may increase the risk associated with the study participation, or that may interfere with the interpretation of the study results Prior history of malignancy other than inclusion diagnosis within three years prior to first dose of the study drug Prior treatment with cumulative lifetime dose of anthracycline

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation Cohort (DEC)<br>Escalating doses of NBE-002 depending on cohort at enrollment. | Drug: NBE-002<br>* NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.<br>|
| Experimental: Safety-expansion Cohort (SEC)<br>Dose to be determined based on DEC. | Drug: NBE-002<br>* NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.<br>|
| Experimental: Expansion Cohort 1 (EC1)<br>Dose to be determined based on DEC and SEC. | Drug: NBE-002<br>* NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.<br>|
| Experimental: Expansion Cohort 2 (EC2)<br>Dose to be determined based on DEC and SEC. | Drug: NBE-002<br>* NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended Phase 2 Dose (RP2D) (Phase 1) | The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data | Up to 48 months | 
| Anti-tumor Activity (Phase 2) | Anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (Safety and Tolerability) | Safety and tolerability profile will be assessed by Common Terminology Criteria for Adverse Events v5.0 and summarized by type, frequency, and severity of adverse events | Up to 60 months | 
| Preliminary Anti-tumor Activity (Phase 1) | Preliminary anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 | Up to 48 months | 
| Concentrations of NBE-002 | Pharmacokinetic profile will be characterized by concentrations of NBE-002 | Up to 60 months | 
| Concentrations of NBE-002-reactive antibodies | Immunogenicity profile will be characterized by concentrations of NBE-002-reactive antibodies | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ROR1, Antibody-drug Conjugate, Carcinoma, Cancer, Solid Tumor, Sarcoma, Triple Negative Breast Cancer