NBE-002 in Patients With Advanced Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Cancer; Advanced Solid Tumor; Advanced Cancer
• Intervention / Treatment: Drug: NBE-002

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - TN Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NBE-Therapeutics AG
• Collaborators: Cmed Clinical Services

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2020
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Carcinoma; Solid Tumor; Triple Negative Breast Cancer; ROR1; Sarcoma; Antibody-drug Conjugate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: NBE-002-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No