NBE-002 in Patients With Advanced Solid Tumors

Sponsor

NBE-Therapeutics AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04441099

Collaborator

Cmed Clinical Services (Other)

100

Enrollment

Locations

Arms

65.4

Anticipated Duration (Months)

33.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Advanced Cancer Triple Negative Breast Cancer	Drug: NBE-002	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 19, 2020

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of Adverse Events (Safety and Tolerability) [Up to 60 months]
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
Preliminary Anti-tumor Activity (Phase 1) [Up to 48 months]
Preliminary anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
Concentrations of NBE-002 [Up to 60 months]
Pharmacokinetic profile will be characterized by concentrations of NBE-002
Concentrations of NBE-002-reactive antibodies [Up to 60 months]
Immunogenicity profile will be characterized by concentrations of NBE-002-reactive antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute - TN Oncology	Nashville	Tennessee	United States	37203
2	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
3	NEXT Oncology	San Antonio	Texas	United States	78229