NBE-002 in Patients With Advanced Solid Tumors

NCT04441099 | Terminated Phase 1 FDA Drug

• 1 other identifier: NBE-002-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumor; Advanced Cancer; Triple Negative Breast Cancer

Keywords

ROR1; Antibody-drug Conjugate; Carcinoma; Cancer; Solid Tumor; Sarcoma; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Incidence of Adverse Events (Safety and Tolerability)

  Up to 60 months

• Preliminary Anti-tumor Activity (Phase 1)

  Up to 48 months

• Concentrations of NBE-002

  Up to 60 months

• Concentrations of NBE-002-reactive antibodies

  Up to 60 months

Study Arms (4)

Dose-escalation Cohort (DEC)

EXPERIMENTAL

Escalating doses of NBE-002 depending on cohort at enrollment.

Drug: NBE-002

Safety-expansion Cohort (SEC)

EXPERIMENTAL

Dose to be determined based on DEC.

Drug: NBE-002

Expansion Cohort 1 (EC1)

EXPERIMENTAL

Dose to be determined based on DEC and SEC.

Drug: NBE-002

Expansion Cohort 2 (EC2)

EXPERIMENTAL

Dose to be determined based on DEC and SEC.

Drug: NBE-002

Interventions

NBE-002 DRUG

NBE-002 will be given intravenously on Day 1 of repeated 28-day cycles.

Dose-escalation Cohort (DEC); Expansion Cohort 1 (EC1); Expansion Cohort 2 (EC2); Safety-expansion Cohort (SEC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 treatment with cumulative lifetime dose of anthracycline

Sponsors & Collaborators

• NBE-Therapeutics AG: lead
• Cmed Clinical Services: collaborator

Study Sites (3)

Sarah Cannon Research Institute - TN Oncology

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma; Neoplasms; Sarcoma

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 22, 2020
• Study Start: June 19, 2020
• Primary Completion: August 14, 2023
• Study Completion: August 14, 2023
• Last Updated: September 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)