Clinical trial NCT04441099: NBE-002 in Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Advanced Cancer
Triple Negative Breast Cancer
Keywords: ROR1
Antibody-drug Conjugate
Carcinoma
Cancer
Solid Tumor
Sarcoma
Triple Negative Breast Cancer
Lead sponsor: NBE-Therapeutics AG
Sponsor class: INDUSTRY
Collaborators: name: Cmed Clinical Services
First posted: 2020-06-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) (Phase 1)
timeFrame: Up to 48 months
measure: Anti-tumor Activity (Phase 2)
timeFrame: Up to 60 months
Secondary outcomes:
measure: Incidence of Adverse Events (Safety and Tolerability)
timeFrame: Up to 60 months
measure: Preliminary Anti-tumor Activity (Phase 1)
timeFrame: Up to 48 months
measure: Concentrations of NBE-002
timeFrame: Up to 60 months
measure: Concentrations of NBE-002-reactive antibodies
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - TN Oncology
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
References: