Clinical Trials /

NBE-002 in Patients With Advanced Solid Tumors

NCT04441099

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Carcinoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NBE-002-01
  • NCT ID: NCT04441099

Conditions

  • Advanced Solid Tumor
  • Advanced Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
NBE-002Dose-escalation Cohort (DEC)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose-escalation Cohort (DEC)ExperimentalEscalating doses of NBE-002 depending on cohort at enrollment.
  • NBE-002
Safety-expansion Cohort (SEC)ExperimentalDose to be determined based on DEC.
  • NBE-002
Expansion Cohort 1 (EC1)ExperimentalDose to be determined based on DEC and SEC.
  • NBE-002
Expansion Cohort 2 (EC2)ExperimentalDose to be determined based on DEC and SEC.
  • NBE-002

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) (Phase 1)
Time Frame:Up to 15 months
Safety Issue:
Description:The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data

Secondary Outcome Measures

Measure:Incidence of Adverse Events (Safety and Tolerability)
Time Frame:Up to 36 months
Safety Issue:
Description: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
Measure:Preliminary Anti-tumor Activity (Phase 1)
Time Frame:Up to 15 months
Safety Issue:
Description:Preliminary anti-tumor activity will be assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
Measure:Concentrations of NBE-002
Time Frame:Up to 36 months
Safety Issue:
Description:Pharmacokinetic profile will be characterized by concentrations of NBE-002
Measure:Concentrations of NBE-002-reactive antibodies
Time Frame:Up to 36 months
Safety Issue:
Description:Immunogenicity profile will be characterized by concentrations of NBE-002-reactive antibodies

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NBE-Therapeutics AG

Trial Keywords

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

Last Updated

June 18, 2020