Clinical Trials /

Safety and Clinical Activity of Nivatrotamab in Relapsed/Recurrent Metastatic Small-cell Lung Cancer

NCT04750239

Description:

Adult patients with small-cell lung cancer (SCLC) will be treated with nivatrotamab a monoclonal anti GD2×CD3 bispecific antibody to investigate the safety and tolerability of the drug.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Clinical Activity of Nivatrotamab in Relapsed/Recurrent Metastatic Small-cell Lung Cancer
  • Official Title: Safety and Clinical Activity of Nivatrotamab, an Anti GD2×CD3 Bispecific Antibody, in Relapsed/Recurrent Metastatic Small-cell Lung Cancer An Open-label, Single-arm, Multicenter, Phase 1/2 Trial

Clinical Trial IDs

  • ORG STUDY ID: 402
  • NCT ID: NCT04750239

Conditions

  • SCLC

Interventions

DrugSynonymsArms
NivatrotamabNivatrotamab

Purpose

Adult patients with small-cell lung cancer (SCLC) will be treated with nivatrotamab a monoclonal anti GD2×CD3 bispecific antibody to investigate the safety and tolerability of the drug.

Detailed Description

      The study will include a phase 1 dose escalation part to determine the maximum tolerated dose
      (MTD) and the recommended phase 2 dose (RP2D). This will be conducted following a modified
      Bayesian Optimal Interval Design (mBOIN) design. For the purpose of dose escalation,
      dose-limiting toxicities (DLTs) will be collected and assessed for a period of 28 days (the
      DLT evaluation period).

      A phase 2 dose expansion part will follow the phase 1 dose escalation. In phase 2, patients
      will be stratified according to whether they have platinum sensitive or platinum-resistant
      SCLC. Phase 2 will assess the long term safety and tolerability of nivatrotamab as well as
      the clinical activity of nivatrotamab when administered at the obtained MTD/RP2D in phase 1.
    

Trial Arms

NameTypeDescriptionInterventions
NivatrotamabExperimentalSubcutaneous administration of nivatrotamab up to 13 cycles
  • Nivatrotamab

Eligibility Criteria

        Inclusion Criteria:

          -  Signed and dated informed consent has been provided prior to any trial-related
             procedures.

          -  Patient willing and able to comply with the trial protocol

          -  Age ≥18 years at the time of informed consent

          -  Histologically or cytologically proven SCLC. Radiographical relapse/progression after
             minimum 1 line of platinum-containing chemotherapy with PR or CR as the best response
             (only applicable for phase 2) and not more than 3 prior lines of therapy

          -  Measurable disease according to RECIST v1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Expected survival >3 months

          -  Platelet counts ≥100,000 cells/mm3

          -  Hemoglobin ≥9 g/dL

          -  Absolute neutrophil count (ANC) ≥1000 cells/mm3

          -  Adequate liver function defined by aspartate aminotransferase (AST), alanine
             aminotransferase (ALT), alkaline phosphatase (ALP) ≤3 × upper limit of normal (ULN),
             and serum bilirubin ≤1.5 × ULN with the following exceptions

          -  In patients with documented liver metastases, AST, ALT, and ALP ≤5 × ULN and serum
             bilirubin ≤1.5 × ULN

          -  Adequate renal function with serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50
             mL/min as calculated using the Cockcroft Gault equation

          -  Serum albumin >3.0 g/dL

          -  Women of child-bearing potential must agree to appropriate contraception during
             treatment and for a period of 30 days after the last dose of study drug.

        Exclusion Criteria:

          -  Systemic chemotherapy, radiotherapy, immunotherapy, or major surgery administered
             within 3 weeks prior to the first planned dosing of the IMP per protocol

          -  Patients receiving any other investigational therapy for their cancer within 3 weeks
             prior to the first planned dosing of the IMP per protocol

          -  Patients who never received platinum-containing regimen for SCLC (defined as less than
             2 cycles of platinum doublet)

          -  Persistent > grade 1 toxicity from previous treatment with checkpoint inhibitors

          -  Any immunosuppressive concomitant medication (i.e., salazopyrine, methotrexate,
             steroids etc.)

          -  Inability to wean off steroid, unless tapered to 0 mg/day minimum 10 days prior to the
             first treatment in case of prior use

          -  Any active, uncontrolled viral, fungal, or bacterial infection

          -  Any medical history within 3 months prior to enrolment with need for anticonvulsant
             therapy

          -  Patients with diagnosis of autoimmune diseases or immunodeficiencies or documented
             infection with human immunodeficiency virus (HIV) or hepatitis B or C virus (active)

          -  Previous autologous stem cell transplantation or solid organ transplantation

          -  Active heart disease including myocardial infarction within the last 6 months before
             first dose. This includes cardiac insufficiency with left ventricular ejection
             fraction (LVEF) <50%

          -  Patients with CNS metastasis unless fulfilling all the following:

               1. maximum number of metastasis is 3 (leptomeningeal disease is not allowed)

               2. all foci must be subcentimeter on MRI

               3. all foci must have received prior radiation therapy, Whole Brain Radiotherapy
                  (WBRT) and/or Stereotactic Radiosurgery (SRS) and must be stable

               4. no history of seizures

          -  Patients who experienced severe or recurrent (>grade 2) immune mediated AEs or IRRs,
             including those that lead to permanent discontinuation while on treatment with immune
             oncology agents

          -  Prior treatment with anti-GD2 antibody or bispecific antibodies

          -  Patients with Limited Disease (LD), who are candidates for local or regional therapy.

          -  Impending need for palliative radiotherapy or surgery for pathological fractures
             and/or for medullary compression up to 3 weeks prior to the first planned dosing of
             the IMP per protocol (palliative radiation for other reasons within 2 weeks)

          -  History of other active malignancy within the past 3 years prior to the first planned
             dosing of the IMP per protocol (excluding non-melanoma skin cancers, carcinoma in situ
             of the cervix, ductal carcinoma in situ of the breast, incidental prostate cancer
             (T1a, Gleason score ≤ 6, prostate specific antigen (PSA) less than 0.5 ng/ml)

          -  Patients with a significant intercurrent illness (any ongoing serious medical problem
             unrelated to cancer or its treatment) that is not covered by the detailed exclusion
             criteria and that is expected to interfere with the action of the trial IMP or
             significantly increase the severity of the toxicities experienced from trial treatment

          -  Patients who are pregnant or breastfeeding

          -  Patients with a body weight of < 45 kg

          -  Patients with prior orthostatic hypotension
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the MTD and the RP2D of nivatrotamab
Time Frame:28 days
Safety Issue:
Description:The MTD (defined by a modified Bayesian Optimal Interval Design [mBOIN]) and the RP2D of nivatrotamab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Y-mAbs Therapeutics

Last Updated

August 16, 2021