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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04750239
Recruitment Status : Recruiting
First Posted : February 11, 2021
Last Update Posted : September 27, 2021
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
SCLC Drug: Nivatrotamab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 69 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: open-label, single-arm, dose-escalation and expansion consisting of up to 13 cycles
Masking: None (Open Label)
Masking Description: open-label
Primary Purpose: Treatment
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
Actual Study Start Date : August 17, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Nivatrotamab
Subcutaneous administration of nivatrotamab up to 13 cycles
Drug: Nivatrotamab
Anti GD2×CD3 monoclonal bi-specific antibody

Primary Outcome Measures :
  1. To determine the MTD and the RP2D of nivatrotamab [ Time Frame: 28 days ]
    The MTD (defined by a modified Bayesian Optimal Interval Design [mBOIN]) and the RP2D of nivatrotamab

  2. The overall incidence and severity of adverse events (AEs) for different doses of nivatrotamab in phase I [ Time Frame: 26 weeks ]
    Number of participants with adverse events as a measure of safety and tolerability

  3. Incidence and severity of AEs for nivatrotamab dosed at RP2D [ Time Frame: 26 weeks ]
    Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04750239

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Contact: Joris Wilms +4570261414

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United States, Florida
Moffitt Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30332
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
Fox Chase Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111
UPMC Hillman Cancer Center Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Y-mAbs Therapeutics
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Responsible Party: Y-mAbs Therapeutics Identifier: NCT04750239    
Other Study ID Numbers: 402
First Posted: February 11, 2021    Key Record Dates
Last Update Posted: September 27, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Small Cell Lung Carcinoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases