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

NCT04750239 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 402
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 7

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.

Conditions

SCLC

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLTs) Phase I

  Summary of DLTs in DLT evaluable subjects.

  Days 1 through 28

• Number of Participants With Adverse Events (AEs) for Different Doses of Nivatrotamab in Phase I

  Number of participants with adverse events as a measure of safety and tolerability.

  From first dose until 30 days after last IMP, up to 26 weeks. Actual duration for treated patients were from 21 to 58 days.

Study Arms (1)

Nivatrotamab

EXPERIMENTAL

Subcutaneous administration of nivatrotamab up to 13 cycles

Drug: Nivatrotamab

Interventions

Nivatrotamab DRUG

Anti GD2×CD3 monoclonal bi-specific antibody

Nivatrotamab

Eligibility Criteria

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

You may qualify if:

• 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 partial response or complete response 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.

You may not qualify if:

• Systemic chemotherapy, radiotherapy, immunotherapy, or major surgery administered within 3 weeks prior to the first planned dosing of the investigational Medicinal Product (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%
• Active CNS metastases. Patients with treated central nervous system (CNS) metastases are eligible if they are clinically stable without any new neurological symptoms and if there is no radiological evidence of new or enlarging CNS metastases. CNS-directed treatment (surgery, radiation) must be completed 4 weeks prior to the first IMP administration.
• Furthermore, patients are excluded if they have:
• Leptomeningeal carcinomatosis Uncontrolled seizures. Patients with known seizure are eligible if they are stable and have been without seizure 4 weeks prior to the first IMP administration
• Patients who experienced severe or recurrent (\>grade 2) immune mediated adverse events (AEs) or infusion related reactions (IRRs), including those that lead to permanent discontinuation while on treatment with immune oncology agents

Sponsors & Collaborators

• Y-mAbs Therapeutics: lead

Study Sites (7)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30332, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Limitations and Caveats

The study was terminated after 3 subjects due to a business strategy decision. At this point the maximum tolerated dose was not established. Only 3 subjects at dose level 1 (nivatrotamab 50 mcg) were enrolled.

Results Point of Contact

• Title: Joris Wilms
• Organization: Y-mAbs Therapeutics

clinicaltrials@ymabs.com

+4570261414

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: open-label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label, single-arm, dose-escalation and expansion consisting of up to 13 cycles

Study Record Dates

• First Submitted: February 6, 2021
• First Posted: February 11, 2021
• Study Start: August 17, 2021
• Primary Completion: April 8, 2022
• Study Completion: April 8, 2022
• Last Updated: August 14, 2023
• Results First Posted: August 14, 2023

Record last verified: 2023-06

Locations

US (7)