A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors

A Phase 1/2 Study of NM21-1480 (Anti-PDL-1/Anti-4-1BB/Anti-HSA Tri-Specific Antibody) in Adult Patients With Advanced Solid Tumors

This is a first-in-human, open-label, multi-center, Phase 1/2, dose-escalation study with expansion cohorts to evaluate NM21-1480 for safety and immunogenicity, to determine the maximal tolerated dose and recommended Phase 2 dose, define the pharmacokinetics, to explore the pharmacodynamics, and to obtain preliminary evidence of the clinical activity in adult patients with selected advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Fallopian Tube Cancer; Triple Negative Breast Cancer; Advanced Solid Tumor; Non-small Cell Lung Cancer; Peritoneal Carcinoma; Head and Neck Squamous Cell Carcinoma; Ovarian Carcinoma; Squamous Cell Carcinoma
• Intervention / Treatment: Biological: NM21-1480

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Peter Lichtlen, MD, PhD, BBA; Phone Number: +41-44-533-22-92; Email: clinicaltrials@numab.com

Study Locations

• Spain
  • A Coruña, Spain
    • Hospital Universitario de A Coruna
  • Barcelona, Spain
    • Hospital Universitario Vall Dhebron
  • Elche, Spain
    • Hospital General Universitario de Elche
  • Jaén, Spain
    • Complejo Hospitalario de Jaen
  • Madrid, Spain
    • Centro Integral Oncológico Clara Campal
  • Madrid, Spain
    • Clinica Universidad de Navarra - Madrid
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Palma De Mallorca, Spain
    • Hospital Universitario Son Llatzer
  • Pamplona, Spain
    • Clinica Universidad de Navarra - Pamplona
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • UCHealth Poudre Valley Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Ypsilanti, Michigan, United States, 48197
      • St. Joseph Mercy Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Cancer Center
  • New York
    • Bronx, New York, United States, 10461-2374
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Part A

• Patients with any previously treated solid tumor-type other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma that is advanced, or recurrent and progressing since last anti-tumor therapy, and for which no alternative, standard therapy exists.
• Prior chemotherapy, radiation therapy or immunotherapy must have been completed at least 4 weeks prior to the administration of the first dose of study drug, and patient has recovered

Part B:

• Patients with Non-small Cell Lung Cancer (NSCLC) or other protocol specified solid tumors with locally advanced or metastatic, non-resectable disease, which has progressed despite treatment with first-line standard of-care treatment, or first- and second-line treatment, dependent on expansion cohort.
• Prior therapy must have been completed 2-4 weeks prior to the administration of the first dose of study drug as specified per protocol according to type of prior therapy

Exclusion Criteria:

• Patient previously had known immediate or delayed hypersensitivity reaction or idiosyncrasy to the excipients
• Part A: Treatment with any PD-1, or Cytotoxic T-Lymphocyte Associated Protein (CTLA)-4 directed antibody, or with any other immunotherapy within 4 weeks prior to initiation of the study drug.
• Part A: Use of other biological investigational drugs (drugs not marketed for any indication), including use of investigational drugs targeting CD137/4-1BB within at least 5 half-lives (or within 8 weeks, whatever is longer) prior to the administration of the first dose of study drug.
• Part B: As defined per protocol for each expansion cohort, has not been treated with specified first/second-line standard-of-care therapies biological drugs (marketed or investigational) for treatment of the current cancer, or has not adequately recovered from AEs that occurred with prior therapy.
• Patient has an active autoimmune disease or a documented history of autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NM21-1480 Treatment arm	Biological: NM21-1480; Trispecific anti-PD-L1/anti-4-1BB/anti-Human Serum Albumin (HSA) single-chain Fv fusion protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Frequency and severity of adverse events	Up to 3 years
Maximum Tolerated Dose (MTD) of NM21-1480	To determine the MTD of NM21-1480	Up to 3 years
Determination of Phase 2 dose of NM21-1480	To determine the recommended Phase 2 dose of NM21-1480 for Part B of the study	Up to 3 years
To determine the anti-tumor activity (Best Overall Response) of NM21-1480 according to RECIST 1.1		Up to 3 years
To determine the anti-tumor activity (Overall Response Rate) of NM21-1480 according to RECIST 1.1		Up to 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of the maximum observed serum concentration determined by direct inspection of the concentration versus time data (Cmax)	Up to 3 years
Assessment of the the minimum observed serum concentration determined by direct inspection of the concentration versus time data (Cmin)	Up to 3 years
Assessment of the time from dosing at which Cmax is apparent determined by direct inspection of the concentration versus time data (Tmax)	Up to 3 years
Assessment of the terminal phase (apparent elimination) rate constant (λz)	Up to 3 years
Assessment of the elimination half-life (t½)	Up to 3 years
Assessment of the area under the serum concentration-time curve extrapolated from the last quantifiable concentration to infinity (AUC[0-infinity])	Up to 3 years
Assessment of the area under serum concentration-time curve over dosing interval (AUCtau)	Up to 3 years
Assessment of the clearance (CL)	Up to 3 years
Assessment of the volume of distribution (Vd)	Up to 3 years
Assessment of the frequency of specific anti-drug antibodies to NM21-1480	Up to 3 years
To determine the anti-tumor activity (Disease Control Rate) of NM21-1480 according to RECIST 1.1	Up to 3 years
To determine the anti-tumor activity (Duration of Response) of NM21-1480 according to RECIST 1.1	Up to 3 years
To determine the anti-tumor activity (Time-to-response) of NM21-1480 according to RECIST 1.1	Up to 3 years
To determine the anti-tumor activity (Progression-free survival) of NM21-1480 according to RECIST 1.1	Up to 3 years
To determine the anti-tumor activity (Overall Survival) of NM21-1480 according to RECIST 1.1	Up to 3 years

Collaborators and Investigators

• Sponsor: Numab Therapeutics AG

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2020
• Primary Completion (Actual): February 6, 2024
• Study Completion (Actual): February 6, 2024

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Carcinoma; Neoplasms
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Adnexal Diseases; Breast Diseases; Head and Neck Neoplasms; Fallopian Tube Diseases; Neoplasms, Squamous Cell; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Fallopian Tube Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms
• Other Study ID Numbers: NB-ND021 (NM21-1480)-101; 2020-0355 (Other Identifier: MDACC Protocol ID)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No