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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04442126
• Other study ID #: NB-ND021 (NM21-1480)-101
• Secondary ID: 2020-0355
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 19, 2020
• Est. completion date: February 6, 2024

Study information

• Verified date: February 2024
• Source: Numab Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: February 6, 2024
• Est. primary completion date: February 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma
• Carcinoma, Squamous Cell
• Colorectal Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Head and Neck Squamous Cell Carcinoma
• Non-small Cell Lung Cancer
• Ovarian Carcinoma
• Peritoneal Carcinoma
• Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• NM21-1480
Trispecific anti-PD-L1/anti-4-1BB/anti-Human Serum Albumin (HSA) single-chain Fv fusion protein

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Numab Therapeutics AG

Countries where clinical trial is conducted

United States,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Frequency and severity of adverse events	Up to 3 years
Primary	Maximum Tolerated Dose (MTD) of NM21-1480	To determine the MTD of NM21-1480	Up to 3 years
Primary	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
Primary	To determine the anti-tumor activity (Best Overall Response) of NM21-1480 according to RECIST 1.1		Up to 3 years
Primary	To determine the anti-tumor activity (Overall Response Rate) of NM21-1480 according to RECIST 1.1		Up to 3 years
Secondary	Assessment of the maximum observed serum concentration determined by direct inspection of the concentration versus time data (Cmax)		Up to 3 years
Secondary	Assessment of the the minimum observed serum concentration determined by direct inspection of the concentration versus time data (Cmin)		Up to 3 years
Secondary	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
Secondary	Assessment of the terminal phase (apparent elimination) rate constant (?z)		Up to 3 years
Secondary	Assessment of the elimination half-life (t½)		Up to 3 years
Secondary	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
Secondary	Assessment of the area under serum concentration-time curve over dosing interval (AUCtau)		Up to 3 years
Secondary	Assessment of the clearance (CL)		Up to 3 years
Secondary	Assessment of the volume of distribution (Vd)		Up to 3 years
Secondary	Assessment of the frequency of specific anti-drug antibodies to NM21-1480		Up to 3 years
Secondary	To determine the anti-tumor activity (Disease Control Rate) of NM21-1480 according to RECIST 1.1		Up to 3 years
Secondary	To determine the anti-tumor activity (Duration of Response) of NM21-1480 according to RECIST 1.1		Up to 3 years
Secondary	To determine the anti-tumor activity (Time-to-response) of NM21-1480 according to RECIST 1.1		Up to 3 years
Secondary	To determine the anti-tumor activity (Progression-free survival) of NM21-1480 according to RECIST 1.1		Up to 3 years
Secondary	To determine the anti-tumor activity (Overall Survival) of NM21-1480 according to RECIST 1.1		Up to 3 years