Clinical trial NCT04442126: A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Non-small Cell Lung Cancer
Colorectal Cancer
Squamous Cell Carcinoma
Ovarian Carcinoma
Peritoneal Carcinoma
Fallopian Tube Cancer
Head and Neck Squamous Cell Carcinoma
Triple Negative Breast Cancer
Keywords: Carcinoma
Neoplasms
Lead sponsor: Numab Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2020-06-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Maximum Tolerated Dose (MTD) of NM21-1480
timeFrame: Cycle 1 (28 days).
measure: Determination of Phase 2 Dose of NM21-1480
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: To Determine the Anti-tumor Activity (Best Overall Response) of NM21-1480 According to RECIST 1.1
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Secondary outcomes:
measure: Assessment of the Maximum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmax)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the the Minimum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmin)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Time From Dosing at Which Cmax is Apparent Determined by Direct Inspection of the Concentration Versus Time Data (Tmax)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Terminal Phase (Apparent Elimination) Rate Constant (λz)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Elimination Half-life (t½)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Area Under the Serum Concentration-time Curve Extrapolated From the Last Quantifiable Concentration to Infinity Quantifiable Concentration to Infinity (AUC[0-infinity])
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Area Under Serum Concentration-time Curve Over Dosing Interval (AUCtau)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Clearance (CL)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Volume of Distribution (Vd)
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: Assessment of the Frequency of Specific Anti-drug Antibodies to NM21-1480
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: To Determine the Anti-tumor Activity (Duration of Response) of NM21-1480 According to RECIST 1.1
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: To Determine the Anti-tumor Activity (Time-to-response) of NM21-1480 According to RECIST 1.1
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
measure: To Determine the Anti-tumor Activity (Progression-free Survival) of NM21-1480 According to RECIST 1.1
timeFrame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: UCHealth Poudre Valley Hospital
state: Colorado
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Cancer Center
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University Of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: A Coruña
country: Spain
facility: Hospital Universitario de A Coruna
city: Barcelona
country: Spain
facility: Hospital Universitario Vall dHebron
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaen
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Llatzer
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: