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

Study Overview
=================
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.

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

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

Intervention / Treatment
-----------------
* Biological: NM21-1480


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carcinoma, Neoplasms