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.
Brief Title
A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors
Categories
Completion Date
Completion Date Type
Actual
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
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.
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.
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
Carcinoma
Neoplasms
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04442126
Org Class
Industry
Org Full Name
Numab Therapeutics AG
Org Study Id
NB-ND021 (NM21-1480)-101
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Frequency and severity of adverse events
Outcome Measure
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Description
To determine the MTD of NM21-1480 based on Part A. Note, No MTD was identified across all dose levels tested and a technical MTD was defined by the SMC as 800 mg following Part A, which was updated to 1400 mg by the SMC after completion of Part A-2.
Outcome Measure
Maximum Tolerated Dose (MTD) of NM21-1480
Outcome Time Frame
Cycle 1 (28 days).
Outcome Description
To determine the recommended Phase 2 dose of NM21-1480 for Part B of the study
Outcome Measure
Determination of Phase 2 Dose of NM21-1480
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Description
For best overall response (BOR) and objective response rate (ORR), patients in the Efficacy Analysis Set (EAS) who did not have sufficient on-study tumor assessments to characterize response were included in the denominator when calculating BOR percent and ORR and were thus treated as non-responders.
Outcome Measure
To Determine the Anti-tumor Activity (Best Overall Response) of NM21-1480 According to RECIST 1.1
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Secondary Ids
Secondary Id
2020-0355
Secondary Outcomes
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Maximum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmax)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the the Minimum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmin)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Time From Dosing at Which Cmax is Apparent Determined by Direct Inspection of the Concentration Versus Time Data (Tmax)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Terminal Phase (Apparent Elimination) Rate Constant (λz)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Elimination Half-life (t½)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome 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])
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Area Under Serum Concentration-time Curve Over Dosing Interval (AUCtau)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Clearance (CL)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Volume of Distribution (Vd)
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
Assessment of the Frequency of Specific Anti-drug Antibodies to NM21-1480
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
To Determine the Anti-tumor Activity (Duration of Response) of NM21-1480 According to RECIST 1.1
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
To Determine the Anti-tumor Activity (Time-to-response) of NM21-1480 According to RECIST 1.1
Outcome Time Frame
From baseline to up to 12 weeks post last dose, up to 48 weeks.
Outcome Measure
To Determine the Anti-tumor Activity (Progression-free Survival) of NM21-1480 According to RECIST 1.1
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org