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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Numab Therapeutics AG
- Enrollment
- 52
- Locations
- 26
- Primary Endpoint
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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.
Arms & Interventions
NM21-1480 Treatment arm
Intervention: NM21-1480 (Biological)
Outcomes
Primary Outcomes
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
Time Frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
Frequency and severity of adverse events
Maximum Tolerated Dose (MTD) of NM21-1480
Time Frame: Cycle 1 (28 days).
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.
Determination of Phase 2 Dose of NM21-1480
Time Frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
To determine the recommended Phase 2 dose of NM21-1480 for Part B of the study
To Determine the Anti-tumor Activity (Best Overall Response) of NM21-1480 According to RECIST 1.1
Time Frame: From baseline to up to 12 weeks post last dose, up to 48 weeks.
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.
Secondary Outcomes
- Assessment of the Maximum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmax)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the the Minimum Observed Serum Concentration Determined by Direct Inspection of the Concentration Versus Time Data (Cmin)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Time From Dosing at Which Cmax is Apparent Determined by Direct Inspection of the Concentration Versus Time Data (Tmax)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Terminal Phase (Apparent Elimination) Rate Constant (λz)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Elimination Half-life (t½)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- 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])(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Area Under Serum Concentration-time Curve Over Dosing Interval (AUCtau)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Clearance (CL)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Volume of Distribution (Vd)(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- Assessment of the Frequency of Specific Anti-drug Antibodies to NM21-1480(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- To Determine the Anti-tumor Activity (Duration of Response) of NM21-1480 According to RECIST 1.1(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- To Determine the Anti-tumor Activity (Progression-free Survival) of NM21-1480 According to RECIST 1.1(From baseline to up to 12 weeks post last dose, up to 48 weeks.)
- To Determine the Anti-tumor Activity (Time-to-response) of NM21-1480 According to RECIST 1.1(From baseline to up to 12 weeks post last dose, up to 48 weeks.)