Clinical trial NCT06504368: Safety, Tolerability, and Pharmacokinetics of DCR-PDL1 in Adults With Solid Tumors
Official title: An Open-Label, Phase 1, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous DCR-PDL1 in Adults With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors, Adult
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2024-07-16
Enrollment: 32
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: The study will evaluate the safety, tolerability, and pharmacokinetics of intravenous DCR-PDL1 in adults with solid tumors. Participants will be enrolled in one of 4 ascending-dose cohorts. Each treatment cycle will consist of multiple intravenous (IV) doses. Dose escalation decisions will be based on data collected during the dose-limiting toxicity (DLT) period.


Eligibility criteria: Inclusion Criteria:

* Male or female adults, aged greater than or equal to (≥) 18 years.
* Participants are required to have a documented, locally advanced or metastatic solid tumor malignancy, or non-Hodgkin's lymphoma

  * that is refractory to standard therapy known to provide clinical benefit for their condition OR
  * have demonstrated evidence of disease progression or relapse, via imaging, during or following standard therapy known to provide clinical benefit for their condition, OR
  * have demonstrated intolerance to standard therapy known to provide clinical benefit for their condition. OR
  * for which no standard therapy is available
* Measurable disease according to RECIST version 1.1.
* Malignancy not currently amenable to surgical intervention.
* ECOG performance status of 0, 1, or 2, and an anticipated life expectancy of ≥ 3 months at the time of signing the informed consent.
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants with known CNS or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required.
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Incidence and Nature of Adverse Events (AEs)
timeFrame: Baseline to week 8
measure: Incidence of Dose-limiting Toxicities (DLTs)
timeFrame: Baseline to week 8
measure: Change From Baseline in Vital Signs: Oral, Tympanic, Temporal Artery Temperature
timeFrame: Baseline up to week 8
measure: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure
timeFrame: Baseline up to week 8
measure: Change From Baseline in Vital Signs: Pulse and Respiratory Rate
timeFrame: Baseline up to week 8
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate and Pulse Rate
timeFrame: Baseline to week 8
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QRS intervals
timeFrame: Baseline to week 8
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals
timeFrame: Baseline to week 8
measure: Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula)
timeFrame: Baseline to week 8
measure: Change from Baseline in Hematology Parameter: Red blood cells, White blood cells, Lymphocytes, Monocytes, Eosinophils, Neutrophils, Basophils and Platelets, Reticulocytes
timeFrame: Baseline to week 8
measure: Change from Baseline in Hematology Parameter: Mean corpuscular volume (MCV)
timeFrame: Baseline to week 8
measure: Change from Baseline in Hematology Parameter: Mean corpuscular hemoglobin (MCH)
timeFrame: Baseline to week 8
measure: Change from Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline to week 8
measure: Change from Baseline in Hematology Parameter: Hematocrit and Mean corpuscular hemoglobin concentration (MCHC)
timeFrame: Baseline to week 8
measure: Change from Baseline in Coagulation Parameter: International normalized ratio (INR)
timeFrame: Baseline to week 8
measure: Change from Baseline in Coagulation Parameter: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)
timeFrame: Baseline to week 8
measure: Change from Baseline in Coagulation Parameter: Fibrinogen
timeFrame: Baseline to week 8
measure: Change from Baseline in Clinical Chemistry Parameter: Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and Creatine kinase (CK)
timeFrame: Baseline to week 8
measure: Change from Baseline in Clinical Chemistry Parameter: Total protein and Albumin
timeFrame: Baseline to week 8
measure: Change from Baseline in Clinical Chemistry Parameter: Total bilirubin, Direct bilirubin, Fasting blood glucose, Creatinine and Blood urea nitrogen (BUN)
timeFrame: Baseline to week 8
measure: Change from Baseline in Clinical Chemistry Parameter: Sodium, Chloride and Potassium
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Glucose, Protein, Bilirubin and Urobilinogen
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Specific Gravity
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) of Urine
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Blood
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Ketones and Nitrite
timeFrame: Baseline to week 8
measure: Change from Baseline in Urinalysis Parameter: Leukocyte esterase
timeFrame: Baseline to week 8
measure: Number of Participants with Change from Baseline in Physical Examination Findings: Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems
timeFrame: Baseline to week 8
Secondary outcomes:
measure: Pharmacokinetic Plasma Concentrations of DCR-PDL1
timeFrame: Pre-dose up to 48 hours post-dose
measure: Pharmacokinetic Urine Concentrations of DCR-PDL1
timeFrame: Up to 8 hours post-dose
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: