Safety, Tolerability, and Pharmacokinetics of DCR-PDL1 in Adults With Solid Tumors

Phase 1

Recruiting

• Conditions: Solid Tumors, Adult
• Interventions: Drug: DCR-PDL1

• Registration Number: NCT06504368
• Lead Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-29
• Study First Submitted: 2024-06-18
• Study First Submitted QC: 2024-07-10
• Study First Posted: 2024-07-16
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-06-01
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DCR-PDL1	DCR-PDL1	Participants will receive multiple IV doses of DCR-PDL1 during each treatment cycle.

Primary Outcome Measures

Name	Time	Method
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)	Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Total protein and Albumin	Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Total bilirubin, Direct bilirubin, Fasting blood glucose, Creatinine and Blood urea nitrogen (BUN)	Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Sodium, Chloride and Potassium	Baseline to week 8
Incidence and Nature of Adverse Events (AEs)	Baseline to week 8
Incidence of Dose-limiting Toxicities (DLTs)	Baseline to week 8
Change From Baseline in Vital Signs: Oral, Tympanic, Temporal Artery Temperature	Baseline up to week 8	Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position.
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure	Baseline up to week 8	Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position.
Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate and Pulse Rate	Baseline to week 8
Change from Baseline in Hematology Parameter: Hemoglobin	Baseline to week 8
Change from Baseline in Hematology Parameter: Hematocrit and Mean corpuscular hemoglobin concentration (MCHC)	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Specific Gravity	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Blood	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Ketones and Nitrite	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Leukocyte esterase	Baseline to week 8
Change from Baseline in Coagulation Parameter: Fibrinogen	Baseline to week 8
Change From Baseline in Vital Signs: Pulse and Respiratory Rate	Baseline up to week 8	Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in 12-lead Electrocardiogram (ECG): QRS intervals	Baseline to week 8	ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in Hematology Parameter: Mean corpuscular volume (MCV)	Baseline to week 8
Change from Baseline in Hematology Parameter: Mean corpuscular hemoglobin (MCH)	Baseline to week 8
Change from Baseline in Coagulation Parameter: International normalized ratio (INR)	Baseline to week 8
Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals	Baseline to week 8	ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula)	Baseline to week 8	ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in Hematology Parameter: Red blood cells, White blood cells, Lymphocytes, Monocytes, Eosinophils, Neutrophils, Basophils and Platelets, Reticulocytes	Baseline to week 8
Change from Baseline in Coagulation Parameter: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Glucose, Protein, Bilirubin and Urobilinogen	Baseline to week 8
Change from Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) of Urine	Baseline to week 8
Number of Participants with Change from Baseline in Physical Examination Findings: Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems	Baseline to week 8	A complete physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic Plasma Concentrations of DCR-PDL1	Pre-dose up to 48 hours post-dose
Pharmacokinetic Urine Concentrations of DCR-PDL1	Up to 8 hours post-dose

Trial Locations

Locations (1)

Next Oncology; 🇺🇸 San Antonio, Texas, United States