A Study of DCR-STAT3 in Adults With Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

An Open-label, Phase 1, Dose-ranging Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous DCR-STAT3 in Adults With Refractory Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06098651
• Other study ID #: DCR-STAT3-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 14, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: October 2023
• Source: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Contact: Vinita Uttamsingh
• Phone: 857-278-9860
• Email: VIUT[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a sequential, ascending-dose, multicenter study conducted in patients with refractory solid tumors designed to evaluate the safety, tolerability, and pharmacokinetics of DCR-STAT3.

Description:

The primary goal of this first-in-human study is to assess the safety and tolerability of DCR-STAT3 in adults with refractory solid tumors. Secondary study goals are to evaluate potential antitumor effects of STAT3 knockdown, as assessed by circulating blood biomarkers indicative of immune activation, as well as any direct impact on tumor size by appropriate imaging and RECIST 1.1 criteria. Antitumor effects will be evaluated for DCR-STAT3 as a monotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age

• = 18 years of age inclusive, at the time of signing the informed consent.

Type of Participant and Disease Characteristics

• 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 for which no standard therapy is available

• Demonstrated evidence of disease progression, via imaging, during or following standard therapy known to provide clinical benefit for their condition

• Demonstrated intolerance to standard therapy known to provide clinical benefit for their condition

• Measurable disease according to RECIST version 1.1 (as determined by CT or MRI)

• Malignancy not currently amenable to surgical intervention due to medical contraindication or non-resectability of the tumor

• ECOG performance status of 0, 1, or 2, and an anticipated life expectancy of = 3 months

Weight

• BMI = 18 kg/m2

Sex

Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 24 weeks after the last dose of study intervention:

1. Refrain from donating sperm

AND, either:

2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR

3. Must agree to use a male condom when having sexual intercourse with a WOCBP who is not currently pregnant

Female participants are eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:

1. Is not a WOCBP OR

2. Is a WOCBP and:

is using a contraceptive method that is highly effective, with a failure rate of < 1%, as described in Section 10.4 during the study intervention period and for at least 24 weeks after the last dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

must have a negative highly sensitive pregnancy test (serum as required by local regulations) on Day 1 of each cycle before the first dose of study intervention

Exclusion Criteria:

Prior/Concomitant Therapy

• Other concurrent (within 28 days of Day 1, Cycle 1) chemotherapy, immunotherapy, or radiotherapy. Note that hormonal therapy (e.g., tamoxifen, LHRH agonists) is allowed.

• Requirement for palliative radiotherapy to lesions that are defined as target lesions by RECIST version 1.1 criteria at the time of study entry

• Continued compromise or inadequate recovery from a prior anti-neoplastic therapy

• Known hypersensitivity to any of the components of DCR-STAT3

• Long-term immunosuppressive therapy

Prior/Concurrent Clinical Study Experience

• Treatment with investigational therapy(ies) within 5 half-lives of the investigational therapy prior to the first scheduled day of dosing with DCR-STAT3, or 4 weeks if the half-life of the investigational agent is not known

Diagnostic assessments - Seropositive for antibodies to HIV, HBV, or HCV at Screening (historical testing may be used if performed within the 3 months prior to screening). NOTE: In participants with previous treatment for hepatitis C with direct-acting HCV medication and seropositivity for HCV, or in participants with prior infection and spontaneous resolution, HCV RNA must be undetectable (at least 2 negative HCV RNA tests at least 12 weeks apart), and the HCV infection must have been resolved or cured > 3 years prior to initial dosing with the investigational medication.

Related Conditions & MeSH terms

• Neoplasms
• Refractory Tumor
• Solid Tumor, Adult

Intervention

Drug:
• DCR-STAT3
DCR-STAT3 is a sterile, preservative-free solution in WFI that will be diluted in a suitable admixture diluent (0.9% normal saline) prior to IV infusion.

Locations

Country	Name	City	State
United States	Next Oncology	Dallas	Texas
United States	Next Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events and dose limiting toxicities	safety and tolerability	Cycle 1 (8 weeks)
Primary	Severity of adverse events	measured according to CTCAE 5.0 criteria	Cycle 1 (8 weeks)
Secondary	Pharmacokinetic (AUC)	Area under the plasma concentration versus time curve	Day 1 and Day 29 of Cycle 1 (each cycle is 8 weeks)
Secondary	Pharmacokinetic (Urine)	Urinary excretion	Day 1 and Day 29 of Cycle 1 (each cycle is 8 weeks)