DCR-STAT3 for Cancer

No longer recruiting at 1 trial location

Overseen By Vinita Uttamsingh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: HIV, HBV, HCV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DCR-STAT3 for individuals with advanced or hard-to-treat solid tumors or non-Hodgkin's lymphoma that have not responded to other treatments. The main goal is to assess the safety and tolerability of DCR-STAT3 and to understand its behavior in the body. Individuals with tumors that cannot be surgically removed and whose disease has progressed despite standard treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have other chemotherapy, immunotherapy, or radiotherapy within 28 days of starting the trial. Hormonal therapy is allowed.

Is there any evidence suggesting that DCR-STAT3 is likely to be safe for humans?

Research shows that DCR-STAT3 is in early testing stages, designed for patients with hard-to-treat solid tumors. The study primarily focuses on assessing the treatment's safety and tolerability. Although detailed safety information is limited, experts closely monitor the treatment to ensure participant safety.

DCR-STAT3 blocks a protein that aids cancer growth. Similar treatments targeting this protein have been studied and can sometimes reduce tumor recurrence. However, since DCR-STAT3 remains in the first testing phase, more data is needed to fully understand its safety in humans. Treatments in this phase are closely monitored to determine the right dose and identify any side effects.

In summary, while DCR-STAT3 shows promise, further research is necessary to confirm patient tolerability. Trial participants will help gather this crucial safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DCR-STAT3 is unique because it targets the STAT3 protein, which is often overactive in various cancers and contributes to tumor growth and survival. Unlike traditional treatments that might focus on killing cancer cells more broadly, DCR-STAT3 aims to specifically disrupt this problematic signaling pathway, potentially leading to fewer side effects and more precise targeting of cancer cells. Researchers are excited about DCR-STAT3 because it offers a novel mechanism of action that could complement or enhance existing therapies, opening up new avenues for treating patients who may not respond well to current options.

What evidence suggests that DCR-STAT3 might be an effective treatment for cancer?

Research has shown that DCR-STAT3 targets a protein that aids cancer growth. By blocking this protein, DCR-STAT3 may shrink tumors or halt their growth. This treatment targets a specific part of the protein called STAT3, crucial for cancer cell growth and survival. Early studies suggest that targeting STAT3 can effectively treat cancer. Although more information is needed, these findings offer hope that DCR-STAT3 could be a promising treatment for individuals with difficult-to-treat solid tumors. ^{1 2 3 4 6}

Who Is on the Research Team?

John Hanrahan, MD MPH

Principal Investigator

Dicerna Phamaceuticals, a Novo Nordisk Company

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors or non-Hodgkin's lymphoma that can't be surgically removed and haven't responded to standard treatments. Participants must not be pregnant, agree to contraception, have a life expectancy of at least 3 months, and an ECOG status of 0-2 (able to perform daily activities). They cannot join if they've had certain recent treatments or are HIV/HBV/HCV positive.

Inclusion Criteria

My cancer is advanced and hasn't responded to standard treatments.

My condition worsened after treatment that usually works.

I cannot tolerate the standard treatment for my condition.

Exclusion Criteria

Known hypersensitivity to any of the components of DCR-STAT3

I haven't fully recovered from side effects of previous cancer treatment.

I have tested positive for HIV, HBV, or HCV but meet specific conditions if treated for HCV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DCR-STAT3 as a monotherapy in a dose-ranging study to evaluate safety, tolerability, and pharmacokinetics

8 weeks

Visits on Day 1 and Day 29 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DCR-STAT3

Trial Overview

The trial is testing DCR-STAT3, a new drug for people with solid tumors that no longer respond to usual treatment. It's given in increasing doses to check its safety and how the body processes it. The study will gradually enroll more patients as it confirms lower doses are safe.

How Is the Trial Designed?

Group I: DCR-STAT3 Experimental Treatment 1 Intervention

DCR-STAT3

Who Is Running the Clinical Trial?

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Lead Sponsor

Trials

19

Recruited

580+

Published Research Related to This Trial

The STAT3 pathway plays a key role in creating immunosuppressive environments around tumors, which can hinder the effectiveness of immune cells and promote tumor growth.

Targeting the STAT3 oncogenic pathway presents a promising new strategy for cancer immunotherapy, potentially reversing the immunosuppressive effects and enhancing the body's ability to fight tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing. Dong, Y., Chen, J., Chen, Y., et al.[2023]

The combination of STAT3 antisense oligonucleotide (STAT3 AS-ON) and DDP (cisplatin) significantly inhibits the growth of laryngeal cancer cells (Hep-2) and induces apoptosis, with the highest apoptosis rate observed at 32.9% in the combined treatment group after 72 hours.

STAT3 AS-ON effectively reduces the expression and phosphorylation of the STAT3 protein, leading to a shift in the cell cycle that favors apoptosis, suggesting that targeting the STAT3 signaling pathway could be a promising new strategy for laryngeal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular mechanisms involved in regulation of proliferation and apoptosis by STAT3 antisense oligonucleotide and chemotherapy in laryngeal cancer cells]. Wang, JG., Li, XM., Chen, YH., et al.[2013]

Constitutive activation of STAT3 is commonly found in many human tumors, including various hematological malignancies and solid tumors, and it plays a critical role in promoting cancer by inhibiting cell death and encouraging tumor growth and spread.

Targeting and suppressing STAT3 activation can induce apoptosis in cancer cells, and various strategies, such as tyrosine kinase inhibitors and RNA interference, are being explored to develop effective cancer therapies that target this pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Siveen, KS., Sikka, S., Surana, R., et al.[2022]

In a study of 154 patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (SCC), high levels of activated STAT3 (pSTAT3) were linked to worse survival outcomes in SCC, while higher pSTAT3 levels in OAC were associated with better survival, indicating a complex role of STAT3 in different cancer types.

Treatment with the STAT3 inhibitor STATTIC in cancer cell lines led to reduced survival, proliferation, and migration, along with increased apoptosis, suggesting that targeting STAT3 could be a promising therapeutic strategy for both OAC and SCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. O' Sullivan, KE., Michielsen, AJ., O' Regan, E., et al.[2018]

Recent research has identified a variety of direct inhibitors targeting different domains of the STAT3 protein, which is crucial in cancer progression and migration, highlighting its potential as a therapeutic target.

Despite the promising development of 135 peer-reviewed studies and several patents for STAT3 inhibitors, no approved drugs currently exist for cancer treatment, indicating both the potential and challenges in targeting this pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents. Gelain, A., Mori, M., Meneghetti, F., et al.[2020]

STAT3 is a key player in many cancers, promoting tumor growth and survival, and its activation can be triggered by various signaling pathways, making it a critical target for cancer therapies.

Resistance to standard cancer treatments is often linked to persistent STAT3 activation, suggesting that combining these treatments with STAT3 inhibitors could improve patient outcomes, especially for cancer stem cells that are resistant to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of STAT3 signaling in mediating tumor resistance to cancer therapy. Tan, FH., Putoczki, TL., Stylli, SS., et al.[2019]

Chemoradiotherapy (CRT) is a common treatment for many cancers, but some tumors show resistance, leading to ineffective treatment and unnecessary side effects for patients.

Recent evidence suggests that the STAT3 protein is a key player in mediating resistance to CRT, and targeting STAT3 could be a promising strategy to enhance the effectiveness of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STAT3: A Novel Molecular Mediator of Resistance to Chemoradiotherapy. Spitzner, M., Ebner, R., Wolff, HA., et al.[2021]

Danvatirsen, an antisense oligonucleotide targeting STAT3, was found to be well tolerated in a Phase 1 study involving 11 Japanese patients with advanced solid tumors, with no new safety signals reported.

In combination with durvalumab, danvatirsen showed preliminary antitumor activity, with three patients achieving disease control at 12 weeks and one patient having an unconfirmed partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study. Nishina, T., Fujita, T., Yoshizuka, N., et al.[2022]

Stat3 plays a crucial role in tumor-associated inflammation by suppressing the Th1 immune response and promoting the growth of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, which can hinder effective anti-tumor immunity.

Targeting Stat3 with tyrosine kinase inhibitors or delivering Stat3 siRNA to immune cells may enhance cancer immunotherapy by reducing immunosuppression in the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STAT3: a target to enhance antitumor immune response. Lee, H., Pal, SK., Reckamp, K., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06098651

A Study of DCR-STAT3 in Adults With Solid Tumors

The DMC can recommend to the sponsor that the trial be stopped if it is not effective, is harming participants, or is unlikely to serve its scientific purpose.

2.

withpower.com

withpower.com/trial/phase-1-neoplasms-7-2023-2128e

DCR-STAT3 for Cancer · Info for Participants

The drug aims to block a protein that helps cancer grow, potentially shrinking the tumors or stopping their growth. Another compound, OPB-31121, is also being ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11898704/

Targeting STAT3 for Cancer Therapy: Focusing on Y705 ...

In this review, we evaluate the current STAT3 inhibitors and discuss the implications of targeting Y705, S727, or both residues for safe and effective cancer ...

4.

synapse.patsnap.com

synapse.patsnap.com/drug/a6bd82b47f8a4d95905e9eed4b225bfb

DCR-STAT3 - Drug Targets, Indications, Patents

An open-label, Phase 1, dose-ranging study to evaluate the safety, tolerability, and pharmacokinetics of intravenous DCR-STAT3 in adults with refractory solid ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2610472/

Targeting STAT3 in cancer: how successful are we? - PMC

This review is intended to be a full coverage of the efforts to develop direct STAT3 inhibitors and will provide a discussion on the inhibitory modalities ...

6.

frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1637958/full

analysis of clinical trial registration data from 2004 to 2024

Reflecting this, Novo Nordisk developed DCR-STAT3 to initiate a Phase I clinical trial (NCT06098651) in August 2023 to evaluate the safety, tolerability and ...