32 Participants Needed

DCR-PDL1 for Cancer

Recruiting at 1 trial location
VU
NN
Overseen ByNovo Nordisk
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DCR-PDL1 to assess its safety and behavior in the body. It targets adults with solid tumors or non-Hodgkin's lymphoma that have not responded to standard treatments or for whom no standard treatments exist. Participants will receive the medication through a series of IV doses, with each group trying a different dose level to determine the safest and most effective amount. This trial may suit those whose cancer has worsened despite treatment or cannot be treated with surgery. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that DCR-PDL1 is likely to be safe for humans?

Research shows that treatments targeting PD-L1, such as DCR-PDL1, are usually well-tolerated. Studies with similar PD-1 and PD-L1 inhibitors have reported few side effects, with serious side effects being rare. While these treatments are mostly safe, some patients might still experience mild side effects, including tiredness, skin reactions, or flu-like symptoms. When used for other conditions, these treatments generally support their safety for new uses. Always consult a doctor about specific risks and benefits before joining a trial.12345

Why do researchers think this study treatment might be promising?

Most treatments for cancer focus on targeting tumor cells directly or boosting the immune system to attack them. DCR-PDL1 is unique because it uses an innovative mechanism to silence the PD-L1 protein, which often helps cancer cells evade the immune system. By targeting PD-L1, this treatment could potentially enhance the body's natural ability to fight cancer more effectively than existing immunotherapies. Researchers are excited about DCR-PDL1 because this approach might offer a new way to overcome resistance seen with current therapies, potentially leading to better outcomes for patients.

What evidence suggests that DCR-PDL1 might be an effective treatment for cancer?

Research has shown that PD-1 and PD-L1 inhibitors hold promise in cancer treatment. These treatments can extend the time patients live without their cancer worsening. For instance, patients using similar PD-1 inhibitors lived about 11.5 months without cancer progression, compared to just 2.9 months for those not using these inhibitors. Additionally, about 23-28% of patients experienced a partial or full reduction in tumor size with these treatments. This trial will evaluate DCR-PDL1, which functions similarly, to assess its potential effectiveness in treating solid tumors.12678

Who Is on the Research Team?

CT

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors. Participants will be placed into one of four groups to receive increasing doses of DCR-PDL1, given through the veins. Specific eligibility details are not provided, but typically include factors like type and stage of tumor, previous treatments, and overall health.

Inclusion Criteria

My cancer is advanced, not responding to standard treatments, or there are no treatments available.
Measurable disease according to RECIST version 1.1
Other protocol defined inclusion criteria could apply
See 2 more

Exclusion Criteria

Other protocol defined exclusion criteria could apply
I have brain or spinal cord metastases not managed by surgery or radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple IV doses of DCR-PDL1 during each treatment cycle in one of 4 ascending-dose cohorts

8 weeks
Multiple visits for IV dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • DCR-PDL1
Trial Overview The study tests the safety and how well the body handles DCR-PDL1 when administered intravenously in adults with solid tumors. It involves multiple IV doses within treatment cycles, with close monitoring to decide if higher doses can be safely given.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: DCR-PDL1Experimental Treatment1 Intervention

Find a Clinic Near You

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

In a systematic review of 125 clinical trials involving over 20,000 patients, 66% experienced at least one treatment-related adverse event from PD-1 and PD-L1 inhibitors, with fatigue, pruritus, and diarrhea being the most common.
Nivolumab was found to have a higher incidence of adverse events compared to pembrolizumab, and PD-1 inhibitors generally led to more severe adverse events than PD-L1 inhibitors, highlighting the importance of understanding these differences for clinical decision-making.
Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis.Wang, Y., Zhou, S., Yang, F., et al.[2022]
Genetically modifying T cells to express a PD1-CD28-4-1BB receptor (PD1-ACR) enhances their ability to overcome PDL1-mediated immunosuppression, leading to improved T cell activation and function.
In a mouse model of glioblastoma, PD1-ACR T cells effectively localized to tumors, suppressed tumor growth, and improved survival rates, suggesting a promising new approach for cancer therapy.
The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy.Tang, X., Li, Q., Zhu, Y., et al.[2020]
In a study of 158 advanced biliary tract cancer patients, higher levels of soluble PD-L1 (sPDL1) in serum were associated with significantly worse overall survival, indicating its potential as a prognostic biomarker.
Patients with sPDL1 levels of 0.94 ng/mL or higher had a median overall survival of 7.93 months compared to 14.10 months for those with lower levels, highlighting sPDL1 as an independent poor prognostic factor alongside the neutrophil-to-lymphocyte ratio.
Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy.Ha, H., Nam, AR., Bang, JH., et al.[2022]

Citations

Effectiveness and safety of PD-1/PD-L1 inhibitors in the ...In one of the trials [31], the median PFS of patients treated with PD-1 inhibitor was 11.5 months, while it was only 2.9 months for those treated without PD-1 ...
Safety, Tolerability, and Pharmacokinetics of DCR-PDL1 in ...Study Details | NCT06504368 | Safety, Tolerability, and Pharmacokinetics of DCR-PDL1 in Adults With Solid Tumors | ClinicalTrials.gov.
Effectiveness and safety of PD-1/L1 inhibitors as first-line ...Our results revealed that PD-1/L1 inhibitors had certain therapeutic advantage, with ORR of 28% and DCR of 57%. Besides, the median PFS and OS ...
Efficacy of PD-1 or PD-L1 inhibitors for the therapy of cervical ...For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80–7.16, P = 0.01) and 11.26 months (95% CI: 3.01 ...
Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment ...The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, ...
Safety and Clinical Activity of a New Anti-PD-L1 Antibody as ...Clinical efficacy and antitumor activity endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), PFS, and OS.
Efficacy and safety of anti-PD-1 inhibitor versus ... - BMC CancerAnti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.
Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune ...A recent study showed that 100% of 12 patients with advanced dMMR rectal cancer achieved a complete clinical and pathological response after six months of ...
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