DZ-002 for Cancer

Overseen By Robert L De Jager, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Da Zen Theranostics Inc

Must not be taking: Simvastatin, Antiarrhythmics, CYP3A4 inhibitors

Disqualifiers: Cardiac disease, Infections, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called DZ-002, a potential drug for individuals with advanced solid tumors, including certain cancers unresponsive to standard treatments. The main focus is to assess the treatment's safety and determine the right dose for future studies. Individuals with solid tumors that cannot be removed or have spread, and who have not succeeded with other treatments, might be suitable for this trial. 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 it.

Do I have to stop taking my current medications for the trial?

The trial requires stopping certain medications. You must stop taking simvastatin and any strong inhibitors or inducers of CYP3A4, CYP2B6, CYP1A2, CYP2C9, and CYP2C8 before and during the study. If you're on these, discuss with your doctor.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as simvastatin and strong inhibitors or inducers of specific enzymes (CYP3A4, CYP2B6, CYP1A2, CYP2C9, and CYP2C8), before and during the study. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that DZ-002 is likely to be safe for humans?

Research has shown that DZ-002 aims to enhance existing cancer treatments by directly targeting cancer cells. This approach could lead to more effective treatment with fewer side effects. However, specific safety information for DZ-002 is not yet available.

As a Phase 1 trial, the primary goal is to assess the safety of DZ-002 in humans and determine the optimal dose. This indicates that the treatment has not been tested on many people yet. Phase 1 trials typically involve small groups to identify any side effects and evaluate how well participants tolerate the treatment. DZ-002 has progressed to Phase 2 trials, suggesting it was well-tolerated in earlier studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DZ-002 is unique because it offers a fresh approach to cancer treatment by being administered once weekly, which could potentially improve patient convenience and adherence compared to more frequent dosing schedules. Researchers are excited about DZ-002 because it may work differently than standard chemotherapy and targeted therapies by specifically targeting cancer cells with minimal impact on healthy cells, potentially leading to fewer side effects. This novel mechanism of action could offer a promising alternative for patients who have not responded well to existing treatments.

What evidence suggests that DZ-002 might be an effective treatment for cancer?

Research shows that DZ-002 aims to enhance existing cancer treatments by delivering them directly into cancer cells. This targeted method may boost treatment effectiveness while reducing side effects. Early results suggest that DZ-002 could improve outcomes for patients with solid tumors, especially those unresponsive to standard treatments. Although limited information from human studies exists, the drug's new delivery method appears promising in enhancing cancer drugs. More studies are needed to confirm its efficacy and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Robert L De Jager, MD

Principal Investigator

Dazen Theranostics

Are You a Good Fit for This Trial?

Adults with advanced solid tumors or lymphoma that haven't responded to standard treatments can join this trial. They must be able to follow the study plan, have a life expectancy over 8 weeks, and good organ function. Women of childbearing age need a negative pregnancy test and agree to use birth control.

Inclusion Criteria

Adequate bone marrow, liver, and renal function as defined below: Hemoglobin ≥ 8.0 g/dL, Absolute neutrophil count ≥ 1500/μL, Platelet count ≥ 75,000/ μL, Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of normal (ULN) or ≤ 5 × ULN for patients with known hepatic metastases, Total serum bilirubin ≤ 1.5× ULN or ≤ 2 .0 × ULN if liver metastases are present, Estimated creatinine clearance ≥ 40 mL/min, Adequate cardiac function as estimated by left ventricular ejection fraction (LVEF) > 50% by multiple-gated acquisition (MUGA) or echocardiogram (ECHO), Negative pregnancy test for women of childbearing potential

Written informed consent from the patient or the patient's legally acceptable representative prior to the initiation of any study procedures

My cancer is advanced, cannot be surgically removed, and hasn't responded to standard treatments.

Exclusion Criteria

New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, a history of risk factors for Torsades de Pointes, active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy, treatment with simvastatin unless it can be stopped prior to and during the study, treatment with strong inhibitors and inducers of CYP3A4 or narrow therapeutic index substrates of CY3A4, CYP2B6, CYP1A2, CYP2C9 and CYP2C8, known sensitivity to DZ-002 or drug excipients, pregnant or breast feeding, treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 30 days prior to study entry, unwillingness or inability to comply with procedures required in this protocol, known infection with human immunodeficiency virus and CD4 lymphocyte count < 200 cells/mm3, or active hepatitis B virus, or hepatitis C virus infections, serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor, patients who are currently receiving any other investigational agent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of DZ-002 in patients with advanced cancers

28-day cycles

Weekly visits for IV infusion on days 1, 8, 15, and 22

Dose Expansion

Investigate the MTD and/or RP2D in two expansion treatment groups: castration-resistant prostate cancer and advanced pancreatic cancer

28-day cycles

Weekly visits for IV infusion on days 1, 8, 15, and 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• DZ-002

Trial Overview The study is testing DZ-002's safety and finding the highest dose patients can take without serious side effects (MTD). It also aims to find the best dose for future studies (RP2D) while checking how the body processes it and its effectiveness against tumors.

How Is the Trial Designed?

Group I: Dose escalation and cohort expansion Q1W Experimental Treatment 1 Intervention

DZ-002 treatment once every week

Who Is Running the Clinical Trial?

Da Zen Theranostics Inc

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

In a phase 1b study involving 27 patients with non-small cell lung cancer (NSCLC), the combination of atezolizumab and ipilimumab showed promising efficacy, with 26% of patients achieving confirmed responses, particularly among those who had not previously received checkpoint inhibitors.

The treatment was found to have a manageable safety profile, with no dose-limiting toxicities reported and common adverse events including dyspnea and cough, indicating that the combination therapy is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Ipilimumab in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Results From a Phase 1b Trial. Wong, DJ., Bauer, TM., Gordon, MS., et al.[2022]

This study evaluated two innovative methods, OncoTarget and OncoTreat, to predict how tumors respond to various cancer drugs in patients with difficult-to-treat malignancies, achieving significant disease control rates of 68% and 91%, respectively.

The predicted drugs not only performed better than standard treatments but also successfully altered the activity of key regulatory proteins in tumors, suggesting these methods could enhance precision medicine strategies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies. Mundi, PS., Dela Cruz, FS., Grunn, A., et al.[2023]

A meta-analysis of nine randomized controlled trials showed that PD-1 inhibitors significantly increase the risk of developing all-grade hepatic adverse events (AEs) in cancer patients, although high-grade AEs were not significantly affected compared to chemotherapy or everolimus.

The combination of nivolumab and ipilimumab resulted in a notably higher risk of all-grade and high-grade hepatic AEs compared to ipilimumab alone, indicating that while PD-1 inhibitors can be effective, they also carry a risk of liver-related side effects, primarily of lower severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk of hepatic toxicities with PD-1 inhibitors in cancer patients: a meta-analysis. Zhang, X., Ran, Y., Wang, K., et al.[2018]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

A study identified 131 genes that are significantly dysregulated in platinum-resistant ovarian cancer tissues compared to sensitive ones, with 30 of these genes linked to disease-free survival (DFS) and overall survival (OS) in a cohort of 489 patients.

Among these, PDIA4 was found to be a key predictor of both DFS and OS, and its downregulation was confirmed in patient specimens, suggesting it could serve as a potential therapeutic target or biomarker for ovarian cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microarray-based identification of genes associated with prognosis and drug resistance in ovarian cancer. Yin, F., Yi, S., Wei, L., et al.[2020]

Temozolomide (TMZ) and the checkpoint kinase inhibitor AZD7762 both showed time- and concentration-dependent cytotoxic effects on human glioma cells, with their combination resulting in synergistic effects that enhance cell death.

The combination treatment of TMZ and AZD7762 not only suppressed the expression of the DNA repair protein MGMT but also modulated several signaling pathways, suggesting a complex mechanism that may improve the efficacy of glioma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and AZD7762 Induce Synergistic Cytotoxicity Effects on Human Glioma Cells. Chen, Y., Tseng, BJ., Tsai, YH., et al.[2022]

Five patient-derived xenograft (PDX) models of HER2-positive gastric cancer were successfully established, reflecting the HER2 expression of actual patient tumors, which is crucial for developing targeted therapies.

Testing these PDX models showed that a novel HER2 antibody combined with Herceptin significantly improved anti-cancer efficacy, indicating potential for enhanced treatment strategies in HER2-positive gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of a Patient-derived Xenograft for Development of Personalized HER2-targeting Therapy in Gastric Cancer. Shin, SH., Park, SS., Ju, EJ., et al.[2018]

A total of 127 patient-derived tumor xenografts (PDXs) were successfully established from 441 non-small cell lung cancer (NSCLC) samples, representing various tumor subtypes, which closely mimic the characteristics of human tumors.

The PDX models exhibited greater genetic and proteomic similarity to patient tumors compared to traditional cell lines, allowing for the identification of novel mutations that may be missed in standard models, thus enhancing the potential for personalized cancer research and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular heterogeneity of non-small cell lung carcinoma patient-derived xenografts closely reflect their primary tumors. Wang, D., Pham, NA., Tong, J., et al.[2022]

High expression levels of PD-L2 in lower-grade gliomas (LGGs) are associated with a worse prognosis and can serve as an independent prognostic factor for survival, as shown through Cox regression analysis of patient data.

PD-L2 expression correlates with immune infiltration and predicts sensitivity to both immunotherapy and TMZ-based chemotherapy, suggesting it could guide personalized treatment strategies for LGG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L2 Serves as a Potential Prognostic Biomarker That Correlates With Immune Infiltration and May Predict Therapeutic Sensitivity in Lower-Grade Gliomas. Xie, Q., Huang, X., Huang, W., et al.[2022]

In a mouse model of glioma, combining temozolomide (TMZ) with anti-PD-1 antibody therapy significantly improved overall survival compared to either treatment alone, indicating a potential synergistic effect.

The combination therapy also resulted in a notable reduction in tumor size and an increase in the infiltration of immune cells (CD4 and CD8 T cells) within the tumor, suggesting enhanced immune response against the glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide combined with PD-1 Antibody therapy for mouse orthotopic glioma model. Dai, B., Qi, N., Li, J., et al.[2018]

Prolonged exposure to GZ17-6.02 significantly enhanced the effectiveness of both 5-fluorouracil and an anti-PD1 antibody in treating colorectal tumors, leading to longer survival in animal models.

Resistance mechanisms in tumor cells exposed to GZ17-6.02 were identified, including increased expression of certain receptors and proteins, but this resistance could be partially reversed by using HDAC inhibitors, restoring the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of GZ17-6.02 resistance. Booth, L., West, C., Von Hoff, D., et al.[2023]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

In a study involving 1738 patients with advanced solid tumors treated with avelumab, a PD-L1 antibody, only 10.2% experienced grade ≥3 treatment-related adverse events (TRAEs), indicating a generally well-tolerated safety profile.

Infusion-related reactions (IRRs) were common, occurring in 25.3% of patients, primarily at the first infusion, but serious IRRs (grade ≥3) were rare, suggesting that while some patients may experience reactions, they are typically manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. Kelly, K., Infante, JR., Taylor, MH., et al.[2020]

In a study of 63 ovarian clear cell carcinoma (OCCC) patients, HER2 and AURKA expression levels were associated with shorter progression-free and overall survival times, indicating their potential as prognostic factors.

Despite the associations found, none of the six biomarkers studied (including EGFR, HER2, AURKA, BRCA1, BRCA2, and PD-L1) were identified as independent risk factors for survival outcomes, suggesting that while they may indicate prognosis, they do not independently predict patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma]. Li, MJ., Li, HR., Cheng, X., et al.[2019]

Temozolomide (tmz) is commonly used in Canadian children with brain tumors, particularly at the time of tumor recurrence, with 137 children treated across 10 pediatric oncology centers from 2000 to 2006.

While some patients showed positive responses to tmz, including complete and partial responses, the overall effectiveness and clear indications for its use in pediatric brain tumors remain uncertain due to a lack of well-designed clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and effectiveness of temozolomide in children with central nervous system tumours: a survey from the Canadian Paediatric Brain Tumour Consortium. Bartels, U., Baruchel, S., Carret, AS., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04970992

Study Details | NCT04970992 | A Pharmacokinetic and ... The study will be conducted in 2 phases, a dose escalation phase and a dose expansion phase. The dose-escalation phase will first determine the MTD and/or RP2D ...

2. provost.gsu.edu provost.gsu.edu/2024/12/18/cancer-treatment-dazen-theranostics/

Novel Cancer Treatment From Georgia State Research ... “DZ improves existing cancer drugs by transporting them directly into cancer cells, resulting in greater efficacy and fewer side effects.” The ...

3. withpower.com withpower.com/trial/phase-1-lymphoma-7-2021-3eb6b

DZ-002 for Cancer · Info for Participants This trial tests DZ-002, a new drug for cancer patients whose standard treatments didn't work. It involves regular IV doses to check safety, body behavior, and ...

4. saportareport.com saportareport.com/breakthrough-cancer-therapy-moves-to-phase-2-trials/thought-leadership/higher-education/georgia-state-university/

Breakthrough Cancer Therapy Moves to Phase 2 Trials DZ-002 is an innovative cancer treatment developed through a collaborative effort among Georgia State University, Emory University and Cedars- ...

5. trialx.com trialx.com/clinical-trials/listings/243480/a-pharmacokinetic-and-pharmacodynamic-study-of-dz-002-in-patients-with-advanced-solid-malignancies-or-lymphoma/

A Pharmacokinetic and Pharmacodynamic Study of DZ ... The study will be conducted in 2 phases, a dose escalation phase and a dose expansion phase. The dose-escalation phase will first determine the ...

6. bioengineer.org bioengineer.org/groundbreaking-cancer-therapy-advances-to-phase-2-trials/

Groundbreaking Cancer Therapy Advances to Phase 2 Trials : Breakthrough Cancer Therapy DZ-002 Advances into Phase 2 Trials, Offering Hope for Pancreatic Cancer Patients. News Publication Date ...