DB-1419 for Advanced Cancer

Recruiting at 20 trial locations

Overseen By Milly Zang

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: DualityBio Inc.

Must not be taking: Corticosteroids, Anticonvulsants

Disqualifiers: Heart failure, Myocardial infarction, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 cycles (each cycle is 21 days or 14 days)

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called DB-1419 for individuals with advanced or metastatic solid tumors that have recurred or worsened after other treatments. The goal is to assess the safety and effectiveness of various doses. Participants will receive one of several doses of DB-1419 to determine the optimal dose. This trial suits those with solid tumors that cannot be surgically removed and have not responded to standard treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires an adequate treatment washout period (time without taking certain medications) before the first dose of the study treatment, so you may need to stop some of your current medications. It's best to discuss this with the trial team to understand which medications are affected.

Is there any evidence suggesting that DB-1419 is likely to be safe for humans?

Studies have shown that DB-1419 is generally safe in lab tests. It effectively targeted several types of tumors and demonstrated favorable pharmacokinetics, meaning it works well in the body. While promising, this trial is in the early stages, specifically Phase 1/2a. This phase primarily tests the treatment's safety in humans and how the body processes it. So far, evidence suggests DB-1419 is well-tolerated, but more data from human trials is needed to confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DB-1419 is unique because it offers a novel approach to treating advanced cancer by potentially targeting cancer cells more precisely than traditional chemotherapy. Unlike standard treatments that often affect both healthy and cancerous cells, DB-1419 may have a mechanism that allows for a more targeted attack on cancer cells, which could reduce side effects. Researchers are excited about DB-1419 because it might offer improved efficacy and safety, promising a better quality of life for patients.

What evidence suggests that this trial's treatment, DB-1419, could be effective for advanced cancer?

Research has shown that DB-1419, the investigational treatment in this trial, exhibits strong effects against tumors in early studies. It has proven effective against various tumor types, including lung cancer, due to its ability to specifically target and destroy cancer cells. In earlier tests, DB-1419 resulted in three complete recoveries and two partial recoveries in patients with advanced cancer. Patients generally tolerated the treatment well, indicating a good safety record. These encouraging results suggest that DB-1419 could be a useful option for treating advanced or metastatic solid tumors. ^{1 2 4 5 6}

Who Is on the Research Team?

Lily Hu

Principal Investigator

DualityBio Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic solid tumors that have worsened after standard treatments, or when no standard treatment exists. Participants must have a measurable lesion, be in good physical condition (ECOG score of 0-1), and expect to live at least three more months. They should not have had certain heart conditions, prior B7-H3 therapy, significant QTcF prolongation, active autoimmune diseases requiring recent treatment, HIV infection, symptomatic CNS metastases without stability post-treatment, severe lung diseases or infections needing IV drugs within the last two weeks.

Inclusion Criteria

Has a life expectancy of ≥ 3 months

Has adequate treatment washout period prior to the first dose of study treatment

I have at least one tumor that can be measured.

Exclusion Criteria

I had a heart attack or unstable chest pain in the last 6 months.

I have previously been treated with B7-H3 targeted therapy.

Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to > 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DB-1419 at various dose levels to assess safety, tolerability, and preliminary antitumor activity

8 cycles (each cycle is 21 days or 14 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• DB-1419

Trial Overview The study tests DB-1419's safety and effectiveness on various advanced/metastatic solid tumors. It's a first-in-human research divided into phases: Phase 1a/1b determines the safe dosage while Phase 2a assesses how well it works against specific tumor types.

How Is the Trial Designed?

Group I: Dose Level 6 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 6

Group II: Dose Level 5 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 5

Group III: Dose Level 4 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 4

Group IV: Dose Level 3 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 3

Group V: Dose Level 2 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 2

Group VI: Dose Level 1 Experimental Treatment 1 Intervention

Enrolled subjects will receive DB-1419 at Dose Level 1

Group VII: Dose Expansion 8 Experimental Treatment 1 Intervention

Group VIII: Dose Expansion 7 Experimental Treatment 1 Intervention

Group IX: Dose Expansion 6 Experimental Treatment 1 Intervention

Group X: Dose Expansion 5 Experimental Treatment 1 Intervention

Group XI: Dose Expansion 4 Experimental Treatment 1 Intervention

Group XII: Dose Expansion 3 Experimental Treatment 1 Intervention

Group XIII: Dose Expansion 2 Experimental Treatment 1 Intervention

Group XIV: Dose Expansion 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

DualityBio Inc.

Lead Sponsor

Trials

12

Recruited

5,800+

Published Research Related to This Trial

In a phase-II study involving 33 patients with relapsed aggressive non-Hodgkin's lymphoma (NHL), BBR 2778 demonstrated significant anti-tumor activity, achieving 5 complete and 4 partial remissions, with response durations lasting up to 17+ months.

The treatment was generally well tolerated, with neutropenia being the main side effect, suggesting that BBR 2778 could be a promising option for elderly patients who have already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas. Borchmann, P., Morschhauser, F., Parry, A., et al.[2014]

In a phase 2 trial involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), loncastuximab tesirine demonstrated a significant overall response rate of 48.3%, indicating its effectiveness as a treatment option for this challenging patient population.

The treatment was associated with an acceptable safety profile, with serious adverse events occurring in 39% of patients, but none were directly linked to loncastuximab tesirine, suggesting it may be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Caimi, PF., Ai, W., Alderuccio, JP., et al.[2021]

BBR 2778, an anthracenedione analogue, shows promise as an antitumor agent with reduced cardiotoxicity compared to similar drugs, as demonstrated in a phase I study involving 24 patients.

The study identified neutropenia as the dose-limiting toxicity at higher doses, while a significant reduction in tumor size was observed in a patient with small cell lung carcinoma, suggesting potential efficacy for further investigation at a recommended dose of 180 mg/m2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. Dawson, LK., Jodrell, DI., Bowman, A., et al.[2019]

BBR 2778, a new aza-anthracenedione, was found to have a maximum tolerated dose of 150 mg/m2/week with manageable toxicity, primarily neutropenia, and no significant cardiac toxicity, making it a safer option for patients with advanced solid tumors.

The drug demonstrated promising antitumor activity in patients with breast cancer, small cell lung carcinoma, and facial cylindroma, suggesting it could be particularly beneficial for those at risk of cardiotoxicity from other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. Faivre, S., Raymond, E., Boige, V., et al.[2014]

BBR 2778, a new aza-anthracenedione, was found to have a maximum tolerated dose of 84 mg/m2 with neutropenia identified as the dose-limiting toxicity in a phase I study involving 26 patients with advanced non-Hodgkin's lymphoma.

The drug demonstrated promising antitumor activity, achieving three complete remissions and two partial remissions, indicating its potential effectiveness in patients who have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma. Borchmann, P., Schnell, R., Knippertz, R., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40499141/

Preclinical Evaluation of DB-1419, a Novel Bifunctional ... Conclusions: DB-1419 demonstrated potent antitumor activity against multiple tumors, with favorable pharmacokinetic and safety profiles. These ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06554795

First-in-human Study of DB-1419 for Advanced/Metastatic ... Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor that has relapsed or progressed on or after standard systemic treatments ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/16/3581/763995/Preclinical-Evaluation-of-DB-1419-a-Novel

Preclinical Evaluation of DB-1419, a Novel Bifunctional and ... Besides, bystander-killing effects also contribute to the robust in vivo and in vitro antitumor effects of DB-1419 against lung cancer and beyond. In ...

4. clinrol.com clinrol.com/study/NCT06554795

DB-1419 for Advanced Solid Tumors First-in-human Phase 1/2a study evaluating safety, tolerability, and early antitumor activity of DB-1419 in advanced/metastatic solid tumors.

5. withpower.com withpower.com/trial/phase-2-solid-tumors-adult-7-2024-d3694

DB-1419 for Advanced Cancer The drug demonstrated promising antitumor activity, achieving three complete remissions and two partial remissions, indicating its potential effectiveness in ...

6. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT121/761593/Abstract-CT121-A-phase-1-2a-multicenter-open-label

Abstract CT121: A phase 1/2a, multicenter, open-label, first in ... Preclinical studies demonstrated that DB-1419 exhibited both direct cancer cell killing and immune-modulating functions. ... (DB-1419) in advanced ...