Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: DualityBio Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?A Phase 1/2a First-in-Human Study of DB-1419 in Advanced/Metastatic Solid Tumors
What safety data exists for DB-1419 in humans?
BBR 2778, which may be related to DB-1419, has been studied in humans and shows no significant heart-related side effects. However, it can cause low white blood cell counts (neutropenia), nausea, vomiting, and blue discoloration of skin and urine.
12345Will 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.
Eligibility Criteria
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
I am fully active or have some restrictions but can still care for myself.
My heart's pumping ability is normal, confirmed by a heart scan.
I understand the study's procedures and risks, can consent in writing, and will follow the study plan.
I am 18 years or older and can consent to treatment.
My cancer is advanced, cannot be surgically removed, and has not responded to or I have refused standard treatments.
Exclusion Criteria
I have previously been treated with B7-H3 targeted therapy.
I have a history of serious heart issues, including heart failure or arrhythmia.
I have or might have lung scarring or inflammation according to my medical records or recent scans.
I have a serious lung condition or need extra oxygen.
I have not needed IV treatment for an infection in the last 2 weeks.
Participant Groups
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.
14Treatment groups
Experimental Treatment
Group I: Dose Level 6Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 6
Group II: Dose Level 5Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 5
Group III: Dose Level 4Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 4
Group IV: Dose Level 3Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 3
Group V: Dose Level 2Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 2
Group VI: Dose Level 1Experimental Treatment1 Intervention
Enrolled subjects will receive DB-1419 at Dose Level 1
Group VII: Dose Expansion 8Experimental Treatment1 Intervention
Group VIII: Dose Expansion 7Experimental Treatment1 Intervention
Group IX: Dose Expansion 6Experimental Treatment1 Intervention
Group X: Dose Expansion 5Experimental Treatment1 Intervention
Group XI: Dose Expansion 4Experimental Treatment1 Intervention
Group XII: Dose Expansion 3Experimental Treatment1 Intervention
Group XIII: Dose Expansion 2Experimental Treatment1 Intervention
Group XIV: Dose Expansion 1Experimental Treatment1 Intervention
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Site USA08-0Newport Beach, CA
Site USA06-0Washington, D.C., United States
Site USA04-0Edison, NJ
Site USA07-0Nashville, TN
More Trial Locations
Loading ...
Who is running the clinical trial?
DualityBio Inc.Lead Sponsor
References
A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. [2019]The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was
A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. [2014]BBR 2778 is a novel aza-anthracenedione with no cardiotoxicity in preclinical models. This Phase I dose escalation trial of BBR 2778 was conducted to determine the maximum tolerated dose, the dose-limiting toxicity, and the pharmacokinetic profile of BBR 2778 in patients with advanced solid tumors. BBR 2778 was given in three consecutive weekly 30-min i.v. infusions over a 4-week cycle (cy). Thirty patients (pts) were treated with BBR 2778 at doses ranging from 5 to 150 mg/m2/week. The dose levels 5, 10, 16.5, 25, 37.5, 75, 112.5, and 150 mg/m2/week were investigated in 4 pts (9 cy), 3 pts (3 cy), 3 pts (5 cy), 6 pts (9 cy), 1 pt (1 cy), 4 pts (9 cy), 6 pts (18 cy), and 3 pts (4 cy), respectively. The dose-limiting toxicity was neutropenia, typically occurring at day 14. Other toxicities were mild to moderate and were principally thrombocytopenia, lymphopenia, alopecia, nausea, and vomiting and blue coloration of the skin and urine. No significant cardiac toxicity was observed. The plasma dose concentration curve fitted a biexponential profile, with a rapid distribution phase followed by a prolonged elimination phase (mean t1/2,z, 12 h). BBR 2778 displayed a large volume of distribution (range, 9.7-29.7 l/kg) with a high plasma clearance rate (0.75-1.31 l/h/kg). Less than 10% of the dose was recovered in urine as unchanged drug. The maximum tolerated dose was 150 mg/m2/week for 3 weeks, every 4 weeks. On the basis of this study, the recommended dose for Phase II studies is 112.5 mg/m2/week days 1 and 8 with individual optional administration at day 15, every 4 weeks. Antitumor activity was observed in patients with breast, small cell lung carcinoma, and facial cylindroma. This trial showed that BBR 2778 has a manageable toxicity profile on a weekly schedule. This lead compound of the aza-anthracenedione family shows promising antitumor activity and deserves Phase II investigation in patients with high risk of cumulative cardiotoxicity, such as anthracycline-pretreated breast cancer patients.
Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma. [2020]BBR 2778 is a novel aza-anthracenedione showing no cardiotoxicity and superior activity compared to doxorubicin and mitoxantrone in animal models. Objectives of this phase I study included the determination of the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), clinical pharmacokinetics (PK), and antitumor activity. Patients with relapsed or refractory, advanced non-Hodgkin's lymphoma were included.
Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas. [2014]BBR 2778 is a new aza-anthracenedione. Its activity against hematologic neoplasias in a mouse model is greater than that of doxorubicin or mitoxantrone. A phase-I study in patients with non-Hodgkin's lymphoma (NHL) showed that the drug has promising anti-tumor activity. Therefore, a phase-II study in patients with relapsed aggressive NHL was initiated.
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. [2021]Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL.