First-in-human Study of DB-1419 for Advanced/Metastatic Solid Tumors
- Registration Number
- NCT06554795
- Lead Sponsor
- DualityBio Inc.
- Brief Summary
A Phase 1/2a First-in-Human Study of DB-1419 in Advanced/Metastatic Solid Tumors
- Detailed Description
A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1419 in Participants with Advanced/Metastatic Solid Tumors
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 360
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Adults aged ≥ 18 years at the time of voluntarily signing informed consent.
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Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor that has relapsed or progressed on or after standard systemic treatments, or refused the standard treatment, or for which no standard treatment is available.
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At least one measurable lesion as assessed by the Investigator according to RECIST v1.1 criteria (Only applicable to backfill participants in phase 1a and participants in phase 1b/2a). CRPC participants with bone-only disease may be eligible on a case-by-case basis after discussion with the Medical Monitor.
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Has a life expectancy of ≥ 3 months.
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Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
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Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
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Has adequate organ function within 7 days prior to the first dose of study treatment.
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Has adequate treatment washout period prior to the first dose of study treatment.
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Is willing to provide pre-existing resected tumor samples when available or undergo fresh tumor biopsy if feasible for the measurement of B7-H3/PD-L1 level and other biomarkers if no contraindication.
Note: there is no minimum B7-H3/PD-L1 expression level mandatory for entry into the study.
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Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.
- Prior treatment with B7-H3 targeted therapy.
- Has a medical history of symptomatic congestive heart failure (New York Heart Association [NYHA] classes II-IV or serious cardiac arrhythmia requiring treatment.
- Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
- 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.
- Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis which needs glucocorticoids and antibiotics) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
- Has a history of underlying pulmonary disorder including, but not limited to, pulmonary emboli within 3 months of the start of study treatment, severe asthma, severe COPD, restrictive lung disease, and other clinically significant pulmonary compromise or requirement for supplemental oxygen.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
- Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals within 2 weeks before first dose of study treatment.
- Know human immunodeficiency virus (HIV) infection.
- Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with asymptomatic CNS metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed therapy (defined as 2 brain images, same imaging modality, both of which are obtained after treatment to the brain metastases; these imaging scans should be obtained at least 4 weeks apart and show no evidence of intracranial progression), and are on stable or decreasing doses of corticosteroids equivalent to ≤10 mg/day prednisone are eligible for study entry.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Level 5 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 5 Dose Expansion 2 DB-1419 - Dose Expansion 6 DB-1419 - Dose Expansion 5 DB-1419 - Dose Level 2 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 2 Dose Expansion 3 DB-1419 - Dose Expansion 8 DB-1419 - Dose Level 3 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 3 Dose Level 4 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 4 Dose Level 1 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 1 Dose Level 6 DB-1419 Enrolled subjects will receive DB-1419 at Dose Level 6 Dose Expansion 7 DB-1419 - Dose Expansion 1 DB-1419 - Dose Expansion 4 DB-1419 -
- Primary Outcome Measures
Name Time Method Phase 1/2a: Percentage of Participants with Adverse events (AE) serious AE (SAE) Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first Percentage of participants with TEAEs graded according to NCI CTCAE v5.0
Phase 1/2a: Percentage of Participants with serious AE (SAE) Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first Percentage of participants with SAEs graded according to NCI CTCAE v5.0
Phase 1a: Maximum Tolerated Dose (MTD) From first study treatment administration until the initiation of Phase1b/2a, approximately up to 12 months. MTD on the data collected during Part 1
Phase 1a: Recommended Phase 2 Dose (RP2D) From first study treatment administration until the initiation of Phase 1b/2a, approximately up to 12 months. RP2D of DB-1419 based on the data collected during Part 1
Phase 1b/2a: Objective Response Rate (ORR) determined by Investigator per RECIST v1.1 Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months. The percentage of subjects who had a best response rating of CR and PR
- Secondary Outcome Measures
Name Time Method Phase 1/2a: Tmax within 8 cycles (each cycle is 21 days or 14 days) Time to Cmax
Phase 1/2a: Cmax within 8 cycles (each cycle is 21 days or 14 days) peak observed concentration
Phase 1/2a: Ctrough within 8 cycles (each cycle is 21 days or 14 days) trough concentration
Phase 1/2a: OS From the start date of study drug to the date of death due to any cause, whichever occurs first, approximately up to 12 months after last patient first dose. overall survival (OS)
Phase 1/2a: AUC0-last within 8 cycles (each cycle is 21 days or 14 days) the area under the concentration-time curve from time zero to the last quantifiable concentration
Phase 1a: ORR determined from tumor assessments by Investigator per RECIST v1.1 Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months. The percentage of subjects who had a best response rating of CR and PR
Phase 1/2a: AUC0-tau within 8 cycles (each cycle is 21 days or 14 days) the area under the concentration-time curve from time zero to time tau
Phase 1/2a: ADA prevalence within 8 cycles (each cycle is 21 days or 14 days) the proportion of participants who are ADA positive at any point in time (at baseline and post-baseline)
Phase 1/2a: Progression free survival (PFS) determined from tumor assessments by Investigator per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1 Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months PFS will be determined from tumor assessments by investigator per RECIST 1.1
Phase 1/2a: AUCinf within 8 cycles (each cycle is 21 days or 14 days) the area under the concentration-time curve from time zero to infinite
Phase 1/2a: ADA incidence within 8 cycles (each cycle is 21 days or 14 days) the proportion of participants having treatment-emergent ADA.
Trial Locations
- Locations (17)
Site USA08-0
🇺🇸Newport Beach, California, United States
Site USA06-0
🇺🇸Washington, D.C., District of Columbia, United States
Site USA02
🇺🇸Florida City, Florida, United States
Site USA04-0
🇺🇸Edison, New Jersey, United States
Site USA03
🇺🇸Carolina, North Carolina, United States
Site USA05-0
🇺🇸Philadelphia, Pennsylvania, United States
Site USA07-0
🇺🇸Nashville, Tennessee, United States
AUS03-0
🇦🇺North Ryde, New South Wales, Australia
AUS01-0
🇦🇺Randwick, New South Wales, Australia
AUS02-0
🇦🇺Nedlands, Western Australia, Australia
Site CHN08-0
🇨🇳Ha'erbin, Heilongjiang, China
Site CHN03-0
🇨🇳Luoyang, Henan, China
Site CHN06-0
🇨🇳Shanghai, Shanghai, China
Site CHN13-0
🇨🇳Changchun, China
Site CHN01-0
🇨🇳Shanghai, China
Site CHN05-0
🇨🇳Shanghai, China
Site CHN09-0
🇨🇳Zhengzhou, China