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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- DualityBio Inc.
- Enrollment
- 360
- Locations
- 39
- Primary Endpoint
- Phase 1a: Maximum Tolerated Dose (MTD)
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults aged ≥ 18 years at the time of voluntarily signing informed consent.
- •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.
- •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.
- •Has a life expectancy of ≥ 3 months.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-
- •Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
- •Has adequate organ function within 7 days prior to the first dose of study treatment.
- •Has adequate treatment washout period prior to the first dose of study treatment.
- •Is willing to provide pre-existing resected tumor samples when available or undergo fresh tumor biopsy if feasible for the measurement of B7-H3 level and other biomarkers if no contraindication.
- •Note: there is no minimum B7-H3 expression level mandatory for entry into the study.
- •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.
- •Male and female participants of reproductive/childbearing potential must agree to avoid pregnancy during the study and for at least 4 months and 7 months after the last dose of study treatment, respectively.
- •Male participants must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study treatment administration. Female participants must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study treatment administration.
Exclusion Criteria
- •Prior treatment with B7-H3 targeted therapy or prior treatment with ADC containing a topoisomerase I inhibitor payload.
- •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 active viral hepatitis.
- •Is a lactating mother, or pregnant as confirmed by pregnancy tests performed within 7 days prior to enrollment.
- •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, and are on stable or decreasing doses of corticosteroids equivalent to ≤10 mg/day prednisone are eligible for study entry.
- •Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 5.0, Grade ≤ 1 or baseline.
- •Has a prior history of immune-related adverse event that required permanent immune checkpoint inhibitor discontinuation per NCCN guidelines.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Dose Expansion 3
Intervention: DB-1419 (Drug)
Dose Level 9
Enrolled subjects will receive DB-1419 at Dose Level 9
Intervention: DB-1419 (Drug)
Dose Level 8
Enrolled subjects will receive DB-1419 at Dose Level 8
Intervention: DB-1419 (Drug)
Dose Expansion 6
Intervention: DB-1419 (Drug)
Dose Expansion 1
Intervention: DB-1419 (Drug)
Dose Expansion 4
Intervention: DB-1419 (Drug)
Dose Expansion 5
Intervention: DB-1419 (Drug)
Dose Expansion 7
Intervention: DB-1419 (Drug)
Dose Level 7
Enrolled subjects will receive DB-1419 at Dose Level 7
Intervention: DB-1419 (Drug)
Dose Expansion 8
Intervention: DB-1419 (Drug)
Dose Level 5
Enrolled subjects will receive DB-1419 at Dose Level 5
Intervention: DB-1419 (Drug)
Dose Expansion 2
Intervention: DB-1419 (Drug)
Dose Level 1
Enrolled subjects will receive DB-1419 at Dose Level 1
Intervention: DB-1419 (Drug)
Dose Level 2
Enrolled subjects will receive DB-1419 at Dose Level 2
Intervention: DB-1419 (Drug)
Dose Level 3
Enrolled subjects will receive DB-1419 at Dose Level 3
Intervention: DB-1419 (Drug)
Dose Level 4
Enrolled subjects will receive DB-1419 at Dose Level 4
Intervention: DB-1419 (Drug)
Dose Level 6
Enrolled subjects will receive DB-1419 at Dose Level 6
Intervention: DB-1419 (Drug)
Outcomes
Primary Outcomes
Phase 1a: Maximum Tolerated Dose (MTD)
Time Frame: 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)
Time Frame: 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
Time Frame: 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 with best overall response of CR and PR
Phase 1/2a: Percentage of Participants with Adverse events (AE) serious AE (SAE)
Time Frame: Up to 90 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)
Time Frame: Up to 90 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
Secondary Outcomes
- Phase 1/2a: Cmax(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: Ctrough(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: Tmax(within 8 cycles (each cycle is 21 days or 14 days))
- 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.)
- Phase 1/2a: AUC0-last(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: AUCinf(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: ADA incidence(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: AUC0-tau(within 8 cycles (each cycle is 21 days or 14 days))
- Phase 1/2a: ADA prevalence(within 8 cycles (each cycle is 21 days or 14 days))
- 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)
- 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.)