First-in-human Study of DB-1419 for Advanced/Metastatic Solid Tumors

Official title

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

Overview

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

Interventions

• Drug DB-1419
  Administered Injection of Vein (I.V.)

Primary outcome measures

• 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]
• 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]
• Phase 1a: Maximum Tolerated Dose (MTD) [Time frame: From first study treatment administration until the initiation of Phase1b/2a, approximately up to 12 months.]
• 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.]
• 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.]

Secondary outcome measures (11)

• Phase 1a: ORR determined from tumor assessments 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.]
• 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 [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]
• Phase 1/2a: OS [Time frame: 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 [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: AUC0-tau [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: AUCinf [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: Cmax [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: Tmax [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: Ctrough [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: ADA prevalence [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]
• Phase 1/2a: ADA incidence [Time frame: within 8 cycles (each cycle is 21 days or 14 days)]

Eligibility criteria

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 0-1.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 24 centers

• Site CHN24-0 — Hefei
• Site CHN39-0 — Hefei
• Site CHN28-0 — Beijing
• Site CHN13-0 — Jilin City
• Site CHN16-0 — Chongqing
• Site CHN20-0 — Fuzhou
• Site CHN32-0 — Nanning
• Site CHN08-0 — Harbin
• … and 16 more centers

United States · 9 centers

• Site USA12-0 — Los Angeles
• Site USA08-0 — Newport Beach
• Site USA06-0 — Washington D.C.
• Site USA02-0 — Florida City
• Site USA11-0 — Chicago
• Site USA03 — Huntersville
• Site USA05-0 — Philadelphia
• Site USA07-0 — Nashville
• … and 1 more center

Australia · 3 centers

• AUS03-0 — North Ryde
• AUS01-0 — Randwick
• AUS02-0 — Nedlands

Publications

• Li C, Yao J, Yang J, Zhang Y, Qiu Y, Zhu Z, Hua H. Preclinical Evaluation of DB-1419, a Novel Bifunctional and Bispecific Anti-B7-H3 x PD-L1 Antibody-Drug Conjugate. Clin Cancer Res. 2025 Aug 14;31(16):3581-3593. doi: 10.1158/1078-0432.CCR-25-0634. PMID 40499141

Identifiers

NCT: NCT06554795 · DB-1419-O-1001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗