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

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

A Phase 1/2a First-in-Human Study of DB-1419 in Advanced/Metastatic Solid Tumors

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: DB-1419

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 Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Milly Zang; Phone Number: 858-375-6788; Email: milly.zang@dualitybiologics.com
• Study Contact Backup: Name: Cathy Li; Phone Number: 858-375-6788; Email: cathy.li@dualitybiologics.com

Study Locations

• Australia
  • New South Wales
    • North Ryde, New South Wales, Australia, 2109
      • Recruiting
      • AUS03-0
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • AUS01-0
  • Washington
    • Nedlands, Washington, Australia, 6009
      • Recruiting
      • AUS02-0
      • Contact: Email: cancertrialsonc3@linear.org.au
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Not yet recruiting
      • Site CHN24-0
    • Hefei, Anhui, China, 230031
      • Not yet recruiting
      • Site CHN39-0
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Not yet recruiting
      • Site CHN28-0
  • Changchun
    • Jilin, Changchun, China, 130000
      • Not yet recruiting
      • Site CHN13-0
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Recruiting
      • Site CHN16-0
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Site CHN20-0
  • Guangxi
    • Nanning, Guangxi, China, 530012
      • Not yet recruiting
      • Site CHN32-0
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • Site CHN08-0
    • Harbin, Heilongjiang, China, 150001
      • Not yet recruiting
      • Site CHN23-0
  • Henan
    • Luoyang, Henan, China, 471000
      • Recruiting
      • Site CHN03-0
    • Zhengzhou, Henan, China, 450000
      • Not yet recruiting
      • Site CHN09-0
    • Zhengzhou, Henan, China, 451191
      • Not yet recruiting
      • Site CHN25-0
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Site CHN34-0
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Site CHN21-0
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Not yet recruiting
      • Site CHN31-0
  • Shandong
    • Jinan, Shandong, China, 250117
      • Not yet recruiting
      • Site CHN29-0
    • Linyi, Shandong, China, 276034
      • Recruiting
      • Site CHN26-0
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Site CHN01-0
    • Shanghai, Shanghai Municipality, China, 200030
      • Recruiting
      • Site CHN15-0
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Site CHN18-0
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300000
      • Not yet recruiting
      • Site CHN38-0
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Not yet recruiting
      • Site CHN19-0
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Not yet recruiting
      • Site CHN17-0
    • Hangzhou, Zhejiang, China, 310009
      • Not yet recruiting
      • Site CHN37-0
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Site USA12-0
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Site USA08-0
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • Site USA06-0
  • Florida
    • Florida City, Florida, United States, 32827
      • Recruiting
      • Site USA02-0
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Site USA11-0
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Site USA03
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Not yet recruiting
      • Site USA05-0
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Site USA07-0
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • Site USA09-0

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged ≥ 18 years at the time of voluntarily signing informed consent.
2. 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.
3. 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.
4. Has a life expectancy of ≥ 3 months.
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
6. Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
7. Has adequate organ function within 7 days prior to the first dose of study treatment.
8. Has adequate treatment washout period prior to the first dose of study treatment.

9. 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.

10. 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.
11. 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.
12. 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:

1. Prior treatment with B7-H3 targeted therapy or prior treatment with ADC containing a topoisomerase I inhibitor payload.
2. Has a medical history of symptomatic congestive heart failure (New York Heart Association [NYHA] classes II-IV or serious cardiac arrhythmia requiring treatment.
3. Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
4. 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.
5. 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.
6. 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.
7. 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.
8. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals within 2 weeks before first dose of study treatment.
9. Know human immunodeficiency virus (HIV) infection.
10. Has active viral hepatitis.
11. Is a lactating mother, or pregnant as confirmed by pregnancy tests performed within 7 days prior to enrollment.
12. 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.
13. 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.
14. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Enrolled subjects will receive DB-1419 at Dose Level 1	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 2; Enrolled subjects will receive DB-1419 at Dose Level 2	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 3; Enrolled subjects will receive DB-1419 at Dose Level 3	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 4; Enrolled subjects will receive DB-1419 at Dose Level 4	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 5; Enrolled subjects will receive DB-1419 at Dose Level 5	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 6; Enrolled subjects will receive DB-1419 at Dose Level 6	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 1	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 2	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 3	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 4	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 5	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 6	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 7	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Expansion 8	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 7; Enrolled subjects will receive DB-1419 at Dose Level 7	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 8; Enrolled subjects will receive DB-1419 at Dose Level 8	Drug: DB-1419; Administered Injection of Vein (I.V.)
Experimental: Dose Level 9; Enrolled subjects will receive DB-1419 at Dose Level 9	Drug: DB-1419; Administered Injection of Vein (I.V.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Maximum Tolerated Dose (MTD)	MTD on the data collected during Part 1	From first study treatment administration until the initiation of Phase1b/2a, approximately up to 12 months.
Phase 1a: Recommended Phase 2 Dose (RP2D)	RP2D of DB-1419 based on the data collected during Part 1	From first study treatment administration until the initiation of Phase 1b/2a, approximately up to 12 months.
Phase 1/2a: Percentage of Participants with Adverse events (AE) serious AE (SAE)	Percentage of participants with TEAEs graded according to NCI CTCAE v5.0	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)	Percentage of participants with SAEs graded according to NCI CTCAE v5.0	Up to 90 days after last study treatment administration or before starting new anticancer treatment, whichever comes first
Phase 1b/2a: Objective Response Rate (ORR) determined by Investigator per RECIST v1.1	The percentage of subjects with best overall response of CR and PR	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

Outcome Measure	Measure Description	Time Frame
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	PFS will be determined from tumor assessments by investigator per RECIST 1.1	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 1/2a: OS	overall survival (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	the area under the concentration-time curve from time zero to the last quantifiable concentration	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: AUC0-tau	the area under the concentration-time curve from time zero to time tau	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: AUCinf	the area under the concentration-time curve from time zero to infinite	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: Cmax	peak observed concentration	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: Tmax	Time to Cmax	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: Ctrough	trough concentration	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: ADA prevalence	the proportion of participants who are ADA positive at any point in time (at baseline and post-baseline)	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1/2a: ADA incidence	the proportion of participants having treatment-emergent ADA.	within 8 cycles (each cycle is 21 days or 14 days)
Phase 1a: ORR determined from tumor assessments by Investigator per RECIST v1.1	The percentage of subjects with best overall response of CR and PR	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.

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Investigators: Study Director: Lily Hu, DualityBio Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: DB-1419-O-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No