A Study of DB-1310 in Advanced/Metastatic Solid Tumors

Advanced Solid Tumor Clinical Trial

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-1310 in Subjects With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05785741
• Other study ID #: DB-1310-O-1001
• Secondary ID: CTR20231736
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 10, 2023
• Est. completion date: August 31, 2026

Study information

• Verified date: August 2023
• Source: DualityBio Inc.
• Contact: Jenny Li
• Phone: +1-650-237-9339
• Email: jenny.li[@]dualitybiologics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1310 in subjects with advanced solid tumors.

Description:

This is a multicenter, non-randomized, open-label, multiple-dose, FIH Phase 1/2a study. Phase 1 adopts the standard "3+3" design to identify the MTD and/or RP2D; Phase 2a is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors treated with DB-1310 as monotherapy or in combination with trastuzumab.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 287
• Est. completion date: August 31, 2026
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female adults (defined as = 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).

2. Have relapsed or progressed on or after standard systemic treatments, or intolerable with standard treatment, or for which no standard treatment is available. Documented radiological disease progression during/after most recent treatment regimen for advanced/unresectable, or metastatic disease.

3. At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria. Subjects with nonmeasurable disease only are allowed in Cohort 2c of Phase 2a.

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 functions within 7 days prior to Day 1 of Cycle 1.

8. Has adequate treatment washout period prior to Day 1 of Cycle 1.

9. Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of HER3 level and other biomarkers if no contraindication.

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 subjects of reproductive/childbearing potential must agree to use adequate contraceptive methods (e.g., double barrier or intrauterine contraceptive) during the study and for at least 4 months and 7 months after the last dose of study drug, respectively.

12. Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration.

13. Female subjects 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 drug administration.

Exclusion Criteria:

1. Prior treatment with HER3 targeted therapy.

2. Prior treatment with antibody drug conjugate with topoisomerase I inhibitor (exclusive of trastuzumab deruxtecan for Cohort 2e of Phase 2a).

3. Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.

4. Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.

5. Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval > 250 milliseconds (ms).

6. 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.

7. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT interval.

8. Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.

9. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.

10. Has clinically significant corneal disease.

11. Know human immunodeficiency virus (HIV) infection.

12. Subjects have active viral (any etiology) hepatitis are excluded. However, subjects with positive hepatitis B surface antigen (HBsAg) who have the HBV DNA (viral load) below the lower limit quantification or HBV DNA titer < 1000 cps/mL or 200 IU/mL per local testing and are not currently on viral suppressive therapy may be eligible and should be discussed with the Sponsor's Medical Monitor. However, subjects with a history of hepatitis C virus (HCV) infection who have completed curative antiviral treatment and have the HCV RNA below the lower limit of quantification per local testing are eligible for study entry.

13. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by serum pregnancy tests performed within 7 days prior to Cycle 1 Day 1.

14. Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. However, subjects with asymptomatic central nervous system (CNS) metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed therapy, and who 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• DB-1310
Administered I.V.

Locations

Country	Name	City	State
China	The first hospital of Jilin University	Changchun	Jilin
China	Hunan cancer hospital	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chendu	Sichuan
China	Jiangsu Province hospital	Nanjing	Jiangsu
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Affiliated Hospital of Jiangnan University	Wuxi	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Carl & Edyth Lindner Center for Research & Education at The Christ Hospital and The Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	NEXT Virginia	Fairfax	Virginia
United States	D&H Cancer Research Center LLC	Margate	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida
United States	BRCR global	Plantation	Florida
United States	University of California, Davis Comprehensive Cancer Center	Sacramento	California
United States	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	BRCR Medical Center Inc.	Tamarac	Florida

Sponsors (1)

Lead Sponsor	Collaborator
DualityBio Inc.

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. Percentage of participants in Part 1 with DLTs	Percentage of participants in Part 1 with DLTs	up to 21 days after Cycle 1 Day 1
Primary	Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.	Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0assessed by CTCAE v5.0.; Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Primary	Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.	Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Primary	Maximum Tolerated Dose (MTD) of DB-1310	MTD on the data collected during Part 1	12 months
Primary	Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1310	RP2D of DB-1310 based on the data collected during Part 1	12 months
Primary	Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.	Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Primary	Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.	Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Primary	Phase 2a: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.	The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained =4 weeks	Up to follow-up period, approximately 1 year post-treatment
Secondary	Phase 1 & Phase 2a: Pharmacokinetic-AUC	Area under the concentration-time curve from time 0 to infinity of DB-1310	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic-Cmax	Maximum observed plasma concentration (Cmax) of DB-1310	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic-Tmax	Time to Cmax of DB-1310	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic-T1/2	Terminal elimination half-life	within 8 cycles (each cycle is 21 days)