First-in-human Study of DB-1305/BNT325 for Advanced/Metastatic Solid Tumors

DualityBio

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: DB-1305/BNT325; Drug: BNT327; Combination Product: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05438329

DB-1305-O-1001

Details and patient eligibility

About

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1305/BNT325 in subjects with advanced solid tumors.

Full description

This is a multicenter, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.

Enrollment: 1,123 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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).
• Histologically or cytologically confirmed unresectable advanced/ metastatic solid tumors who have relapsed or progressed on or after standard systemic treatments or for which no standard treatment is available.
• At least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria.
• Has a life expectancy of ≥ 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Has Left Ventricular Ejection Fraction (LVEF) ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
• Has adequate organ functions within 7 days prior to Day 1 of Cycle 1.
• Has adequate treatment washout period prior to Day 1 of Cycle 1.
• Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of Trop-2 level and other biomarkers if not contraindicated.
• 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.

Exclusion criteria

• Has a medical history of symptomatic congestive heart failure (CHF) (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 non-infectious Interstitial Lung Diseases (ILD)/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has a lung-specific intercurrent clinically significant illness.
• Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
• Subjects have human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness are not eligible for enrollment; However, subjects have had HIV infection with a cluster of differentiation 4 (CD4)+ T cell count > 350 cells/µL and no history of an AIDS-defining illness are eligible for entry.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,123 participants in 30 patient groups

DB-1305/BNT325 Dose Level 1

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 1

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 2

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 2

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 3

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 3

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 4

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 4

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 5

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 5

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 6

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 6

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 7

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 7

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 in combination with pembrolizumab

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 in combination with pembrolizumab

Treatment:

Combination Product: Pembrolizumab

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 1

Experimental group

Description:

subjects with Non-Small Cell Lung Cancer (NSCLC) with actionable genetic alterations (AGAs) who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 2

Experimental group

Description:

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 3

Experimental group

Description:

Enrolled subjects with OC who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 4

Experimental group

Description:

Enrolled subjects with BC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 5

Experimental group

Description:

Enrolled subjects with Triple-Negative Breast Cancer (TNBC) who have progressed on or after standard systemic treatments and without prior treatment of sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 6

Experimental group

Description:

Enrolled subjects with TNBC with treatment failure on sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 7

Experimental group

Description:

Enrolled subjects with EC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 8

Experimental group

Description:

Enrolled subjects with malignant mesothelioma will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 9

Experimental group

Description:

Enrolled subjects with Cervical Cancer (CC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion 10

Experimental group

Description:

Enrolled subjects with pancreatic cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 11

Experimental group

Description:

Enrolled subjects with Castration-Resistant Prostate Cancer (CRPC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion PB1

Experimental group

Description:

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with pembrolizumab

Treatment:

Combination Product: Pembrolizumab

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Level 8

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 8

Treatment:

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 in combination with BNT327

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion PM1

Experimental group

Description:

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion PM2

Experimental group

Description:

Enrolled subjects with NSCLC with AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion PM3

Experimental group

Description:

Enrolled subjects with CC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion PM4

Experimental group

Description:

Enrolled subjects with OC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion PM5

Experimental group

Description:

Enrolled subjects with TNBC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 12

Experimental group

Description:

Enrolled subjects with head and neck cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 9

Experimental group

Description:

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 9

Treatment:

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion PM6

Experimental group

Description:

Enrolled subjects with NSCLC without AGA who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Treatment:

Drug: BNT327

Drug: DB-1305/BNT325