Clinical trial NCT05438329: First-in-human Study of DB-1305/BNT325 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-1305 in Subjects With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: DualityBio Inc.
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2022-06-29
Enrollment: 1123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
timeFrame: up to 21 days after Cycle 1 Day 1
measure: Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.
timeFrame: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
measure: Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
timeFrame: Up 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
measure: Maximum Tolerated Dose (MTD) of DB-1305/BNT325
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Phase 1: RP2D of DB-1305/BNT325
timeFrame: From first study treatment administration until the initiation of Phase 2a, approximately up to 12 months.
measure: Phase 2a: Percentage of Participants with TEAEs as assessed by CTCAE v5.0.
timeFrame: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
measure: Phase 2a: Percentage participants with SAEs as assessed by CTCAE v5.0.
timeFrame: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
measure: Phase 2a: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
timeFrame: 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 outcomes:
measure: Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator per RECIST 1.1
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: disease-control rate (DCR)
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: time to response (TTR)
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator per RECIST 1.1
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: overall survival (OS)
timeFrame: with 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic parameters: (the area under the concentration-time curve from the time zero to the last quantifiable concentration [AUC0-last] of DB-1305/BNT325
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau [AUC0-tau] of DB-1305/BNT325
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: peak observed concentration [Cmax] of DB-1305/BNT325
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax [Tmax] of DB-1305/BNT325
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration [Ctrough] of DB-1305/BNT325
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: anti-drug antibody (ADA) prevalence: the proportion of subjects who are ADA positive at any point in time (at baseline and post-baseline). ADA incidence: the proportion of subjects having treatment-emergent ADA.
timeFrame: within 8 cycles (each cycle is 21 days)
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: Site 103
state: California
city: Los Angeles
country: United States
facility: Site 108
state: California
city: Margate
country: United States
facility: D&H Cancer Research Center Llc
state: Florida
city: Plantation
country: United States
facility: Site 109
state: Florida
city: Tamarac
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Detroit
country: United States
facility: Site 106
state: Michigan
city: New York
country: United States
facility: Site 102
state: New York
city: Canton
country: United States
facility: Site 101
state: Ohio
city: Nashville
country: United States
facility: Site 105
state: Tennessee
city: Arlington
country: United States
facility: Site 110
state: Texas
city: Houston
country: United States
facility: Site 104
state: Texas
city: Fairfax
country: United States
facility: Site 107
state: Virginia
city: Bengbu
country: China
facility: Site 211
state: Anhui
city: Hefei
country: China
facility: Site 217
state: Anhui
city: Fuzhou
country: China
facility: Site 213
state: Fujian
city: Nanning
country: China
facility: Site 209
state: Guangxi
city: Guigang
country: China
facility: Site 221
state: Guanxi
city: Zhengzhou
country: China
facility: Site 202
state: Henan
city: Wuhan
country: China
facility: Site 205
state: Hubei
city: Ganzhou
country: China
facility: Site 208
state: Jiangxi
city: Changchun
country: China
facility: Site 201
state: Jilin
city: Shenyang
country: China
facility: Site 210
state: Liaoning
city: Jinan
country: China
facility: Site 216
state: Shandong
city: Linyi
country: China
facility: Site 212
state: Shandong
city: Shanghai
country: China
facility: Site 207
state: Shanghai
city: Chengdu
country: China
facility: Site 206
state: Sichuan
city: Tianjin
country: China
facility: Site 203
state: Tianjin
city: Taizhou
country: China
facility: Site 220
state: Zhejiang
city: Guangzhou
country: China
facility: Site 219
city: Mayaguez
country: Puerto Rico
facility: BRCR GLOBAL Puerto Rico LLC.
Study officials:
affiliation: DualityBio Inc.
name: Lily Hu
role: STUDY_DIRECTOR
References: