Advanced Solid Tumor
Conditions
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.
Interventions
DRUGDB-1305/BNT325
Administered Injection of Vein (I.V.)
COMBINATION_PRODUCTPembrolizumab
Administered I.V.
DRUGBNT327
Administered I.V.
Sponsors
BioNTech SE
DualityBio Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | up to 21 days after Cycle 1 Day 1 | Percentage of participants in Part 1 with DLTs |
| Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0. | Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first. | Percentage of participants with TEAEs in Part 1 graded according to NCI CTCAE v5.0 |
| Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | Up 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first. | Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0 |
| Maximum Tolerated Dose (MTD) of DB-1305/BNT325 | At the end of Cycle 1 (each cycle is 21 days) | MTD on the data collected during Part 1 |
| Phase 1: RP2D of DB-1305/BNT325 | From first study treatment administration until the initiation of Phase 2a, approximately up to 12 months. | RP2D of DB-1305/BNT325 based on the data collected during Part 1 |
| Phase 2a: Percentage of Participants with TEAEs as assessed by CTCAE v5.0. | Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first. | Percentage of participants with TEAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3) |
| Phase 2a: Percentage participants with SAEs as assessed by CTCAE v5.0. | Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first. | Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3) |
| Phase 2a: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (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. | The percentage of subjects who had a best response rating of CR and PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 & Phase 2a: peak observed concentration [Cmax] of DB-1305/BNT325 | within 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: peak observed concentration \[Cmax\] of DB-1305/BNT325 |
| Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax [Tmax] of DB-1305/BNT325 | within 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax \[Tmax\] of DB-1305/BNT325 |
| Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1 | with 8 cycles (each cycle is 21 days) | Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1 |
| 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. | within 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: anti-drug antibody (ADA) prevalence of DB-1305: the proportion of subjects who are ADA positive at any point in time (at baseline and post-baseline). ADA incidence of DB-1305: the proportion of subjects having treatment-emergent ADA. |
| Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration [Ctrough] of DB-1305/BNT325 | within 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration \[Ctrough\] of DB-1305/BNT325 |
| Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator per RECIST 1.1 | with 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator (by BICR in cohort 3 in Phase 2a) per RECIST 1.1 |
| Phase 1 & Phase 2a: disease-control rate (DCR) | with 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: disease-control rate (DCR) |
| Phase 1 & Phase 2a: time to response (TTR) | with 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: time to response (TTR) |
| Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator per RECIST 1.1 | with 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator (by BICR in cohort 3 in Phase 2a) per RECIST 1.1 |
| Phase 1 & Phase 2a: overall survival (OS) | with 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: overall survival (OS) |
| 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 | within 8 cycles (each cycle is 21 days) | 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 |
| Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau [AUC0-tau] of DB-1305/BNT325 | within 8 cycles (each cycle is 21 days) | Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau \[AUC0-tau\] of DB-1305/BNT325 |
Countries
China, Puerto Rico, United States
Contacts
Primary ContactTyler McCullars
Backup ContactCathy Li
Outcome results
None listed