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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05150691




Registration number
NCT05150691
Ethics application status
Date submitted
11/11/2021
Date registered
9/12/2021

Titles & IDs
Public title
A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors
Scientific title
A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303/BNT323 in Patients With Advanced/Metastatic Solid Tumors
Secondary ID [1] 0 0
DB-1303-O-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-positive Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - DB-1303/BNT323
Treatment: Drugs - Pertuzumab Injection
Treatment: Drugs - Ritonavir
Treatment: Drugs - Itraconazole

Experimental: DB-1303/BNT323 Dose Level 1 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 2 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 3 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 4 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 5 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 1 - Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 2 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 3 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 4 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 5 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 6 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Level 7 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 6 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 7 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 8 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 9 - Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 10 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir or itraconazole to assess the DDI potential

Experimental: DB-1303/BNT323 Dose Expansion 11 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 12 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 13 - Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Experimental: DB-1303/BNT323 Dose Expansion 14 - China Only:Subjects who were previously treated with trastuzumab and taxane will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W


Treatment: Other: DB-1303/BNT323
Administered IV

Treatment: Drugs: Pertuzumab Injection
Administered IV

Treatment: Drugs: Ritonavir
Administered oral

Treatment: Drugs: Itraconazole
Administered oral

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
Timepoint [1] 0 0
up to 21 days after C1D1
Primary outcome [2] 0 0
Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
Timepoint [2] 0 0
Up to Safety Follow-Up visit, approximately 35 days post-treatment
Primary outcome [3] 0 0
Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
Timepoint [3] 0 0
Up to follow-up period, approximately 1 year post-treatment
Primary outcome [4] 0 0
Phase 1: Maximum Tolerated Dose (MTD) of DB-1303
Timepoint [4] 0 0
Up to Safety Follow-Up visit, approximately 35 days post-treatment
Primary outcome [5] 0 0
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303
Timepoint [5] 0 0
Up to Safety Follow-Up visit, approximately 35 days post-treatment
Primary outcome [6] 0 0
Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
Timepoint [6] 0 0
Up to follow-up period, approximately 1 year post-treatment
Primary outcome [7] 0 0
Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
Timepoint [7] 0 0
Up to follow-up period, approximately 1 year post-treatment
Primary outcome [8] 0 0
Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
Timepoint [8] 0 0
Up to follow-up period, approximately 1 year post-treatment
Primary outcome [9] 0 0
Phase 2 (Dose Expansion 10 only): To evaluate the effect of ritonavir on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors
Timepoint [9] 0 0
up to safety follow-up visit, approx. 35 days post-treatment
Primary outcome [10] 0 0
Phase 2 (Dose Expansion 10 only): To evaluate the effect of itraconazole on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors.
Timepoint [10] 0 0
up to safety follow-up visit, approx. 35 days post-treatment
Secondary outcome [1] 0 0
Phase 1 & Phase 2: Pharmacokinetic-AUC
Timepoint [1] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [2] 0 0
Phase 1 & Phase 2: Pharmacokinetic-Cmax
Timepoint [2] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [3] 0 0
Phase 1 & Phase 2: Pharmacokinetic-Tmax
Timepoint [3] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [4] 0 0
Phase 1 & Phase 2: Pharmacokinetic-T1/2
Timepoint [4] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [5] 0 0
Phase 1 & Phase 2: Pharmacokinetic-Ctrough
Timepoint [5] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [6] 0 0
Phase 1 & Phase 2: Pharmacodynamics-ADA
Timepoint [6] 0 0
Up to safety follow up visit, approx. 35 days post-treatment
Secondary outcome [7] 0 0
Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1
Timepoint [7] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [8] 0 0
Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1
Timepoint [8] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [9] 0 0
Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1
Timepoint [9] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [10] 0 0
Phase 2: Time on Therapy
Timepoint [10] 0 0
Up to 21 days after the participant's last dose
Secondary outcome [11] 0 0
Phase 2: Percent change in target lesions as assessed by RECIST 1.1
Timepoint [11] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [12] 0 0
Phase 1 and 2 Cohort b only: Progression-Free Survival
Timepoint [12] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [13] 0 0
Phase 1 and 2 Cohort b only: Overall Survival
Timepoint [13] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [14] 0 0
Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1
Timepoint [14] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [15] 0 0
Phase 2 Cohort b Only: Percentage of ORR as assessed by IRC and as assessed by investigator based on RECIST 1.1 for HER2-expressing subjects and in subjects with prior ICI treatment
Timepoint [15] 0 0
Up to follow-up period, approximately 1 year post-treatment
Secondary outcome [16] 0 0
To evaluate the safety of DB-1303 with/without ritonavir or itraconazole
Timepoint [16] 0 0
Up to follow-up period, approximately 1 year post-treatment

Eligibility
Key inclusion criteria
* Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
* At least 1 measurable lesion (per RECIST 1.1)
* Provide signed informed consent
* ECOG performance status (PS) of 0-1.
* LVEF = 50% by ECHO or MUGA
* Adequate organ functions
* Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing.
* Life expectancy of = 3 months.

Additional Inclusion Criteria for Part 2 Expansion Group 9:

1. Has pathologically documented advanced/unresectable, recurrent, or metastatic EC (including UCS and USPC) and has progressed on or after at least 1 line of systemic treatment including platinum-based therapy and exposure to ICI but no more than prior 3 lines of therapy for advanced/unresectable, or metastatic disease. Note: endocrine therapy will not qualify as a systemic therapy line.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of symptomatic CHF (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.
* History of myocardial infarction or unstable angina within 6 months before Day 1.
* Average QTcF > 450 ms in males and > 470 ms in females
* History of clinically significant lung diseases
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
* HIV infection with AIDS defining illness or active viral hepatitis.
* Clinically active brain metastases
* Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade = 1 or baseline.
* A known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
* Part 2 (expansion) Only:Multiple primary malignancies within 3 years, except adequately resected non- melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Scientia Clinical Research LTD - Randwick
Recruitment hospital [2] 0 0
Macquarie Clinical Trials Unit - Sydney
Recruitment hospital [3] 0 0
Integrated Clinical Oncology Network Pty Ltd (Icon) - South Brisbane
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
China
State/province [21] 0 0
Anhui
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Changchun
Country [24] 0 0
China
State/province [24] 0 0
Fujian
Country [25] 0 0
China
State/province [25] 0 0
Guangdong
Country [26] 0 0
China
State/province [26] 0 0
Guangxi
Country [27] 0 0
China
State/province [27] 0 0
Hebei
Country [28] 0 0
China
State/province [28] 0 0
Hehan
Country [29] 0 0
China
State/province [29] 0 0
Henan
Country [30] 0 0
China
State/province [30] 0 0
Hubei
Country [31] 0 0
China
State/province [31] 0 0
Hunan
Country [32] 0 0
China
State/province [32] 0 0
Jiangsu
Country [33] 0 0
China
State/province [33] 0 0
Jiangxi
Country [34] 0 0
China
State/province [34] 0 0
Liaoning
Country [35] 0 0
China
State/province [35] 0 0
Shaanxi
Country [36] 0 0
China
State/province [36] 0 0
Shandong
Country [37] 0 0
China
State/province [37] 0 0
Shangdong
Country [38] 0 0
China
State/province [38] 0 0
Shanghai
Country [39] 0 0
China
State/province [39] 0 0
Tianjin
Country [40] 0 0
China
State/province [40] 0 0
Yunnan
Country [41] 0 0
China
State/province [41] 0 0
Zhejiang
Country [42] 0 0
Puerto Rico
State/province [42] 0 0
Mayaguez

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
DualityBio Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
BioNTech SE
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Britney Winterberger
Address 0 0
Country 0 0
Phone 0 0
+1-513-403-8568
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.