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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
Date last updated
3/10/2024

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
31/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2027
Actual
Sample size
Target
766
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
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
China
State/province [22] 0 0
Anhui
Country [23] 0 0
China
State/province [23] 0 0
Beijing
Country [24] 0 0
China
State/province [24] 0 0
Changchun
Country [25] 0 0
China
State/province [25] 0 0
Fujian
Country [26] 0 0
China
State/province [26] 0 0
Guangdong
Country [27] 0 0
China
State/province [27] 0 0
Guangxi
Country [28] 0 0
China
State/province [28] 0 0
Hebei
Country [29] 0 0
China
State/province [29] 0 0
Hehan
Country [30] 0 0
China
State/province [30] 0 0
Henan
Country [31] 0 0
China
State/province [31] 0 0
Hubei
Country [32] 0 0
China
State/province [32] 0 0
Hunan
Country [33] 0 0
China
State/province [33] 0 0
Jiangsu
Country [34] 0 0
China
State/province [34] 0 0
Jiangxi
Country [35] 0 0
China
State/province [35] 0 0
Liaoning
Country [36] 0 0
China
State/province [36] 0 0
Shaanxi
Country [37] 0 0
China
State/province [37] 0 0
Shandong
Country [38] 0 0
China
State/province [38] 0 0
Shangdong
Country [39] 0 0
China
State/province [39] 0 0
Shanghai
Country [40] 0 0
China
State/province [40] 0 0
Tianjin
Country [41] 0 0
China
State/province [41] 0 0
Yunnan
Country [42] 0 0
China
State/province [42] 0 0
Zhejiang
Country [43] 0 0
Puerto Rico
State/province [43] 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
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors that express HER2.
Trial website
https://clinicaltrials.gov/study/NCT05150691
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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05150691