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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05914116




Registration number
NCT05914116
Ethics application status
Date submitted
13/06/2023
Date registered
22/06/2023
Date last updated
13/09/2023

Titles & IDs
Public title
A Study of DB-1311 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-1311 in Subjects With Advanced/Metastatic Solid Tumors
Secondary ID [1] 0 0
DB-1311-O-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DB-1311

Experimental: DB-1311 Dose Level 1 - Enrolled Subjects will receive a single-dose of DB-1311 at Dose Level 1 on Day 1 of each cycle Q3W

Experimental: DB-1311 Dose Level 2 - Enrolled Subjects will receive a single-dose of DB-1311 at Dose Level 2 on Day 1 of each cycle Q3W

Experimental: DB-1311 Dose Level 3 - Enrolled Subjects will receive a single-dose of DB-1311 at Dose Level 3 on Day 1 of each cycle Q3W

Experimental: DB-1311 Dose Level 4 - Enrolled Subjects will receive a single-dose of DB-1311 at Dose Level 4 on Day 1 of each cycle Q3W

Experimental: DB-1311 Dose Level 5 - Enrolled Subjects will receive a single-dose of DB-1311 at Dose Level 5 on Day 1 of each cycle Q3W

Experimental: DB-1311 Dose Expansion 1 - Subjects with advanced/unresectable, or metastatic SCLC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.

Experimental: DB-1311 Dose Expansion 2 - Subjects with advanced/unresectable, or metastatic NSCLC who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.

Experimental: DB-1311 Dose Expansion 3 - Subjects with advanced/unresectable, or metastatic esophageal squamous cell carcinoma (ESCC) who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.

Experimental: DB-1311 Dose Expansion 4 - Subjects with advanced/unresectable, or metastatic castration-resistant prostate cancer (CRPC) who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.

Experimental: DB-1311 Dose Expansion 5 - Subjects with advanced/unresectable, or metastatic melanoma who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.

Experimental: DB-1311 Dose Expansion 6 - Subjects with other advanced or metastatic solid tumors who have progressed on or after standard systemic treatments, a 21-day treatment cycle (i.e., once every 3 weeks) via intravenous infusion will be used for DB-1311.


Treatment: Drugs: DB-1311
Administered I.V.
Intervention code [1] 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. Percentage of participants in Part 1 with DLTs
Timepoint [1] 0 0
up to 21 days after Cycle 1 Day 1
Primary outcome [2] 0 0
Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.
Timepoint [2] 0 0
Up to follow-up period, approximately 1 year 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
Maximum Tolerated Dose (MTD) of DB-1311
Timepoint [4] 0 0
12 months
Primary outcome [5] 0 0
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1311
Timepoint [5] 0 0
12 months
Primary outcome [6] 0 0
Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
Timepoint [6] 0 0
Up to follow-up period, approximately 1 year post-treatment
Primary outcome [7] 0 0
Phase 2a: 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 2a: 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
Secondary outcome [1] 0 0
Phase 1 & Phase 2a: Pharmacokinetic-AUC
Timepoint [1] 0 0
within 8 cycles (each cycle is 21 days)
Secondary outcome [2] 0 0
Phase 1 & Phase 2a: Pharmacokinetic-Cmax
Timepoint [2] 0 0
within 8 cycles (each cycle is 21 days)
Secondary outcome [3] 0 0
Phase 1 & Phase 2a: Pharmacokinetic-Tmax
Timepoint [3] 0 0
within 8 cycles (each cycle is 21 days)
Secondary outcome [4] 0 0
Phase 1 & Phase 2a: Pharmacokinetic-T1/2
Timepoint [4] 0 0
within 8 cycles (each cycle is 21 days)

Eligibility
Key inclusion criteria
1. 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).

2. Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor
that has relapsed or progressed on or after standard systemic treatments, or is
intolerable with standard treatment; or for which no standard treatment is available.

3. At least one measurable lesion as assessed by the investigator according to response
evaluation criteria in solid tumors (RECIST) version 1.1 criteria. Castrate-resistant
prostate cancer (CRPC) participants with bone only disease may be eligible on a
case-by- case basis after discussion with the Medical Monitor.

4. Has a life expectancy of = 3 months.

5. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

6. Has LVEF = 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA)
within 28 days before enrollment.

7. Is willing to provide pre-existing resected tumor samples or undergo fresh tumor
biopsy for the measurement of B7-H3 level and other biomarkers if no contraindication.

Note: there is no minimum B7-H3 expression level mandatory for entry into the study.

8. 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.

9. Male and female subjects of reproductive/childbearing potential must agree to use
adequate contraceptive methods (e.g., double barrier or intrauterine contraceptive)
during the study and for at least 4 months and 7 months after the last dose of study
drug, respectively.

10. Male subjects must not freeze or donate sperm starting at screening and throughout the
study period, and at least 4 months after the final study drug administration.

11. Female subjects must not donate, or retrieve for their own use, ova from the time of
screening and throughout the study treatment period, and for at least 7 months after
the final study drug administration.

12. SCLC participants (Phase 2a Cohort 1 ONLY):

- Pathologically documented locally advanced, or metastatic SCLC not amenable to
curative surgery or radiation.

- Relapsed/progressed on or after 2 cycles of platinum-based chemotherapy in
combination with/without anti-PD-1/anti-PD-L1 monoclonal antibody or intolerant
to completion of 2 cycles of platinum-based chemotherapy due to the toxicity for
locally advanced or metastatic disease.

13. NSCLC participants (Phase 2a Cohort 2 ONLY):

- Pathologically documented locally advanced, or metastatic NSCLC and is not
amenable to curative surgery or radiation.

- Has received prior treatment with platinum-based chemotherapy regimen and/or
anti-PD-1/PD-L1 antibody-based regimen in the advanced/unresectable, or
metastatic setting unless unable or unwilling. Participants with NSCLC known to
harbor a genomic alteration(s) other than EGFR mutation(s) (e.g., ALK
rearrangement, ROS1 rearrangement, KRAS G12C mutation, BRAF V600E mutation,
NTRK1/2/3 Gene fusion, MET Exon 14 skipping, RET rearrangement etc.) for which
treatment is available must have also received prior treatment with at least 1
genotype-directed therapy.

14. ESCC participants (Phase 2a Cohort 3 ONLY):

- Pathologically documented locally advanced, or metastatic ESCC and is not
amenable to curative surgery or radiation.

- Having received at least one prior therapy for unresectable disease. Patients
with recurrence within 6 months of completion of neoadjuvant or adjuvant therapy
will be considered as having received one prior therapy for unresectable disease.

15. CRPC participants (Phase 2a Cohort 4 ONLY):

- Pathologically documented metastatic adenocarcinoma of the prostate cancer.

- Progressive metastatic CRPC as defined: 1) castrate levels of serum testosterone
< 50 ng/dL AND 2) progressive disease as defined by PCWG3 criteria.

- Having received prior docetaxel (before or after an AR-targeted therapy).
Docetaxel rechallenge was allowed.

- Having received prior novel hormone therapy.

16. Melanoma participants (Phase 2a Cohort 5 ONLY)

• Histologically or cytologically confirmed diagnosis of unresectable Stage III or
metastatic melanoma not amenable to local therapy, must have had either:

- Previously treated with a PD-1 or PD-L1 inhibitor.

- If participants with BRAF gene mutant melanoma, must have had a prior treatment
regimen that included vemurafenib, dabrafenib, or another BRAF gene and/or
mitogen-activated protein kinase (MEK) protein inhibitor.

17. Participants with other solid tumors (Phase 2a Cohort 6 ONLY)

- Histologically or cytologically confirmed solid tumors.

- Progressed or relapsed after at least one prior standard therapeutic regimen
(Patients who have not received all approved or standard treatments for their
cancer must be informed that these alternatives to receiving DB-1311 are
available prior to consenting to participate in this trial).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unless otherwise specified, the exclusion criteria are common to both Phase 1 and Phase 2a.
Subjects who meet any of the following criteria will be excluded from the study:

1. Prior treatment with B7-H3 targeted therapy.

2. Prior treatment with antibody drug conjugate with topoisomerase inhibitor (e.g.,
trastuzumab deruxtecan).

3. Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart
Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.

4. Has a medical history of myocardial infarction or unstable angina within 6 months
before enrollment.

5. 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.

6. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT
interval.

7. Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial
pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or
current interstitial lung diseases or who are suspected to have these diseases by
imaging at screening.

8. Has a history of underlying pulmonary disorder including, but not limited to,
pulmonary emboli within 3 months of the start of study treatment, severe asthma,
severe COPD, restrictive lung disease, and other clinically significant pulmonary
compromise or requirement for supplemental oxygen.

9. Any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid
arthritis, Sjögren's, sarcoidosis) where there is documented, or a suspicion of
pulmonary involvement at the time of screening.

10. Has an uncontrolled infection requiring intravenous injection of antibiotics,
antivirals, or antifungals.

11. Know human immunodeficiency virus (HIV) infection.

12. Subjects have active viral (any etiology) hepatitis are excluded. However, subjects
with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a
positive hepatitis B surface antigen [HBsAg] test or a positive hepatitis B core
antibody test) who have a viral load below the limit quantification (HBV DNA titer <
1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be
eligible and should be discussed with the Sponsor's Medical Monitor. However, subjects
with a history of hepatitis C virus (HCV) infection who have completed curative
antiviral treatment and have a viral load below the limit of quantification are
eligible for study entry.

13. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding
will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7
days prior to enrollment.

14. Has spinal cord compression or clinically active central nervous system metastases,
defined as untreated and symptomatic, or requiring therapy with corticosteroids or
anticonvulsants to control associated symptoms. Subjects with clinically inactive
brain metastases may be included in the study. Subjects with treated brain metastases
that are no longer symptomatic and who require no treatment with corticosteroids or
anticonvulsants may be included in the study if they have recovered from the acute
toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end
of whole brain radiotherapy and study randomization.

15. Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to NCI-CTCAE version 5.0, grade = 1 or
baseline. Subjects with chronic Grade 2 toxicities (e.g., Grade 2 neuropathy) may be
eligible based on the discussion and agreement between Investigator and Sponsor.

16. Has multiple primary malignancies within 3 years before enrollment, except adequately
resected non-melanoma skin cancer (e.g., resected basal or squamous cell skin cancer),
curatively treated in-situ disease (e.g., carcinoma in situ of the cervix or breast),
other solid tumors curatively treated (e.g., superficial bladder cancer), or
contralateral breast cancer.

17. Has substance abuse or any other medical conditions that would increase the safety
risk to the subject or interfere with participation or evaluation of the clinical
study in the opinion of the investigator.

18. Has known hypersensitivity to either the drug substances or inactive ingredients in
the drug product.

19. Patients with other reasons that, in the opinion of the Investigator, make them
unsuitable to participate in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Other
Other design features
Phase
Phase 1/Phase 2
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
5/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
280
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Site 201 - Sydney
Recruitment hospital [2] 0 0
Site 202 - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
DualityBio Inc.
Address
Country

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-1311 in subjects with advanced solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05914116
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Raymond Zhao
Address 0 0
DualityBio Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michael Sun
Address 0 0
Country 0 0
Phone 0 0
86-21-26018730
Fax 0 0
Email 0 0
michael.sun@dualitybiologics.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05914116