A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors

NCT05150691
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
796
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Lead sponsor
DualityBio Inc.
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Start date
2022-01-31
clinicaltrials.gov
Number of sites
102
clinicaltrials.gov

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.
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Short title
A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors
clinicaltrials.gov
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-1303/BNT323 in Patients With Advanced/Metastatic Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2027-10-01
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First posted
2021-12-09
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Registry last updated
2026-08-27
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Primary completion date
2027-08-01
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Start date
2022-01-31
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Participants
796
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Participant count basis
Estimated
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Planned participants
796
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Protocol amendments
10
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Number of sites
102
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Registry sponsor category
Industry
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Lead sponsor
DualityBio Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05150691
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ClinicalTrials.gov ID
NCT05150691
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.

    Timeframe: up to 21 days after C1D1

    Percentage of participants in Part 1 with DLTs

  2. Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0

    Timeframe: Up to Safety Follow-Up visit, approximately 35 days post-treatment

    Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

  3. Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0

  4. Phase 1: Maximum Tolerated Dose (MTD) of DB-1303

    Timeframe: Up to Safety Follow-Up visit, approximately 35 days post-treatment

    MTD on the data collected during Part 1

  5. Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303

    Timeframe: Up to Safety Follow-Up visit, approximately 35 days post-treatment

    RP2D of DB-1303 based on the data collected during Part 1

  6. Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Phase 2: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

  7. Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0

  8. Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The percentage of subjects who had a best response of CR or PR, for Part 2 only which was maintained ≥4 weeks.

  9. 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

    Timeframe: up to safety follow-up visit, approx. 35 days post-treatment

    Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Ritonavir)

  10. 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.

    Timeframe: up to safety follow-up visit, approx. 35 days post-treatment

    Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Itraconazole)

  1. Phase 1 & Phase 2: Pharmacokinetic-AUC

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Area under the concentration-time curve from time 0 to infinity of DB-1303

  2. Phase 1 & Phase 2: Pharmacokinetic-Cmax

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Maximum observed plasma concentration (Cmax) of DB-1303

  3. Phase 1 & Phase 2: Pharmacokinetic-Tmax

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Time to Cmax of DB-1303

  4. Phase 1 & Phase 2: Pharmacokinetic-T1/2

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Terminal elimination half-life

  5. Phase 1 & Phase 2: Pharmacokinetic-Ctrough

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Trough concentration of DB-1303

  6. Phase 1 & Phase 2: Pharmacodynamics-ADA

    Timeframe: Up to safety follow up visit, approx. 35 days post-treatment

    Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline.

  7. Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1.

  8. Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The duration of time from date of first CR or PR to date of progressive disease or death due to any cause, whichever comes first using RECIST V1.1

  9. Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The duration of time when receiving the first dose of study drug to the first date that is evaluated as either CR or PR using RECIST V1.1

  10. Phase 2: Time on Therapy

    Timeframe: Up to 21 days after the participant's last dose

    The duration of time from participant receiving first dose of study drug to the last dose + 21 days

  11. Phase 2: Percent change in target lesions as assessed by RECIST 1.1

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1

  12. Phase 1 and 2 Cohort b only: Progression-Free Survival

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Time from subject receiving the first dose to disease progression or death by any cause

  13. Phase 1 and 2 Cohort b only: Overall Survival

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Time from subject receiving the first dose to death by any cause

  14. Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The percentage of subjects who had a best response of CR or PR

  15. 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

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    The percentage of subjects who had a best response of CR or PR, for Cohort 2b only

  16. To evaluate the safety of DB-1303 with/without ritonavir or itraconazole

    Timeframe: Up to follow-up period, approximately 1 year post-treatment

    Percentage of Participants with Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAE), TEAEs \>/= G3, or TEAEs leading to dose reduction, interruption or discontinuation, Adverse Events of Special Interest, (AESIs), abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Helios Clinical ResearchCerritos, United StatesActive, not recruiting
  • California Research InstituteLos Angeles, United StatesActive, not recruiting
  • Sharp Memorial HospitalSan Diego, United StatesActive, not recruiting
  • Washington Cancer Institute at MedStar Washington Hospital CenterWashington D.C., United StatesActive, not recruiting
  • Advanced Research LLCCoral Springs, United StatesActive, not recruiting
  • The Oncology Institute of Hope and InnovationLakeland, United StatesActive, not recruiting
  • D&H Cancer Research Center LLCMargate, United StatesActive, not recruiting
  • HCA Mercy HospitalMiami, United StatesWithdrawn
  • BRCR Medical Center Inc.Plantation, United StatesActive, not recruiting
  • BRCR Medical Center Inc.Tamarac, United StatesActive, not recruiting
  • Southeastern Regional Medical Center, LLCNewnan, United StatesActive, not recruiting
  • Kapi'olani Medical Center for Women and ChildrenHonolulu, United StatesActive, not recruiting
  • University of ChicagoChicago, United StatesActive, not recruiting
  • Women's Cancer CareCovington, United StatesWithdrawn
  • Holy Cross HospitalSilver Spring, United StatesWithdrawn
  • Massachusetts General HospitalBoston, United StatesActive, not recruiting
  • Beth Israel Deaconess Medical CenterBoston, United StatesActive, not recruiting
  • Profound Research LLC/Michigan Hematology & Oncology ConsultantsDearborn, United StatesWithdrawn
  • David C. Pratt Cancer CenterSt Louis, United StatesActive, not recruiting
  • Women's Cancer Center of NevadaLas Vegas, United StatesWithdrawn
  • Northwell HealthLake Success, United StatesWithdrawn
  • Laura & Isaac Perlmutter Cancer Center at NYC Langone HealthNew York, United StatesActive, not recruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesActive, not recruiting
  • North Shore Hematology Oncology Associate P.C. DBA New York Cancer and Blood SpecialistsShirley, United StatesActive, not recruiting
  • Regional Medical Oncology CenterWilson, United StatesWithdrawn

And 77 more, listed on the interactive page.

Sources for sites
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Related records

Drugs (4)

Collaborators (1)

Lead sponsors (1)

Conditions (10)

Targets (5)