A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors
PHASE1PHASE2RECRUITING
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.
Study details:
This is a multicenter, non-randomized (Except for Dose Expansion 1 and Dose Expansion 9 cohorts), open-label, multiple-dose, 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 MTD/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 HER2-expressing malignant solid tumors.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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.
- 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.
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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT05150691
Intervention or treatment
BIOLOGICAL: DB-1303/BNT323
DRUG: Pertuzumab Injection
DRUG: Ritonavir
DRUG: Itraconazole
Conditions
- HER2-positive Advanced Solid Tumor
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Research sites nearby
Closest Location:
Helios Clinical Research
Select from list below to view details:
Helios Clinical Research
Cerritos, California, United States
California Research Institute
Los Angeles, California, United States
Sharp Memorial Hospital
San Diego, California, United States
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
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Who is running the clinical trial?
DI
DualityBio Inc.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: DB-1303/BNT323 Dose Level 1
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 2
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 3
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 4
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 5
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 1
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 2
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 3
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 4
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 5
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 6
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Level 7
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 6
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 7
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 8
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 9
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 10
| Biological: DB-1303/BNT323, Drug: Ritonavir, Drug: Itraconazole |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 11
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 12
| Biological: DB-1303/BNT323, Drug: Pertuzumab Injection |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 13
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 14
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 15
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 16
| Biological: DB-1303/BNT323 |
EXPERIMENTAL: DB-1303/BNT323 Dose Expansion 17
| Biological: DB-1303/BNT323 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. | Percentage of participants in Part 1 with DLTs | up to 21 days after C1D1 |
| Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0 | 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). | Up to Safety Follow-Up visit, approximately 35 days post-treatment |
| Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0 | Up to follow-up period, approximately 1 year post-treatment |
| Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 | MTD on the data collected during Part 1 | Up to Safety Follow-Up visit, approximately 35 days post-treatment |
| Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 | RP2D of DB-1303 based on the data collected during Part 1 | Up to Safety Follow-Up visit, approximately 35 days post-treatment |
| Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0 | 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). | Up to follow-up period, approximately 1 year post-treatment |
| Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0 | Up to follow-up period, approximately 1 year post-treatment |
| Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. | The percentage of subjects who had a best response of CR or PR, for Part 2 only which was maintained ≥4 weeks. | Up to follow-up period, approximately 1 year post-treatment |
| 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 | Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Ritonavir) | up to safety follow-up visit, approx. 35 days post-treatment |
| 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. | Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Itraconazole) | up to safety follow-up visit, approx. 35 days post-treatment |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 & Phase 2: Pharmacokinetic-AUC | Area under the concentration-time curve from time 0 to infinity of DB-1303 | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & Phase 2: Pharmacokinetic-Cmax | Maximum observed plasma concentration (Cmax) of DB-1303 | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & Phase 2: Pharmacokinetic-Tmax | Time to Cmax of DB-1303 | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & Phase 2: Pharmacokinetic-T1/2 | Terminal elimination half-life | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & Phase 2: Pharmacokinetic-Ctrough | Trough concentration of DB-1303 | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & Phase 2: Pharmacodynamics-ADA | Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline. | Up to safety follow up visit, approx. 35 days post-treatment |
| Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1 | Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1. | Up to follow-up period, approximately 1 year post-treatment |
| Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1 | 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 | Up to follow-up period, approximately 1 year post-treatment |
| Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1 | 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 | Up to follow-up period, approximately 1 year post-treatment |
| Phase 2: Time on Therapy | The duration of time from participant receiving first dose of study drug to the last dose + 21 days | Up to 21 days after the participant's last dose |
| Phase 2: Percent change in target lesions as assessed by RECIST 1.1 | The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1 | Up to follow-up period, approximately 1 year post-treatment |
| Phase 1 and 2 Cohort b only: Progression-Free Survival | Time from subject receiving the first dose to disease progression or death by any cause | Up to follow-up period, approximately 1 year post-treatment |
| Phase 1 and 2 Cohort b only: Overall Survival | Time from subject receiving the first dose to death by any cause | Up to follow-up period, approximately 1 year post-treatment |
| Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1 | The percentage of subjects who had a best response of CR or PR | Up to follow-up period, approximately 1 year post-treatment |
| 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 | The percentage of subjects who had a best response of CR or PR, for Cohort 2b only | Up to follow-up period, approximately 1 year post-treatment |
| To evaluate the safety of DB-1303 with/without ritonavir or itraconazole | 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). | Up to follow-up period, approximately 1 year post-treatment |
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References
Clinical Trials Gov: A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid TumorsOther trials to consider
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