HER2-positive Advanced Solid Tumor
Conditions
Keywords
HER2, HER2-positive, HER2-positive Breast Cancer, HER2-positive Gastric Cancer, HER2-positive Endometrial Cancer, HER2-positive Biliary Tract Cancer, HER2-positive Advanced Solid Tumor, HER2 low, HER2 high, metastatic cancer, HER2-positive GEJ, Uterine serous papillary carcinoma, USPC, recurrent cancer, carcinoma, neoplasms, breast neoplasms, gastrointestinal neoplasms, endometrial neoplasms, biliary tract neoplasms, Antineoplastic Agents, Biological, stomach cancer, bile duct cancer, Cholangiocarcinoma, liver cancer, liver neoplasms, NSCLC, Non-Small Cell Lung Cancer, NSCLC HER2 mutation, HER2 Low Breast Cancer
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.
Detailed description
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.
Interventions
BIOLOGICALDB-1303/BNT323
Administered IV
Administered IV
DRUGRitonavir
Administered oral
DRUGItraconazole
Administered oral
Sponsors
DualityBio Inc.
BioNTech SE
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. | up to 21 days after C1D1 | Percentage of participants in Part 1 with DLTs |
| Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0 | 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). |
| Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | 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 |
| Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 | Up to Safety Follow-Up visit, approximately 35 days post-treatment | MTD on the data collected during Part 1 |
| Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 | Up to Safety Follow-Up visit, approximately 35 days post-treatment | RP2D of DB-1303 based on the data collected during Part 1 |
| Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0 | 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). |
| Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. | 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 |
| Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. | 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. |
| 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 | 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) |
| 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. | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 & Phase 2: Pharmacokinetic-AUC | 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 |
| Phase 1 & Phase 2: Pharmacokinetic-Cmax | Up to safety follow up visit, approx. 35 days post-treatment | Maximum observed plasma concentration (Cmax) of DB-1303 |
| Phase 1 & Phase 2: Pharmacokinetic-Tmax | Up to safety follow up visit, approx. 35 days post-treatment | Time to Cmax of DB-1303 |
| Phase 1 & Phase 2: Pharmacokinetic-T1/2 | Up to safety follow up visit, approx. 35 days post-treatment | Terminal elimination half-life |
| Phase 1 & Phase 2: Pharmacokinetic-Ctrough | Up to safety follow up visit, approx. 35 days post-treatment | Trough concentration of DB-1303 |
| Phase 1 & Phase 2: Pharmacodynamics-ADA | 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. |
| Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1 | 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. |
| Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1 | 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 |
| Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1 | 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 |
| Phase 2: Time on Therapy | 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 |
| Phase 2: Percent change in target lesions as assessed by RECIST 1.1 | 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 |
| Phase 1 and 2 Cohort b only: Progression-Free Survival | 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 |
| Phase 1 and 2 Cohort b only: Overall Survival | Up to follow-up period, approximately 1 year post-treatment | Time from subject receiving the first dose to death by any cause |
| Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1 | Up to follow-up period, approximately 1 year post-treatment | The percentage of subjects who had a best response of CR or PR |
| 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 | 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 |
| To evaluate the safety of DB-1303 with/without ritonavir or itraconazole | 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). |
Countries
Australia, China, Puerto Rico, South Korea, Taiwan, United States
Contacts
CONTACTBritney Winterberger
Outcome results
None listed