Solid Tumors
Conditions
Keywords
B7-H3, PD-L1/VEGF-A, TROP2 (Trophoblast cell surface antigen 2), ADC (antibody-drug conjugate), HNSCC (head and neck squamous cell carcinoma), HCC (hepatocellular carcinoma), Melanoma, NSCLC(non-small cell lung cancer), OC (ovarian cancer)
Brief summary
A Phase II, Multicenter, Open-Label Trial of DB-1311 in combination with BNT327 or DB-1305 in Participants with Advanced/Metastatic Solid Tumors
Detailed description
This is a phase II, multicenter, open-label, two-part trial designed to evaluate the safety and preliminary efficacy of DB-1311 in combination with BNT327 or DB-1311 in combination with DB-1305 in targeted participants. Participants with recurrent, progressive as well as advanced, metastatic hepatocellular carcinoma (HCC), cervical cancer (CC), melanoma, head and neck squamous cell carcinoma (HNSCC), platinum-resistant ovarian cancer (PROC) or non-small cell lung cancer (NSCLC), platinum-sensitive ovarian cancer (PSOC), pancreatic ductal carcinoma (PDAC), breast cancer, colorectal cancer (CRC), or metastatic castration resistant prostate cancer (mCRPC) are eligible to participate in the trial.
Interventions
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
* Adults aged ≥ 18 years or acceptable age according to local regulations at the time of voluntarily signing informed consent. * At least one measurable lesion as assessed by the Investigator according to RECIST v1.1 criteria. * Has a life expectancy of ≥ 3 months. * Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 * Has adequate organ function within 7 days prior to enrollment/randomization, * Has adequate treatment washout period prior to the first dose of trial treatment. * For HCC patients: Histological/cytological confirmed diagnosis of HCC or clinically confirmed diagnosis of HCC; Has a Child-Pugh class A liver score. * For CC patients: Has persistent, recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology * For Melanoma patients: Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic melanoma. * For PROC patients (Cohort A): Participants must have a confirmed diagnosis of OC, primary peritoneal cancer, or fallopian tube cancer, all of which with high-grade serous histology. Patients must have platinum-resistant disease. * For HNSCC patients: Histologically or cytologically confirmed recurrent (recurrent disease that is not amendable to curative treatment with local/ or systemic therapies)/ (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. * For NSCLC patients: Pathologically documented Stage IIIB or IIIC NSCLC not amenable for radical surgery or definitive chemoradiation or Stage IV NSQ NSCLC. Not harboring an EGFR-sensitizing mutation or ALK gene rearrangements or other onco-driver gene mutations * For PSOC: Must have PSOC, defined as radiographically documented disease recurrence or progression occurring \>6 months after completion of the last dose of platinum-based chemotherapy. * For PDAC: Participants must have histologically or cytologically confirmed metastatic PDAC., who have progressed after at least one prior line of standard systemic treatment ((≥2L PDAC).) * For breast cancer: * HR+/HER2-low or HR+/HER2-ultralow or HR+/HER2-negative BC participants: Pathologically or cytologically documented HR-positive unresectable or metastatic BC with HER2-low, HER2-ultralow or HER2-negative expression. * Triple negative breast cancer (TNBC): Pathologically or cytologically documented unresectable or metastatic TNBC * For mCRC: Participants who have metastatic CRC and have relapsed or progressed after 1 prior line of systemic treatment including a fluoropyrimidine plus oxaliplatin with or without anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) or anti-epidermal growth factor receptor mAb therapy, as clinically indicated, or have relapsed or progressed after 2 lines of therapy if the participant has received targeted therapy * For mCRPC: Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and mCRPC
Exclusion criteria
* 1\. Prior treatment with B7H3 targeted therapy. * Prior treatment with antibody-drug conjugate with topoisomerase inhibitor. * Is a candidate to locoregional treatment with potential to induce complete or near complete response and prolonged tumor control, per investigator's assessment. * Has an uncontrolled concomitant or intercurrent illness, that in the opinion of the investigator, contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring AEs. * Has uncontrolled or significant cardiovascular disease. Has clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy. * Has a history of (non-infectious) ILD/pneumonitis. * Any autoimmune, connective tissue or inflammatory disorders. * Has spinal cord compression or clinically active central nervous system (CNS) metastases. * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Number of participants with Dose Limiting Toxicities (DLTs). | During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days |
| Part 1: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) | up to follow up period, e.g. up to 72 months. |
| Part 2: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) [By arm and dose level] | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 2: Objective response rate (ORR), defined as the proportion of participants in whom a confirmed Complete response (CR) or PR is observed as best overall response (per RECIST 1.1 based on the investigator's assessment)by arm and dose level. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: ORR, defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST 1.1 based on the investigator's assessment). | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Duration of response (DoR) per RECIST 1.1 based on the investigator's assessment. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Overall survival (OS) | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Disease-control rate (DCR) per RECIST 1.1 based on the investigator's assessment. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Time to response (TTR) per RECIST 1.1 based on the investigator's assessment. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Progression-free survival (PFS) per RECIST 1.1 based on the investigator's assessment. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1: Cancer antigen 125 (CA-125) response rate assessed per Gynecological Cancer Intergroup (GCIG) criteria in participants with platinum-resistant ovarian cancer (PROC). | From the time of initiation of the first dose of IMP to end of Part 1 |
| Part 1: Cancer antigen 125 (CA-125) response rate assessed per Gynecological Cancer Intergroup (GCIG) criteria in participants with PROC. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 2:Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Time to reach maximum observed concentration (Tmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Time to reach maximum observed concentration (Tmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Terminal elimination half-life (t1/2) of DB-1311/BNT324 total ADC, total antibody and unconjugated P1021 in combination with BNT327. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Terminal elimination half-life (t1/2) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and 2: Anti-drug antibody (ADA) prevalence: the proportion of participants who are ADA positive at any point in time (at baseline and post-baseline). | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
| Part 1 and Part 2: ADA incidence: the proportion of participants having treatment-emergent ADA. | From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months |
Countries
Australia, China, Taiwan, United States
Contacts
CONTACTJay Ma
CONTACTQiaoli Jiang
Outcome results
None listed