Recruiting
Phase 1/2
A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer
Condition(s) studied
Locally Advanced Breast CancerUnresectable Breast CarcinomaMetastatic Breast Cancer
Investigational drug(s) / intervention(s)
BNT323BNT327
BNT323: Intravenous infusion
BNT327: Intravenous infusion
Study summary
This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).
Eligibility
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
* Have pathologically documented BC that:
* Is locally advanced, unresectable or metastatic.
* Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.
* Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines.
* Have measurable disease defined by RECIST v1.1.
* Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
Key Exclusion Criteria:
* Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.
* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
* Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.
* Have received any of the following therapies or drugs prior to the initiation of the study:
* Participants who have received prior treatment with BNT323.
* Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) / vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted.
* Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
* Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.
NOTE: Other protocol defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
- Part 1 - Occurrence of dose limiting toxicities (DLTs) — During the DLT evaluation period (Cycle 1), i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days
By dose level.
- Occurrence of Treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related TEAEs, treatment-related Grade ≥3 TEAEs, and treatment-related SAEs — From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
In Part 1 by dose level. In Part 2 by cohort and arm.
- Occurrence of dose interruption, reduction, and discontinuation due to TEAEs — From the time of initiation of the first dose of IMP to 90 days after the last IMP dose
In Part 1 by dose level. In Part 2 by cohort and arm.
- Part 2 - Objective response rate (ORR) — From the time of initiation of the first dose of IMP to last tumor assessment scan, i.e., up to 36 months.
ORR defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
By cohort and arm.
Trial sites (79)
| Facility | City | Region | Status |
| Beverly Hills Cancer Center |
Beverly Hills |
California |
Recruiting |
| Hoag Memorial Hospital Presbyterian |
Newport Beach |
California |
Recruiting |
| Hematology - Oncology Associates of the Treasure Coast |
Port Saint Lucie |
Florida |
Recruiting |
| University Cancer & Blood Center, LLC |
Athens |
Georgia |
Recruiting |
| Winship Cancer Institute of Emory University |
Atlanta |
Georgia |
Recruiting |
| University of Illinois Hospital & Health Sciences System |
Chicago |
Illinois |
Recruiting |
| Karmanos Cancer Institute |
Detroit |
Michigan |
Recruiting |
| Brigitte Harris Cancer Pavilion BHCP |
Detroit |
Michigan |
Recruiting |
| START Midwest, LLC |
Grand Rapids |
Michigan |
Recruiting |
| Saint Luke's Hospital of Kansas City |
Kansas City |
Missouri |
Recruiting |
| Washington University School of Medicine |
St Louis |
Missouri |
Recruiting |
| Memorial Sloan Kettering Cancer Center Basking Ridge |
Basking Ridge |
New Jersey |
Recruiting |
| Summit Medical Group |
Florham Park |
New Jersey |
Recruiting |
| Memorial Sloan Kettering Cancer Center Monmouth |
Middletown |
New Jersey |
Recruiting |
| Memorial Sloan Kettering Cancer Center Bergen |
Montvale |
New Jersey |
Recruiting |
| Memorial Sloan Kettering Cancer Center Westchester |
Harrison |
New York |
Recruiting |
| Beth Israel Comprehensive Cancer Center |
New York |
New York |
Recruiting |
| Mount Sinai Medical Center |
New York |
New York |
Recruiting |
| Icahn School of Medicine at Mount Sinai PRIME |
New York |
New York |
Recruiting |
| Memorial Sloan Kettering Hospital |
New York |
New York |
Recruiting |
| Memorial Sloan Kettering Commack |
New York |
New York |
Recruiting |
| Stony Brook University Hospital |
Stony Brook |
New York |
Recruiting |
| Memorial Sloan Kettering Cancer Center Nassau |
Uniondale |
New York |
Recruiting |
| SCRI Oncology Partners |
Nashville |
Tennessee |
Recruiting |
| Baylor Scott & White Research Institute -Texas Oncology |
Dallas |
Texas |
Recruiting |
| UT Southwestern Medical Center |
Dallas |
Texas |
Recruiting |
| South Texas Accelerated Research Therapeutics (START), LLC |
San Antonio |
Texas |
Recruiting |
| Cancer Research SA |
Adelaide |
Australia |
Recruiting |
| Box Hill Hospital |
Box Hill |
Australia |
Recruiting |
| St Vincent s Hospital Melbourne |
Fitzroy |
Australia |
Recruiting |
| CIUSSS du Saguenay-Lac-Saint-Jean |
Chicoutimi |
Canada |
Recruiting |
| London Health Sciences Centre (LHSC) - Victoria Hospital |
London |
Canada |
Recruiting |
| Sunnybrook Health Sciences Centre |
Toronto |
Canada |
Recruiting |
| BC Cancer - Vancouver |
Vancouver |
Canada |
Recruiting |
| The First Affiliated Hospital of Bengbu Medical College |
Bengbu |
China |
Recruiting |
| Jilin Cancer Hospital |
Changchun |
China |
Recruiting |
| Sichuan Cancer Hospital |
Chengdu |
China |
Recruiting |
| Sichuan Provincial People's Hospital |
Chengdu |
China |
Recruiting |
| The First Affiliated Hospital of Chongqing Medical University |
Chongqing |
China |
Recruiting |
| Huizhou First Hospital |
Huizhou |
China |
Recruiting |
+ 39 more sites — see the full list on the official registry below.