Locally Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
Breast Neoplasm, HER3 Expression, Hormone Receptor Positive Breast Cancer, Triple Negative Breast Cancer, Metastatic breast cancer, locally advanced breast cancer
Brief summary
This study is to evaluate safety and efficacy of an antibody drug conjugate U3-1402 (patritumab deruxtecan) in patients with locally advanced or metastatic breast cancer (MBC).
Detailed description
U3-1402 (Patritumab Deruxtecan) is an antibody drug conjugate comprising a recombinant fully human anti HER3 monoclonal antibody linked to a linker containing topoisomerase I inhibitor. This is a phase II study of U3-1402 (patritumab deruxtecan) in subjects with MBC. The study will be conducted in 3 parts (Part A , Part B, and Part Z). All enrolled subjects in Part A will undergo pretreatment biopsies to determine if subjects with particular biomarker expression (ER/PR/HER2/HER3) show preliminary efficacy. Part B will enroll subgroups of participants that are metastatic, hormone receptor-positive (HR+) HER2-negative or triple-negative (mTNBC) regardless of HER3 expression that were defined from Part A analysis. Part Z will enroll participants with HER2- positive (HER2+) MBC.
Interventions
DRUGU3-1402
All subjects will receive 5.6 mg/kg U3-1402 (Patritumab Deruxtecan) intravenously on day 1 of every 3 weeks. One cycle is defined as 3 weeks.
Sponsors
SCRI Development Innovations, LLC
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria: Inclusion criteria for Part A and B (HER2-negative) and Part Z (HER2-positive) cohorts: 1. Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses 2. Women and men at least 18 years-of-age at the time of signature of the informed consent form (ICF) 3. Histologically documented locally advanced or metastatic breast cancer 4. Triple-negative breast cancer (TNBC) patients should have received at least 1 but no more than 5 prior lines of chemotherapy in the metastatic setting 5. Parts A and B patients only: Patients with HR+ HER2-negative MBC should have received prior treatment with endocrine therapy +CDK 4/6 inhibitor. No limit to prior endocrine therapy regimens, but no more than 2 prior chemotherapy regimens in the metastatic setting are allowed. HR+ = Estrogen receptor (ER) and/or Progesterone (PgR) positivity that are defined as ≥1% of cells expressing HR via IHC analysis. HER2 negativity is defined as either of the following: IHC 0, IHC 1+, or IHC 2+/in situ hybridization (ISH) negative. 6. Part B patients only: Patients with HER2-negative MBC will be included into one of the following 2 subgroups: 1) MBC HR+, HER2-, regardless of HER3 expression, who have received trastuzumab deruxtecan and/or sacituzumab govitecan, or, 2) mTNBC, regardless of HER3 expression, who have received sacituzumab govitecan and/or datopotamab deruxtecan. 7. Part Z patients only: should have documented HER2-positive expression as per American Society of Clinical Oncology - College of American Pathologists guidelines based on local testing. 8. Part Z patients only: should have had prior treatment with at least 2 anti-HER2 therapies, 1 of which must be trastuzumab deruxtecan. These patients must have experienced disease progression after receiving trastuzumab deruxtecan. 9. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (bone-only disease excluded) 10. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed ≥4 weeks prior to initiation of study treatment (2 weeks for patients who received palliative radiation therapy), there is no evidence of central nervous system disease progression on a scan or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy for the treatment of brain metastases 11. Willingness to undergo pre-treatment biopsy and on-treatment biopsies; must have a tumor amenable to pre-treatment biopsy (unless archived tissue is available and was obtained within 2 months prior to starting treatment) and on-treatment biopsy (excludes bone lesions and previously irradiated lesions) 12. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 13. Has adequate organ function within 7 days before the start of study treatment, defined as: * Platelet count ≥100 × 109/L * Hemoglobin (Hb) ≥9 g/dL (transfusion and/or growth factor support allowed) * Absolute neutrophil count ≥1.5 × 109/L * Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 × the upper limit of normal (ULN), except for patients on coumadin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-international normalized ratio (INR) within therapeutic range as deemed appropriate by the Investigator * Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min as calculated using the modified Cockcroft-Gault equation; confirmation of creatinine clearance is only required when creatinine is \>1.5 × ULN * AST/ALT ≤3 × ULN (if liver metastases are present, ≤5 × ULN) * Total bilirubin ≤1.5 × ULN if no liver metastases or \<3 × ULN in the presence of documented Gilbert's syndrome or liver metastases * Serum albumin ≥2.5 g/dL 14. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for at least 7 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in Participants With HER2-negative MBC (Part A and Part B) | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Overall Response Rate (ORR) is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) out of all treated participants. Confirmed response is two consecutive CR or PR at least 4 weeks apart according to RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of lesion diameters. |
| Progression-Free Survival at 6 Months (PFS-6) in Participants With HER2-negative MBC (Part A and Part B) | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Progression-Free Survival at 6 months (PFS-6) is defined as the rate of patients who survive progression-free for at least 6 months per RECIST version (v) 1.1. Per RECIST V1.1, progressive disease is defined as a ≥20% increase in target lesions and ≥5mm increase in size from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment- Emergent Adverse Events to Assess Safety and Tolerability | Every 3 weeks, up to 45 months. | The safety and tolerability of U3-1402 (Patritumab Deruxtecan) was assessed through the analysis of the reported incidence of treatment-emergent AEs. Treatment-emergent AEs are those with an onset on or after the initiation of study therapy up to 40 days after last day of treatment, and will be graded according to NCI CTCAE 5.0. |
| Duration of Response (DOR) | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Duration of response (DOR) is calculated only for participants who experienced a Complete Response (CR) or Partial Response (PR) per RECIST V1.1 and is defined as the median number of months of duration from the first documented response \[complete response (CR) or partial response (PR)\] to the date of disease progression (PD) according to the RECIST V1.1 criteria or death due to any cause. Per RECIST V1.1, CR=disappearance of all target lesions, PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of target lesion diameters, PD is ≥20% increase in target lesions and ≥5mm from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions. Kaplan-Meier estimates were used to calculate the 95% confidence intervals for duration of response. |
| Progression-Free Survival (PFS) | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Progression Free Survival (PFS) is defined as the time from start of study treatment to the date of the first documented disease progression (PD) according to the RECIST V1.1 criteria or death due to any cause. Per RECIST V1.1, PD is ≥20% increase in target lesions and ≥5mm increase from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions. |
| Clinical Benefit Rate (CBR) | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | CBR is defined as the rate of participants with complete response (CR), partial response (PR), or best overall response of stable disease (SD) for ≥ 6 months according to the RECIST v 1.1 criteria. Per RECIST V1.1: A CR is defined as the disappearance of all target and non-target lesions. A PR is defined as ≥30% decrease in the sum of diameters of target lesions from the baseline sum. A SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). |
| Overall Response Rate (ORR) in Participants With HER2-positive (HER2+) MBC After Progression on Trastuzumab Deruxtecan: Part Z | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Overall Response Rate (ORR) is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) out of all treated participants. Confirmed response is two consecutive CR or PR at least 4 weeks apart according to RECIST v1.1 criteria. CR=disappearance of all target and non-target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of lesion diameters. |
| Progression-Free Survival at 6 Months (PFS-6) in Participants With HER2-positive (HER2+) MBC: Part Z | Assessed every 6 weeks for the first 6 months then every 9 weeks thereafter until disease progression or death or study discontinuation, up to 45 months. | Progression-Free Survival at 6 months (PFS-6) is defined as the rate of patients who survive progression-free for at least 6 months per RECIST version (v) 1.1. Per RECIST V1.1, progressive disease is defined as a ≥20% increase in target lesions and ≥5mm increase in size from smallest sum, appearance of any new lesions, or unequivocal progression of non-target lesions. |
Countries
United States
Contacts
STUDY_CHAIRErika Hamilton, MD
SCRI Development Innovations, LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 57 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 91 Participants |
| Region of Enrollment United States | 60 Participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 60 | 4 / 40 | 3 / 21 |
| other Total, other adverse events | 60 / 60 | 39 / 40 | 21 / 21 |
| serious Total, serious adverse events | 12 / 60 | 7 / 40 | 5 / 21 |
Outcome results
None listed