Endometrial Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of SYD985 in recurrent, advanced or metastatic endometrial cancer.
Detailed description
This is an open-label, single-arm study in patients with HER2-expressing recurrent, advanced or metastatic endometrial carcinoma. HER2-expression is defined as a 1+, 2+ or 3+ score on immunohistochemistry (IHC) or positive by in situ hybridization (ISH). Eligible patients for this study should have progressed on or after first line platinum-based chemotherapy. Patients who have had two or more lines of chemotherapy for advanced/metastatic disease are not eligible. Eligible patients will receive SYD985 until disease progression or unacceptable toxicity. Patients who have stopped study treatment for other reasons than disease progression will continue their tumor evaluations in an observation period until disease progression or start of a new anticancer therapy.
Interventions
DRUGSYD985
SYD985 powder for concentrate for solution for infusion
Sponsors
Byondis B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Females with histologically confirmed recurrent, advanced or metastatic endometrial carcinoma * Eligible patients should have progressed on or after first line platinum-based chemotherapy for advanced/metastatic endometrial cancer. Patients who have had two or more lines of chemotherapy for advanced/metastatic disease are not eligible, taking into account the following: * Patients may have received up to one additional line of chemotherapy if given in the neoadjuvant or adjuvant setting. If such treatment was completed less than 6 months prior to the current tumor recurrence or progression it is to be considered first-line treatment; * No more than one line of non-cytotoxic systemic cancer therapy (such as immunotherapy, trastuzumab or protein kinase inhibitors) is allowed. * HER2 tumor expression defined as a 1+, 2+ or 3+ score on IHC or positive by ISH * At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1); * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
Exclusion criteria
* Current or previous use of a prohibited medication as listed in the protocol; * History of infusion-related reactions and/or hypersensitivity to trastuzumab; * History of keratitis; * Severe, uncontrolled systemic disease at screening; * Left Ventricular Ejection Fraction (LVEF) \< 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab; * History of clinically significant cardiovascular disease; * Symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization; * History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 2 years | ORR is defined as the proportion of patients with an assessed best overall response of complete response or partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 2 years | PFS is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier. |
| Overall Survival (OS) | 2 years | OS is defined as the time from date of randomization to death due to any cause. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | 2 years | AEs will be graded by the investigator as assessed by CTCAE v5.0. |
Countries
Poland, Russia, Serbia, Singapore, South Korea, Ukraine, United States
Participant flow
Recruitment details
A total of 80 participants were screened, out of which 64 patients were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| SYD985 SYD985, Intravenous, every 3 weeks (Q3W)
SYD985: Powder for concentrate for solution for infusion | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 17 |
| Overall Study | Disease clinical progression | 7 |
| Overall Study | Disease progression per RECIST 1.1 | 37 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | SYD985 |
|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 7.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 0 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Region of Enrollment Poland | 4 participants |
| Region of Enrollment Russia | 14 participants |
| Region of Enrollment Serbia | 6 participants |
| Region of Enrollment Singapore | 5 participants |
| Region of Enrollment South Korea | 7 participants |
| Region of Enrollment Ukraine | 19 participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 36 / 64 |
| other Total, other adverse events | 51 / 64 |
| serious Total, serious adverse events | 12 / 64 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is defined as the proportion of patients with an assessed best overall response of complete response or partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Time frame: 2 years
Population: Efficacy analysis set (EAS) was used for the efficacy analyses. The EAS consists of a subset of the full analysis set (FAS) patients who had a baseline and at least one post-baseline tumour evaluation assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SYD985 | Objective Response Rate (ORR) | 20 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs)
AEs will be graded by the investigator as assessed by CTCAE v5.0.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SYD985 | Number of Participants With Treatment-Emergent Adverse Events (AEs) | 51 Participants |
Secondary
Overall Survival (OS)
OS is defined as the time from date of randomization to death due to any cause.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SYD985 | Overall Survival (OS) | 16.3 months |
Secondary
Progression-Free Survival (PFS)
PFS is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.
Time frame: 2 years
Population: Progression-free survival is measured for the Full Analysis Set (FAS).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SYD985 | Progression-Free Survival (PFS) | 5.6 months |