Trial Title:
Platform Study of ADC Rechallenge in ADC-treated Metastatic Breast Cancer
NCT ID:
NCT06649331
Condition:
Advanced Breast Cancer
Metastatic Breast Cancer
Triple Negative Breast Cancer (TNBC)
HER2-negative Breast Cancer
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Conditions: Keywords:
platform trial
adaptive design
antibody-conjugated drugs (ADCs)
Bayesian predictive probability
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SHR-A1811
Description:
A HER2-directed ADC, via intravenous (into the vein) infusion per protocol.
Arm group label:
A
Intervention type:
Drug
Intervention name:
SHR-A1921
Description:
A TROP2-directed ADC, via intravenous (into the vein) infusion per protocol.
Arm group label:
B
Intervention type:
Drug
Intervention name:
SHR-A2009
Description:
A HER3-directed ADC, via intravenous (into the vein) infusion per protocol.
Arm group label:
C
Intervention type:
Drug
Intervention name:
SHR-A2102
Description:
A Nectin4-directed ADC, via intravenous (into the vein) infusion per protocol.
Arm group label:
D
Summary:
This is a prospective, open-label, multicenter, phase II platform trial. The purpose of
this study is to test the safety and effectiveness of the antibody-conjugated drugs
(ADCs) in patients with advanced breast cancer who had previously used
antibody-conjugated drugs.
Detailed description:
This is a prospective, open-label, multicenter, phase II platform trial. The purpose of
this study is to test the safety and effectiveness of the antibody-conjugated drugs
(ADCs) in patients with advanced breast cancer who had previously received ADCs.
The primary endpoint is objective response rate (ORR). This trial aims to learn whether
ADC rechallenge works in treating in ADC-treated metastatic breast cancer and identify
which ADC works better for subsets on the basis of molecular characteristics and ADC
treatment history of their disease with high ORR. Study drugs involved in this study
including but not limited to: SHR-A1811 (HER2 ADC), SHR-A1921 (TROP2 ADC), SHR-A2009
(HER3 ADC) and SHR-A2102 (Nectin 4 ADC).
This platform trial is adaptive design. Novel ADC regimens with sufficiently high
activities that show a high Bayesian predictive probability will graduate from the trial
with their corresponding biomarker signature(s). ADCs will be dropped if they show a low
probability of improved efficacy with any biomarker signature. New ADCs will enter as
those that have undergone testing complete their evaluation.
Based on the existing four ADC treatment cohorts on this platform, a maximum of 120
subjects were planned to be enrolled in each ADC treatment cohort. According to the
previous ADC treatment history and target, the subjects were randomly assigned to each
cohort by adaptive randomization. On the basis of previous clinical data at our center,
we limited the enrollment of a minimum of 10 participants per cohort to avoid
underrepresentation of any cohort. During the course of the study, ORR will be evaluated
periodically for every additional 10 results according to the Bayesian monitoring method,
and the proportion of random assignment to each cohort will be adjusted according to the
calculated posterior probability using response-adaptive randomization (RAR). Graduation
(successful validation) or elimination (failed validation) of ADC rechallenge treatment
will be considered according to the posterior probability of an ADC cohort and the data
of primary efficacy endpoint, secondary efficacy endpoints and safety endpoints.
Additional targeted regimens may be added to the platform regimen as feasible as assessed
by the investigators, and the protocol will be modified accordingly at that time.
The efficacy was evaluated by CT or MRI every 6 weeks (±1 week) according to RECIST 1.1.
Subjects with CR or PR were required to have radiologic response confirmation at least 4
weeks. Tumor assessments were performed every 9 weeks (±1 week) after 36 weeks of
treatment until disease progression, initiation of new antineoplastic therapy, withdrawal
of consent, loss to follow-up, death, or the end of the study, whichever occurred first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years;
2. Locally advanced breast cancer (unable to undergo radical local treatment) or
recurrent metastatic breast cancer;
3. Previously received ADCs;
4. The most recent pathology results will be considered for enrollment according to
local testing of ER, PR and HER2. Participants with any hormone receptor (HR) status
will be allowed on study.
5. Prior endocrine therapy: Participants with HR-positive breast cancer must have
received prior CDK4/6 inhibitor;
6. Participants must have measurable disease per RECIST 1.1.
7. The functions of the main organs are basically normal and meet the following
conditions:
I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion
within 14 days); The ANC acuity 1.5 x 10^9 / L; PLT acuity 75 x 10^9 / L; II.
Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of
normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤
5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance > 50 ml/min
(Cockcroft-Gault formula); III. LVEF≥50%
8. They have not received radiotherapy, molecular targeted therapy, or surgery within 3
weeks before the start of the study, and have recovered from the acute toxicity of
previous treatment (if surgery was performed, the wound has healed completely); No
peripheral neuropathy or grade I peripheral neurotoxicity; Participants may have
discontinued all CDK4/6 inhibitor at least 14 days prior to study treatment
initiation. Prior endocrine therapy does not require washout.
9. ECOG score ≤2, and life expectancy ≥3 months;
10. Fertile female subjects were required to use a medically approved contraceptive
method during the study treatment period and for at least 3 months after the last
use of the study drug;
11. Subjects volunteered to join the study, signed informed consent, had good
compliance, and cooperated with follow-up.
Exclusion Criteria:
1. Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were
used in the first 3 weeks of treatment, except bisphosphonate (which can be used for
bone metastasis);
2. Uncontrolled central nervous system metastases (indicating symptomatic or
symptomatic treatment with glucocorticoids or mannitol);
3. A history of clinically important or uncontrolled heart disease, including
congestive heart failure, angina pectoris, myocardial infarction, or ventricular
arrhythmia within the last 6 months;
4. Presence of the third space effusion (such as massive ascites, pleural effusion,
pericardial effusion) that cannot be controlled by drainage or other methods;
5. Participants with who had used immunosuppressive agents or systemic corticosteroids
within 2 weeks before the first dose (dose> 10mg/day prednisone or other
corticosteroids at the physiological dose of the drug), excluding nasal spray or
inhaled corticosteroids;
6. Presence of any active autoimmune disease or a history of autoimmune disease with
potential relapse;
7. Known human immunodeficiency virus (HIV) infection that is not well controlled;
8. Known active hepatitis B (HBV DNA≥2000 IU/mL or 104 copies/mL) and hepatitis C
(positive for hepatitis C antibodies and HCV-RNA above the lower detection limit of
the assay);
9. Persistent grade 1 or higher adverse reactions caused by previous treatments. The
exception to this is hair loss or something the researchers don't think should be
ruled out. Such cases should be clearly documented in the investigator's notes;
10. Underwent major surgery (except minor outpatient procedures, such as placement of
vascular access) within 3 weeks of the first course of trial treatment;
11. Pregnant or lactating patients;
12. Malignancy (except basal cell carcinoma of the skin, which has been cured, and
carcinoma in situ of the cervix) in the past 5 years;
13. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to the study agent or accompanying supportive medications;
14. Serious physical or mental illnesses or laboratory abnormalities that may increase
the risk of participating in the study or interfere with the study results
15. Deemed by the investigator to be ineligible for participation in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Breast cancer institute of Fudan University Cancer Hospital
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhimin Shao, M.D
Phone:
86-21-64175590
Email:
zhimingshao@yahoo.com
Investigator:
Last name:
Xiyu Liu, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Lei Fan, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Zhimin Shao, M.D.
Email:
Principal Investigator
Start date:
October 21, 2024
Completion date:
September 2027
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06649331
