Clinical trial NCT06470672: Study of SHR-A1921 Combined Adebrelimab in HR-positive, HER2-negative Advanced Breast Cancer
Official title: A Phase 2 Study of SHR-A1921 Combined Adebrelimab in Endocrine Therapy-failed HR-positive, HER2-negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Hormone-receptor-positive Breast Cancer
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-06-24
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Our study is aimed to evaluate the efficacy and safety of novel ADC named SHR-A1921 combined with Adebrelimab in endocrine therapy-failed HR (Hormone Receptor)-positive, HER2-negative advanced breast cancer.


Eligibility criteria: Inclusion Criteria:

* 18 years to 75 years old, female patients with breast cancer;
* ECOG PS Score: 0\~1;
* Histologically or cytologically confirmed HR-positive, HER2-negative advanced or metastatic breast cancer;
* PD-L1 positive;
* Disease progression after at least prior 2 lines of endocrine therapy, and unable to benefit from further endocrine therapy determined by investigator, of which at least one line of CDK4/6 inhibitor-based treatment; if recurrence or metastasis within 2 years after completion of adjuvant endocrine therapy, marked as first-line treatment;
* Prior at least 1 line of systemic chemotherapy in recurrent or metastatic setting;
* Based on RECIST v1.1, at least one measurable lesion;
* Patients must have a life expectancy ≥ 3 months;
* Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
* Women of childbearing potential (WOCBP) should agree to use an effective method of contraception and no lactation from the initiation of screening to 7 months after the last dose of study therapy; WOCBP should have a negative serum pregnancy result within 7 days before the first dose of study therapy;
* Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.

Exclusion Criteria:

* Has leptomeningeal metastasis confirmed by MRI or lumbar puncture;
* Has CNS metastasis confirmed by radiology, except following conditions: ①asymptomatic brain metastasis that is not required to radiotherapy or surgery immediately; ②prior local therapy (e.g. radiotherapy or surgery) for brain or dural metastasis, of which stable disease lasting at least 4 weeks confirmed by radiography, and symptomatic therapy (e.g. hormone, mannitol, bevacizumab) has been stopped beyond 2 weeks with no clinical symptom;
* Prior anti-TROP-2 treatment;
* Has received or been receiving PD-(L)1 inhibitors and/or ADC containing a topoisomerase inhibitor-like payload;
* Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g. drainage;
* Has received antitumor surgery, radiotherapy, chemotherapy, targeted therapy or immunological therapy within 4 weeks before first dose of study therapy; has received antitumor endocrine therapy within one week before first dose of study therapy;
* Use of other antitumor systemic treatment during the study;
* Has active autoimmune disease or a history of autoimmune disease;
* Known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation;
* Has active hepatitis B (HBsAg-positive and HBV DNA≥500 IU/mL), hepatitis C (positive for HCV antibody and HCV RNA above ULN) and hepatic cirrhosis;
* Has an active infection requiring antibiotics, antiviral or antifungal treatment, or pyrexia \>38.5℃ of unknown origin during the screening period before first dose of study therapy (patients with pyrexia due to cancer could be enrolled determined by investigator);
* Receiving immunosuppressive medication, or systemic corticosteroid therapy for the purpose of immunosuppression (prednisone at \>10mg/d or equivalent dose of other corticosteroids), and continuous use within 2 weeks before the first dose of study therapy;
* Other malignancy within prior 5 years unless curatively treated with no evidence of disease for at least recent 3 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma or skin squamous cell carcinoma;
* Hypersensitivity to study therapy or any of its excipients;
* Has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis;
* Known history of uncontrolled cardiovascular clinical symptom or disease that is not well controlled;
* Has received a live vaccine within 4 weeks before first dose of study therapy, or potential to receive a live vaccine during the trial treatment;
* Other conditions that might influence the study and analysis of results in the opinion of the investigator.

Primary outcomes:
measure: ORR by investigator
timeFrame: At baseline, at the time point of every 6 weeks, up to 2 years
Secondary outcomes:
measure: DCR by investigator
timeFrame: At baseline, at the time point of every 6 weeks, up to 2 years
measure: DoR (Duration of Response)
timeFrame: Up to 2 years
measure: PFS (Progression-Free Survival)
timeFrame: Up to 2 years
measure: OS (Overall Survival)
timeFrame: Up to 2 years
measure: Safety (incidence rate of adverse event)
timeFrame: From time of informed consent provided to 3 months after the last dose of study therapy
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan Cancer Hospital
state: Shanghai
Study officials:
affiliation: Fudan Cancer Hospital
name: Hongxia Wang
role: PRINCIPAL_INVESTIGATOR
References: