Clinical trial NCT05792410: A Phase Ⅰb/Ⅱ Clinical Study of SHR-A1811 Combined With Other Therapies in Patients With HER2 Low Advanced or Metastatic Breast Cancer.
Official title: An Open, Multicenter Phase Ⅰb/Ⅱ Clinical Study of SHR-A1811 Combined With Dalpiciclib, Fulvestrant, Bevacizumab or Letrozole/Anastrozole in Patients With HER2 Low Advanced or Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: HER2 Low Advanced or Metastatic Breast Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-31
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open, multicenter, dose-finding and dose expansion investigational Phase IB/II clinical trial
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the safety, tolerability, PK and preliminary anti-tumour activity of SHR-A1811 combined with other therapies in patients with HER2 low advanced or metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

1. Ability to give informed consent, signed and dated IRB/EC approved informed consent, willing and able to comply with treatment planning visits, tests and other procedural requirements
2. When signing the informed consent, the age is 18-75 years old (including both ends), female patients who have pathologically documented HER2 low breast cancer
3. ECOG Performance Status of 0 or 1
4. Patient must have adequate tumor sample for biomarker assessment
5. At least one measurable lesion
6. Adequate organ function

Exclusion Criteria:

1. There are untreated or active central nervous system (CNS) tumor metastases
2. There was a third space effusion that could not be controlled by drainage (such as a large number of ascites, pleural effusion and pericardial effusion)
3. Major surgery within 4 weeks prior to enrollment
4. Has multiple primary malignancies within 5 years, excluding cured basal cell carcinoma of skin, cervical carcinoma in situ, papillary thyroid carcinoma, etc
5. Has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out at screening
6. Uncontrolled intercurrent illness
7. Uncontrolled or significant cardiovascular disease
8. Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
9. According to NCI-CTCAE v5.0 classification, those who have not recovered to grade Ⅰ toxicity caused by previous anti-tumour treatment

Primary outcomes:
measure: DLT(Phase I (dose-finding phase) main study endpoint)
timeFrame: At the end of cycle 1(each cycle is 28 days for SHR-A1811+ fulvestrant; each cycle is 21 days for SHR-A1811+other therapies.
measure: AE(Phase I (dose-finding phase) main study endpoint)
timeFrame: Up to follow-up period, approximately 24 months
measure: Incidence and severity of serious adverse events (SAE)(Phase I (dose-finding phase) main study endpoint)
timeFrame: Up to follow-up period, approximately 24 months
measure: Objective response rate(The main end points of the second stage (efficacy expansion stage))
timeFrame: Until progression, assessed up to approximately 24 months
Secondary outcomes:
measure: SHR-A1811 sparse PK concentrations in serum
timeFrame: While on study drug up to study completion, approximately 24 months
measure: Dalpiciclib sparse PK concentrations in plasm
timeFrame: While on study drug up to study completion, approximately 24 months
measure: Incidence of anti-drug antibodies (ADA) to SHR-A1811 over time
timeFrame: Up to follow-up period, approximately 24 months
measure: Incidence of neutralizing antibody (NAb) to SHR-A1811 over time
timeFrame: Up to follow-up period, approximately 24 months
measure: Duration of response (DoR)
timeFrame: Until progression or death, assessed up to approximately 24 months
measure: Progression-free survival (PFS)
timeFrame: Until progression or death, assessed up to approximately 24 months
Other outcomes:
Locations:
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