Clinical trial NCT05353361: A Phase Ib/II Study of SHR-A1811 Injection in Breast Cancer
Official title: A Phase Ib/II Multicenter, Open-Label Clinical Trial of SHR-A1811 Injection in Combination With Pyrotinib or Pertuzumab or Adebrelimab or Paclitaxel for Injection (Albumin Bound) in Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-04-29
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a multicenter, open-label, dose exploration and efficacy expansion phase Ib / II study. The first stage is the dose exploration phase, which uses the 3 + 3 escalation design; The second stage is the curative effect expansion phase.
Primary purpose: TREATMENT

Brief summary: To evaluate the safety, tolerability and efficacy of SHR-A1811 in combination with pyrotinib or pertuzumab or adebrelimab or albumin-bound paclitaxel in patients with breast cancer.


Eligibility criteria: Inclusion Criteria:

1. Women aged 18 to 75 (inclusive)
2. Breast cancer confirmed by histology or cytology.
3. ECOG score is 0 or 1
4. An expected survival of ≥ 12 weeks
5. At least one measurable lesion according to RECIST v1.1 criteria
6. Have adequate renal and hepatic function
7. Patients voluntarily joined the study and signed informed consent

Exclusion Criteria:

1. Have other malignancies within the past 5 years
2. Active central nervous system metastasis without surgery or radiotherapy
3. Presence with uncontrollable third space effusion
4. Have undergone other anti-tumor treatment within 4 weeks before the first dose
5. Immunosuppressant or systemic hormone therapy was used within 2 weeks prior to the first dose
6. Any active autoimmune disease or a history of autoimmune disease
7. A history of immune deficiency
8. Clinically significant cardiovascular disorders
9. Clinically significant history of lung disease
10. The toxicity from previous anti-tumor treatment has not recovered to ≤ grade I
11. Known hereditary or acquired bleeding tendency
12. Active hepatitis and liver cirrhosis
13. Presence of other serious physical or mental diseases or laboratory abnormalities

Primary outcomes:
measure: DLT（Phase I (dose exploration phase) ）
timeFrame: 21 days after the first administration of each subject
measure: AE（Phase I (dose exploration phase) ）
timeFrame: from Day1 to 40 or 90 days after last dose
measure: Incidence and severity of serious adverse events (SAE)（Phase I (dose exploration phase) ）
timeFrame: from Day1 to 40 or 90 days after last dose
measure: Objective response rate（Phase II (efficacy expansion phase)）
timeFrame: Two years after the last subject was enrolled in the group
Secondary outcomes:
measure: PK parameter: Cmin of SHR-A1811（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: Cmax of SHR-A1811（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: AUC0-t of SHR-A1811（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: Cmin of Pyrotinib（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: C4h of Pyrotinib（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: Cmin of Adebrelimab（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: Immunogenicity of SHR-A1811（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: Immunogenicity of Adebrelimab（Phase I secondary endpoint）
timeFrame: through study completion, an average of 2 years
measure: Objective Response Rate（Phase I secondary endpoint）
timeFrame: from first dose to disease progression or death, whichever comes first, up to 3 years
measure: Duration of response（Phase I secondary endpoint）
timeFrame: from first dose to disease progression or death, whichever comes first, up to 3 years
measure: Progression Free Survival（Phase I secondary endpoint）
timeFrame: from first dose to disease progression or death, whichever comes first, up to 3 years
measure: AE（Phase II secondary study endpoint）
timeFrame: from Day1 to 40 or 90 days after last dose
measure: Incidence and severity of serious adverse events (SAE)（Phase II secondary study endpoint）
timeFrame: from Day1 to 40 or 90 days after last dose
measure: PK parameter: Cmin, Cmax, and AUC0-t of SHR-A1811（Phase II secondary study endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: Cmin, C4h of Pyrotinib:（Phase II secondary study endpoint）
timeFrame: through study completion, an average of 2 years
measure: PK parameter: Cmin of Adebrelimab（Phase II secondary study endpoint）
timeFrame: through study completion, an average of 2 years
measure: Immunogenicity of SHR-A1811（Phase II secondary study endpoint）
timeFrame: through study completion, an average of 2 years
measure: Immunogenicity of Adebrelimab（Phase II secondary study endpoint）
timeFrame: through study completion, an average of 2 years
measure: Duration of response（Phase II secondary study endpoint）
timeFrame: from first dose to disease progression or death, whichever comes first, up to 3 years
measure: Progression Free Survival（Phase II secondary study endpoint）
timeFrame: from first dose to disease progression, or death, whichever comes first, up to 3 years
measure: Event-Free Survival Rate（Phase II secondary study endpoint）
timeFrame: from first dose to disease progression, disease recurrence, or death, whichever comes first, up to 3 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
Study officials:
References: