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The purpose of this study is to evaluate the efficacy and safety of Sintilimab plus anlotinib combined with chemotherapy as neoadjuvant therapy in participants who have triple negative breast cancer (TNBC). After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Sintilimab + anlotinib + chemotherapy) based on schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 4-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence. The primary outcome measure is pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sintilimab + Anlotinib + Chemotherapy | Experimental | Experimental: Sintilimab + Anlotinib + Chemotherapy Participants receive Sintilimab every 3 weeks (Q3W) + Anlotinib d1-14 (Q3W) + (Nab paclitaxel weekly + carboplatin (Q3W) x 4 cycles followed by epirubicin + cyclophosphamide Q3W x 4 cycles) as neoadjuvant therapy prior to surgery. After surgery, the subjects will continue to receive sintilimab treatment until one year has elapsed since the start of neoadjuvant therapy (that is, they will receive sintilimab treatment at least 17 times). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sintilimab | Drug | 200mg on days 1 (Q3W) of the neoadjuvant and adjuvant phase of the study; IV injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery | pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery. | Up to approximately 30-32 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Residual cancer burden (RCB) | Residual cancer burden (RCB) | Up to approximately 30-32 weeks |
| Event-free Survival (EFS) as assessed by Investigator | EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause. |
| Measure | Description | Time Frame |
|---|---|---|
| European Orgnisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. | Up to approximately 48-52 weeks |
Inclusion Criteria:
T1c, N1-N2 T2, N0-N2 T3, N0-N2 T4a-d, N0-N2
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NeoSACT | Guangzhou | Guangdong | 510080 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40541191 | Derived | Zhang L, Yang L, Ge Y, Zhu Z, Chen B, Yang C, Gao H, Yang M, Zhu T, Wang K. Neoadjuvant anlotinib/sintilimab plus chemotherapy in triple-negative breast cancer (NeoSACT): Phase 2 trial. Cell Rep Med. 2025 Jul 15;6(7):102193. doi: 10.1016/j.xcrm.2025.102193. Epub 2025 Jun 19. |
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Patient enrollment followed a Simon two-stage design.The Simon design required 11 patients for the first stage and called for termination at stage 1 if there were less than 5 responders (Pathological complete response, pCR) among 11 patients. Otherwise, if seven or more responders were identified in up to 11 patients, additional 20 patients would be enrolled. Treatment was considered of clinical interest if, at the end of the second stage, there were more than 16 responders among 31 patient.
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| Anlotinib | Drug | 12mg on d1-14 of Cycles 1-8 (Q3W) of the neoadjuvant phase of the study; po. Arotinib is a small molecule multi-target TKI, which exerts its effect by inhibiting angiogenesis, a critical component of tumour growth and metastasis. |
|
| Nab paclitaxel | Drug | 100 mg/m² on day 1, 8 and 15 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection. |
|
| Carboplatin | Drug | AUC 5 on days 1 of Cycles 1-4 (Q3W) of the neoadjuvant phase of the study; IV injection. |
|
| Epirubicin | Drug | 90 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection. |
|
| Cyclophosphamide | Drug | 600 mg/m² on day of Cycles 5-8 (Q3W) of the neoadjuvant phase of the study; IV injection. |
|
| Up to approximately 3 years |
| Overall survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 5 years |
| Immune response biomarkers | PDL1, CD8, Tils, HRD... | Up to approximately 60 weeks |
| Percentage of participants who experience an adverse event (AE) | An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. | Up to approximately 60 weeks |
| EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR42) score | The EORTC-QLQ-BR42 is a 42-item questionnaire developed to assess the quality of life of breast cancer patients. And it is now a fully validated EORTC questionnaire and can be used in conjunction with the QLQ-C30. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. | Up to approximately 48-52 weeks |
| Patient Health Questionnaire-9 (PHQ-9) | PHQ-9 is a nine-item questionnaire for screening depression symptoms and measuring its severity rated on a scale of 0 (not at all), 1 (several days), 2 (more than half the days) or 3(nearly every day). The severity of depressive symptoms in this study will be classified into three subgroups according to the PHQ-9 score: no depression (0-4), mild depression (5-9) and moderate-to-severe depression (≥10). The cutoff score and its severity of PHQ-9 had been extensively applied to screen symptoms of depression in studies involving patients with cancer. | Up to approximately 48-52 weeks |
| Generalized Anxiety Disorder 7-item (GAD-7) | GAD-7 is a seven-item questionnaire for screening anxiety symptoms and measuring its severity rated on a scale of 0 (not at all), 1 (several days), 2 (more than half the days) or 3 (nearly every day). The severity of anxiety symptoms in this study will be classified into three subgroups based on the GAD-7 scores: no anxiety (0-4), mild anxiety (5-9) and moderate-to-severe anxiety(≥10).GAD-7 had shown satisfactory validity and reliability for screening anxiety symptoms with cancer. | Up to approximately 48-52 weeks |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000632826 | sintilimab |
| C000625192 | anlotinib |
| D013660 | Taxes |
| D016190 | Carboplatin |
| D015251 | Epirubicin |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D004317 | Doxorubicin |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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