Trial Outcomes & Findings for Dasatinib In Combination With Trastuzumab And Paclitaxel In First Line Treatment Of Her2-Positive MBC Patients (NCT NCT01306942)

NCT ID: NCT01306942

Last Updated: 2023-03-30

Results Overview

DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03), assessed as possibly, probably or definitively related to study drugs, occurring within the first cycle of study treatment: Need of any dose modification within the first cycle due to toxicity, grade 3 or 4 neutropenia complicated with fever ≥38.5° C or infection, grade 4 neutropenia (absolute neutrophil count (ANC)\<0.5x1000000000/L) of at least 7 days duration, grade 3 thrombocytopenia complicated by hemorrhage, grade 4 thrombocytopenia, any grade 4 non-hematologic toxicity, grade 3 non-hematologic toxicities except nausea, vomiting, or diarrhea that can be controlled by appropriate medical intervention or prophylaxis, inability to resume dosing for cycle 2 at the current dose level within 14 days due to treatment related toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: Up to cycle 1
• Results posted on: 2023-03-30

Participant Flow

Ten patients were enrolled at the phase I receiving at least one cycle of the combination. Six patients were included at Dose Level (DL) 1 and four patients at DL 2. One patient at DL 1 and two patients at DL 2 had a DLT. Twenty-seven patients were included at the phase II.

Participant milestones

Measure	Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 70mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 3: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 70mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phase I STARTED	6	4	0	0
Phase I COMPLETED	1	1	0	0
Phase I NOT COMPLETED	5	3	0	0
Phase II STARTED	2	0	0	27
Phase II COMPLETED	0	0	0	11
Phase II NOT COMPLETED	2	0	0	16

Reasons for withdrawal

Measure	Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 70mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 Cohort 3: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 70mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phase I Adverse Event	2	2	0	0
Phase I Physician Decision	3	1	0	0
Phase II Adverse Event	0	0	0	6
Phase II Physician Decision	2	0	0	5
Phase II Withdrawal by Subject	0	0	0	2
Phase II Death	0	0	0	1
Phase II Not finished treatment	0	0	0	1
Phase II Protocol Violation	0	0	0	1

Baseline Characteristics

Dasatinib In Combination With Trastuzumab And Paclitaxel In First Line Treatment Of Her2-Positive MBC Patients

Baseline characteristics by cohort

Measure	Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=4 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.	Total n=39 Participants Total of all reporting groups
Age, Continuous	44.44 years n=5 Participants	49.43 years n=7 Participants	49.18 years n=5 Participants	48.48 years n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	29 Participants n=5 Participants	39 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	5 Participants n=5 Participants	4 Participants n=7 Participants	28 Participants n=5 Participants	37 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Spain	6 Participants n=5 Participants	4 Participants n=7 Participants	29 Participants n=5 Participants	39 Participants n=4 Participants
Menopausal Status Postmenopausal	2 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants	21 Participants n=4 Participants
Menopausal Status Premenopausal	4 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants
Menopausal Status Perimenopausal	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) status ECOG 0	2 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants	23 Participants n=4 Participants
Eastern Cooperative Oncology Group (ECOG) status ECOG 1	4 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants	16 Participants n=4 Participants
Hormonal Receptor Estrogen Receptor · Positive	5 Participants n=5 Participants	2 Participants n=7 Participants	22 Participants n=5 Participants	29 Participants n=4 Participants
Hormonal Receptor Estrogen Receptor · Negative	1 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	10 Participants n=4 Participants
Hormonal Receptor Progesterone Receptor · Positive	4 Participants n=5 Participants	1 Participants n=7 Participants	13 Participants n=5 Participants	18 Participants n=4 Participants
Hormonal Receptor Progesterone Receptor · Negative	2 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	21 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to cycle 1

DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory value (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03), assessed as possibly, probably or definitively related to study drugs, occurring within the first cycle of study treatment: Need of any dose modification within the first cycle due to toxicity, grade 3 or 4 neutropenia complicated with fever ≥38.5° C or infection, grade 4 neutropenia (absolute neutrophil count (ANC)<0.5x1000000000/L) of at least 7 days duration, grade 3 thrombocytopenia complicated by hemorrhage, grade 4 thrombocytopenia, any grade 4 non-hematologic toxicity, grade 3 non-hematologic toxicities except nausea, vomiting, or diarrhea that can be controlled by appropriate medical intervention or prophylaxis, inability to resume dosing for cycle 2 at the current dose level within 14 days due to treatment related toxicity.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=4 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Number of Participants With Dose Limiting Toxicity (DLT) Within the First Cycle of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I)	1 Participants	2 Participants	—

PRIMARY outcome

Timeframe: Up to cycle 1

MTD is determined by testing increasing doses of dasatinib on dose escalation cohorts 3 to 6 patients per dose level. MTD reflects the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=10 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I)	100 mg	—	—

PRIMARY outcome

Timeframe: Up to cycle 1

The RP2D was decided by the investigators taken into consideration the information obtained in the study and based on the MTD. To define the RP2D, information about toxicity observed during the full treatment were taken into consideration (relative dose intensity and toxicity observed).

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=10 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Recommended Phase II Dose (RP2D) of Dasatinib in Combination With Trastuzumab and Paclitaxel (Phase I).	100 mg	—	—

PRIMARY outcome

Timeframe: Through study treatment, an average of 24 months

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. ORR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) out of the patients who had measurable disease at baseline. Per RECIST, Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Objective Response Rate (ORR)	23 Participants	—	—

SECONDARY outcome

Timeframe: Through study treatment, an average of 24 months

Safety was assessed by standard clinical (blood pressure, pulse and body temperature, electrocardiogram (ECG), left ventricular ejection fraction (LVEF)) and laboratory tests (hematology: hemoglobin, platelet count, red blood cells (RBC), white blood cells (WBC) with differential (neutrophils) and absolute lymphocyte count, and serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, sodium, potassium, magnesium, phosphate and calcium). Adverse events grade were defined by the NCI CTCAE v 4.03.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=4 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
The Number of Participants Who Experienced Adverse Events (AE)	6 Participants	4 Participants	29 Participants

SECONDARY outcome

Timeframe: Through study treatment, an average of 24 months

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CBR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) plus stable disease lasting at least 6 months out of the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
To Evaluate the Clinical Benefit Rate (CBR)	24 Participants	—	—

SECONDARY outcome

Timeframe: Through study treatment, an average of 24 months

TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Time to Progression (TTP)	23.9 months Interval 14.9 to The upper limit of the Confidence Interval (CI) was censored due to upper limit has not been reached.	—	—

SECONDARY outcome

Timeframe: Through study treatment, an average of 24 months

PFS is defined as the time from the date of the first dose to the first date of objectively determined progressive disease or death from any cause. For patients not known to have died as of the data cut-off date and who do not have objectively-determined progressive disease, PFS will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression or death, PFS will be censored at the date of last objective progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Progression Free Survival (PFS)	23.9 months Interval 10.3 to The upper limit of the Confidence Interval (CI) was censored due to upper limit has not been reached.	—	—

SECONDARY outcome

Timeframe: Through study treatment, an average of 24 months

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an >=30% decrease in the sum of the longest diameter of target lesions. For responding patients not known to have died as of the data cut-off date and who do not have progression, RD will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, RD will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=23 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Response Duration (RD)	18.4 months Interval 7.4 to The upper limit of the Confidence Interval (CI) was censored due to upper limit has not been reached.	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 2 and day 18

Population: Two participant samples for cycle 1 day 18 could not be obtained.

To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1).

The mean profiles of dasatinib plasma concentrations were determined by dose and PK occasion.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=3 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Dasatinib Maximun Plasma Concentration (Cmax) Value (Pharmacokinetics (PK) Phase I) Day 2 Dasatinib alone	191.0 ng/mL Standard Deviation 92.1	422.3 ng/mL Standard Deviation 56.4	—
Dasatinib Maximun Plasma Concentration (Cmax) Value (Pharmacokinetics (PK) Phase I) Day 18 Dasatinib in combination P and T	78.4 ng/mL Standard Deviation 51.1	314.4 ng/mL Standard Deviation 153.6	—

SECONDARY outcome

Timeframe: Cycle 1 day 2 and day 18

Population: Two participant samples for cycle 1 day 18 could not be obtained.

To assess the influence of the concomitant administration of paclitaxel and trastuzumab on dasatinib PKs, we compared dasatinib exposures alone (first PK occasion: day 2 of cycle 1) or combined (second PK occasion: day 18 on cycle 1).

The area under the plasma concentration-time curve from time zero to 8 hours post dose (AUC0-8) were calculated in all treated patients, as the dasatinib plasmatic half-life is very short and concentrations at 24 hours post dose could only be quantified in some patients.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=3 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Dasatinib Area Under the Plasma Concentration-time Curve (AUC) Value (Pharmacokinetics (PK) Phase I) Day 2 Dasatinib alone	530.6 ng·h/mL Standard Deviation 237.1	1159.2 ng·h/mL Standard Deviation 128.3	—
Dasatinib Area Under the Plasma Concentration-time Curve (AUC) Value (Pharmacokinetics (PK) Phase I) Day 18 Dasatinib in combination P and T	248.1 ng·h/mL Standard Deviation 156.7	1047.3 ng·h/mL Standard Deviation 682.8	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours

Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-SRC proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-SRC (Tyr416). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=16 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylated SRC (p-SRC) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II)	0.36 Absorbance 450 nm Standard Deviation 0.378	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours

Sequential peripheral blood mononuclear cells (PBMCs) on Cycle 1 Day 1 before treatment and 8 hours (h) after treatment (0h and 8h) were assessed to explore changes in the expression of p-AKT proteins measured by enzyme-linked immunosorbent assay (ELISA). For ELISA analyses, a duplicate of 100 µg of the extract was used to detect p-AKT (Ser473). ELISA is a plate-based assay technique designed for detecting and quantifying proteins. The instrumentation used for protein signal-detection is an absorbance spectrophotometer (AS), which measures Absorbance (A). A is the quantity of light absorbed by a sample. As different compounds absorb light at different wavelengths, an AS can be used to distinguish compounds by analyzing the pattern of wavelengths absorbed by a given sample. Additionally, the amount of light absorbed is directly proportional to the concentration of absorbing compounds in that sample, so an AS can also be used to determine concentrations of compounds in the sample.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=16 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylated AKT (p-AKT) Protein Expression Change in Peripheral Blood Mononuclear Cells After 8 Hours of Treatment (Phase II)	0.04 Absorbance 450 nm Standard Deviation 0.09	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 and cycle 2 day 1

Population: Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1.

p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 and cycle 2 day 1, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=5 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 0 hours	103 score on a scale Interval 90.0 to 116.0	—	—
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 8 hours	28 score on a scale Interval 10.0 to 46.0	—	—
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) H-score Cycle 1, day 4	14 score on a scale Interval 4.0 to 24.0	—	—
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase I) H-score Cycle 2, day 1	20 score on a scale Interval 8.0 to 32.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours

Population: Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours.

p-SRC was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of SRC.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase II) H-score 8 hours	27 score on a scale Interval 10.0 to 44.0	—	—
Phosphorylation Status of Phosphorylated SRC (p-SRC) in Skin After Treatment (Phase II) H-score 0 hours	105 score on a scale Interval 83.0 to 127.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours and cycle 2 day 1

Population: Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours and cycle 2 day 1.

p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, and cycle 2 day 1, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=5 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 0 hours	65 score on a scale Interval 31.0 to 99.0	—	—
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) H-score Cycle 2, day 1, 8 hours	13 score on a scale Interval 8.0 to 18.0	—	—
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 8 hours	20 score on a scale Interval 10.0 to 30.0	—	—
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase I) H-score Cycle 1, day 4, 8 hours	10 score on a scale Interval 10.0 to 10.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours

Population: Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours.

p-AKT was analyzed in the skin biopsies taken at cycle 1, day 1 at 0 hours and 8 hours, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of AKT

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase II) H-score 0 hours	70 score on a scale Interval 40.0 to 100.0	—	—
Phosphorylation Status of Phosphorylated AKT (p-AKT) in Skin After Treatment (Phase II) H-score 8 hours	20 score on a scale Interval 10.0 to 30.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours

Population: Skin biopsies could only be obtained in 5 participants at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours and cycle 2 day 1 at 8 hours.

p-ERK was analyzed in the skin biopsies taken at cycle 1 day 1 at 0 hours and 8 hours, cycle 1 day 4 at 8 hours, and cycle 2 day 1 at 8 hours, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=5 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 8 hours	20 score on a scale Interval 11.0 to 29.0	—	—
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) H-score Cycle 1, day 4, 8 hours	14 score on a scale Interval 4.0 to 24.0	—	—
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) H-score Cycle 1, day 1, 0 hours	63 score on a scale Interval 50.0 to 76.0	—	—
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase I) H-score Cycle 2, day 1, 8 hours	11 score on a scale Interval 0.0 to 24.0	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 0 hours and at 8 hours

Population: Skin biopsies could only be obtained in 6 participants at cycle 1 day 1 at 0 hours and 8 hours.

Phosphorylated extracellular signal-regulated kinases (p-ERK) 1 and 2 expression were analyzed in the skin biopsies taken at the cycle 1 day 1 at 0 hours and 8 hours, only in patients accepting to participate.

A semi-quantitative H-score (or "histo" score) determined by the estimation of the percentage of tumour cells positively stained with low, medium, or high staining intensity. The final score is determined after applying a weighting factor to each estimate. The formula used is H-score = (low %) × 1 + (medium %) × 2 + (high %) × 3, and the results ranged from minimum 0 to maximum 300.

Aim: to confirm the mechanism of action identified in preclinical models where the combination of dasatinib and trastuzumab show a statistically significant reduction in the phosphorylated levels of ERK

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase II) H-score 0 hours	60 score on a scale Interval 49.0 to 71.0	—	—
Phosphorylation Status of Phosphorylated ERK (p-ERK) in Skin After Treatment (Phase II) H-score 8 hours	16 score on a scale Interval 6.0 to 26.0	—	—

SECONDARY outcome

Timeframe: Cycle 1

Efficacy (ORR, CBR, TTP, RD and PFS) was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria, and were correlated Lymphocytes, that were measured in the weekly hematology analyses performed within the first cycle.

Outcome measures

Measure	Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=6 Participants Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=4 Participants Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 Participants Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Number of Participants With Correlation Between Lymphocytosis and Efficacy.	0 Participants	0 Participants	0 Participants

Adverse Events

Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2

Serious events: 6 serious events

Other events: 29 other events

Deaths: 1 deaths

Serious adverse events

Measure	Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=6 participants at risk Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=4 participants at risk Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 participants at risk Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Cardiac disorders Angina	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Injury, poisoning and procedural complications Overdose	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Infections and infestations Soft tissue and skin infection	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Infections and infestations Catheter related infection	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
General disorders Sudden death	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Febrile syndrome respiratory focus	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Number of events 1 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.

Other adverse events

Measure	Dasatinib 100mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=6 participants at risk Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	Dasatinib 140mg + Trastuzumab 2mg/kg + Paclitaxel 80mg/m2 n=4 participants at risk Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.	PhaseII Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2 n=29 participants at risk Phase II with recommended Phase II Dose (RP2D) Dasatinib 100mg: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Two patients from phase I with measurable disease and RP2D were included in the phase II analyses.
Skin and subcutaneous tissue disorders Alopecia	66.7% 4/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	44.8% 13/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Alanine aminotransferase increased	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	44.8% 13/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
General disorders Fatigue	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	75.0% 3/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	17.2% 5/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Vascular disorders Hypertension	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	17.2% 5/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Metabolism and nutrition disorders Hyponatremia	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	6.9% 2/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	75.0% 3/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Gastrointestinal disorders Nausea	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	24.1% 7/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Ejection Fraction Decreased	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	24.1% 7/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Blood and lymphatic system disorders Anemia	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	44.8% 13/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Neutrophil Count Decreased	66.7% 4/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	55.2% 16/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Weight Gain	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	24.1% 7/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Metabolism and nutrition disorders Hypocalcemia	33.3% 2/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	24.1% 7/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Metabolism and nutrition disorders Anorexia	66.7% 4/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	20.7% 6/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Alanine Aminotransferase Increased	66.7% 4/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	75.0% 3/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	58.6% 17/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Aspartate Aminotransferase Increased	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	100.0% 4/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	69.0% 20/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Red Blood Cells Count Decrease	83.3% 5/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	100.0% 4/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	93.1% 27/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations White Blood Cell Decreased	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	41.4% 12/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Lymphopenia	33.3% 2/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	75.0% 3/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	3.4% 1/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	6.9% 2/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Respiratory, thoracic and mediastinal disorders Cough	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	17.2% 5/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
General disorders Fever	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	13.8% 4/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
General disorders Edema limbs	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	50.0% 2/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	10.3% 3/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	66.7% 4/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	6.9% 2/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Alkaline phosphatase increased	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	31.0% 9/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Nervous system disorders Headache	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	17.2% 5/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Gastrointestinal disorders Mucositis oral	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	27.6% 8/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Nervous system disorders Peripheral sensory neuropathy	50.0% 3/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	25.0% 1/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	37.9% 11/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Investigations Activated Partial Thromboplastin Time Prolonged	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	20.7% 6/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.
Metabolism and nutrition disorders Hypomagnesemia	16.7% 1/6 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	0.00% 0/4 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.	27.6% 8/29 • Through study treatment, an average of 12 months AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation os study treatment.

Additional Information

Scientific Director / Medical Lead / Project Manager

Spanish Breast Cancer Research Group

Phone: +34916592870

Email: geicam@geicam.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60