Trial Outcomes & Findings for Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer. (NCT NCT02789657)

NCT ID: NCT02789657

Last Updated: 2022-05-19

Results Overview

pCR is pathologic complete response defined as ypT0/isN0 on pathology report

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

at surgery post approximately 18 weeks of treatment

Results posted on

2022-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental: Optimal- 18 Weeks 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Sub-optimal no AC 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Overall Study STARTED	27	3	2
Overall Study COMPLETED	25	3	2
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: Optimal- 18 Weeks 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Optimal With AC Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal no AC 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Overall Study Withdrawal by Subject	2	0	0	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Optimal- 18 Weeks n=27 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC n=3 Participants 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Optimal With AC Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal no AC n=2 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=27 Participants	0 Participants n=3 Participants	0 Participants	0 Participants n=2 Participants	0 Participants n=32 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=27 Participants	3 Participants n=3 Participants	0 Participants	2 Participants n=2 Participants	27 Participants n=32 Participants
Age, Categorical >=65 years	5 Participants n=27 Participants	0 Participants n=3 Participants	0 Participants	0 Participants n=2 Participants	5 Participants n=32 Participants
Age, Continuous	51 years n=27 Participants	48 years n=3 Participants	—	45 years n=2 Participants	50 years n=32 Participants
Sex: Female, Male Female	27 Participants n=27 Participants	3 Participants n=3 Participants	0 Participants	2 Participants n=2 Participants	32 Participants n=32 Participants
Sex: Female, Male Male	0 Participants n=27 Participants	0 Participants n=3 Participants	0 Participants	0 Participants n=2 Participants	0 Participants n=32 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	27 participants n=27 Participants	3 participants n=3 Participants	—	2 participants n=2 Participants	32 participants n=32 Participants

PRIMARY outcome

Timeframe: at surgery post approximately 18 weeks of treatment

Population: No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide.

pCR is pathologic complete response defined as ypT0/isN0 on pathology report

Outcome measures

Outcome measures
Measure	Experimental: Optimal- 18 Weeks n=25 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC n=3 Participants 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Optimal With AC Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal no AC n=2 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Percent of Patients Who Achieve a pCR	19 Participants	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From start of neo-adjuvant treatment through approximately 18 weeks.

Population: No participants received less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide.

Defined based on CTCAE version 4: 1. Neutropenia (grade\>2) 2. Thrombocytopenia (grade \>2) 3. Anemia (grade \>2) 4. Diarrhea (any grade, grade \>3) 5. Neuropathy (any grade, grade 2, grade \>3) 6. Vomiting (any grade, grade \>3)

Outcome measures

Outcome measures
Measure	Experimental: Optimal- 18 Weeks n=25 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC n=3 Participants 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Optimal With AC Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal no AC n=2 Participants 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. Diarrhea	23 Participants	3 Participants	—	2 Participants
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. Neuropathy	5 Participants	0 Participants	—	0 Participants
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. Vomiting	5 Participants	1 Participants	—	0 Participants
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. ANC	19 Participants	3 Participants	—	2 Participants
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. Thrombocytopenia	2 Participants	2 Participants	—	0 Participants
Number of of Patients Who Develop Major Toxicities as Defined in Protocol. Anemia	20 Participants	3 Participants	—	2 Participants

Adverse Events

Experimental: Optimal- 18 Weeks

Serious events: 5 serious events

Other events: 25 other events

Deaths: 1 deaths

Experimental: Sub-optimal With AC

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Experimental: Sub-optimal no AC

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Brown University Oncology Research Group

BrUOG

Phone: 4018633000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Experimental: Optimal- 18 Weeks n=25 participants at risk 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC n=3 participants at risk 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Sub-optimal no AC n=2 participants at risk 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Cardiac disorders Atrial fibrillation	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
General disorders Back pain	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Renal and urinary disorders Renal calculi	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
General disorders Dehydration	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Gastrointestinal disorders Enterocolitis	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Cellulitis	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
General disorders Flank pain	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Urinary tract infection	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Sepsis	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Blood and lymphatic system disorders Anemia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Investigations Alanine aminotransferase increased	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Gastrointestinal disorders Salmonella infection	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Skin infection	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Kidney infection	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Gastrointestinal disorders Typhitis	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Investigations Neutropenia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Breast infection	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Reproductive system and breast disorders Breast pain	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
General disorders Progression of disease	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.

Measure	Experimental: Optimal- 18 Weeks n=25 participants at risk 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.	Experimental: Sub-optimal With AC n=3 participants at risk 12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.	Experimental: Sub-optimal no AC n=2 participants at risk 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.
Investigations Neutrophil count increase	92.0% 23/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	66.7% 2/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	100.0% 2/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Investigations Thrombocytopenia	12.0% 3/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	66.7% 2/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Blood and lymphatic system disorders Anemia	88.0% 22/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	66.7% 2/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Gastrointestinal disorders Diarrhea	92.0% 23/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	100.0% 3/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Nervous system disorders Neuropathy	24.0% 6/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Gastrointestinal disorders Vomiting	40.0% 10/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Investigations Alanine aminotransferase increased	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Investigations White blood cell count decreased	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	33.3% 1/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
General disorders Fever	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Cardiac disorders Sinus tachycardia	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Vascular disorders Hypotension	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	50.0% 1/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Infusion related reaction	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Immune system disorders Anaphylaxis	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.
Infections and infestations Upper respiratory infection	4.0% 1/25 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/3 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.	0.00% 0/2 • Adverse events were collected from the time a signed and dated ICF is obtained until 3 months post-operative, or until the subject withdrew consent from study participation, whichever occurs first.