Trial Outcomes & Findings for Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer (NCT NCT02883062)

Last Updated: 2025-10-16

Results Overview

* Pathologic complete response rates will be summarized using contingency tables and compared using Fisher's exact test between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B). * A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

At the time of surgery (3-6 weeks after last dose of neoadjuvant chemotherapy, neoadjuvant chemotherapy will be up to 12 weeks in length)

Results posted on

2025-10-16

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Overall Study STARTED	22	45
Overall Study COMPLETED	16	45
Overall Study NOT COMPLETED	6	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Overall Study Withdrawal by Subject	6	0

Baseline Characteristics

Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) n=22 Participants Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) n=45 Participants Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Total n=67 Participants Total of all reporting groups
Age, Continuous	54 years n=5 Participants	49 years n=7 Participants	52 years n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	45 Participants n=7 Participants	67 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants	42 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	27 Participants n=7 Participants	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	45 participants n=7 Participants	67 participants n=5 Participants
Menopausal status Premenopausal	5 Participants n=5 Participants	20 Participants n=7 Participants	25 Participants n=5 Participants
Menopausal status Postmenopausal	14 Participants n=5 Participants	24 Participants n=7 Participants	38 Participants n=5 Participants
Menopausal status Unknown	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Eastern Cooperative Group (ECOG) Performance Status 0	21 Participants n=5 Participants	41 Participants n=7 Participants	62 Participants n=5 Participants
Eastern Cooperative Group (ECOG) Performance Status 1	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Clinical Stage Clinical Stage II	14 Participants n=5 Participants	31 Participants n=7 Participants	45 Participants n=5 Participants
Clinical Stage Clinical Stage III	8 Participants n=5 Participants	14 Participants n=7 Participants	22 Participants n=5 Participants
Nodal Involvement Positive	11 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants
Nodal Involvement Negative	9 Participants n=5 Participants	24 Participants n=7 Participants	33 Participants n=5 Participants
Nodal Involvement Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Germline BRCA status Wild type	13 Participants n=5 Participants	34 Participants n=7 Participants	47 Participants n=5 Participants
Germline BRCA status Mutant	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Germline BRCA status Unknown	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Baseline PD-L1 status Negative	5 Participants n=5 Participants	19 Participants n=7 Participants	24 Participants n=5 Participants
Baseline PD-L1 status Positive	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Baseline PD-L1 status Unknown	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and between days 18-22 following completion of cycle 1 (each cycle is 3 weeks)

Population: 6 participants in Arm A were excluded. 4 of those participants withdrew consent and did not receive treatment. 2 patients did receive treatment but withdrew consent during treatment. This outcome measure is based on a modified intent-to-treat analysis (mITT). The remaining 3 participants in Arm A and 21 participants in Arm B were not evaluable because their tissue could not be evaluated or because they did not have paired samples.

Will be measured by histopathologic assay. The TIL percentage after initiation of therapy will be compared between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B). The post-treatment TIL percentages between two arms will be summarized using descriptive statistics at each time point.

Outcome measures

Outcome measures
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) n=13 Participants Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) n=24 Participants Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Change in Tumor Infiltrating Lymphocyte (TIL) Percentage Baseline	16.7 percentage of TIL Interval 2.5 to 75.0	17.5 percentage of TIL Interval 0.0 to 80.0
Change in Tumor Infiltrating Lymphocyte (TIL) Percentage Days 18-22 following completion of cycle 1	18.3 percentage of TIL Interval 8.3 to 50.0	21.7 percentage of TIL Interval 3.3 to 50.0

PRIMARY outcome

Timeframe: At the time of surgery (3-6 weeks after last dose of neoadjuvant chemotherapy, neoadjuvant chemotherapy will be up to 12 weeks in length)

Outcome measures

Outcome measures
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) n=16 Participants Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) n=45 Participants Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Pathologic Complete Response (pCR) Rate	3 Participants	25 Participants

SECONDARY outcome

Timeframe: From start of treatment of through completion of AE follow-up (median length of follow-up 2.98 months, full range 0.26-6.56 months)

Population: 4 participants in Arm A were excluded. 4 of those participants withdrew consent and did not receive treatment.

Adverse events were classified and graded using CTCAE version 5.

Outcome measures

Outcome measures
Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) n=18 Participants Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) n=45 Participants Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Adrenal insufficiency	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant ALT increase	0 Participants	2 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Anemia	2 Participants	8 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Anorectal infection	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Arthralgia	1 Participants	0 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant AST increase	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Diarrhea	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Gastroesophageal reflux disease	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Glucose intolerance	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Eye inflammation	1 Participants	0 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Hypocalcemia	1 Participants	0 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Hypokalemia	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Hypertension	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Nausea	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Neutropenia	7 Participants	15 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Thrombocytopenia	1 Participants	0 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Rash	2 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Scleral disorder	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Sepsis	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Skin abscess	0 Participants	2 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Syncope	1 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Vomiting	0 Participants	1 Participants
Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant Leukopenia	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to the time of surgery

Potential biomarkers include baseline TIL percentage, baseline PD-L1 expression in the tumor and tumor infiltrating immune cells, baseline immune signature, and baseline neoantigen load. Univariate and multivariate logistic regression models will be used to evaluate predictive ability of these baseline biomarkers on the response to carboplatin-based chemotherapy in combination with atezolizumab therapy. To take full advantage of such a randomized design, each model will also include the interaction term between treatment assignment and the baseline biomarker. This allows not only to answer the question whether the biomarker is predictive of pCR, but also whether the predictive ability is the same across two arms. The predictive ability will also be summarized using the area under receiver operating characteristic curves (AUC), and the 95% confidence intervals of AUC will be obtained using bootstrap resampling methods.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to the time of surgery

The immune signature and PD-L1 expression in the tumor and tumor-infiltrating immune cells will be evaluated at baseline, after initiation of therapy (day 18-22), and at the time of surgery. The temporal changes of immune signature and PD-L1 expression in each arm will be summarized using contingency tables or descriptive statistics (means, standard deviations, medians, etc.) as appropriate. The differences of temporal change between treatment groups (Arm A versus \[vs.\] Arm B) or their association with clinical outcome (pCR vs. non-pCR) will also be assessed musing mixed model (PD-L1 expression) or generalized linear mixed model (immune signatures).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to the time of surgery

The immune signature and PD-L1 expression in the tumor and tumor-infiltrating immune cells will be evaluated at baseline, after initiation of therapy (day 18-22), and at the time of surgery. The temporal changes of immune signature and PD-L1 expression in each arm will be summarized using contingency tables or descriptive statistics (means, standard deviations, medians, etc.) as appropriate. The differences of temporal change between treatment groups (Arm A vs. Arm B) or their association with clinical outcome (pCR vs. non-pCR) will also be assessed musing mixed model (PD-L1 expression) or generalized linear mixed model (immune signatures).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 1 year

The frequency and function of neoantigen-specific T cell across the two arms in the peripheral blood at each time point will be summarized using tools for high throughput analysis. The differences of temporal changes in neoantigen-specific T cell between treatment groups (Arm A versus Arm B) or their association with clinical outcome (pCR vs. non-pCR) will also be assessed using mixed models, followed by ad-hoc adjustment for multiple comparisons.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Time from randomization to death due to any causes, assessed up to 1 year

The distribution of OS in the two treatment arms will be described using Kaplan-Meier product limit methods and compared by log-rank tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Time from randomization to disease recurrence or death due to any causes, assessed up to 1 year

The distribution of DFS in the two treatment arms will be described using Kaplan-Meier product limit methods and compared by log-rank tests.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy)

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery)

Serious events: 10 serious events

Other events: 45 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. William Gillanders

Washington University School of Medicine

Phone: 314-747-0072

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A (Carboplatin, Paclitaxel, Mastectomy, Lumpectomy) n=18 participants at risk Patients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.	Arm B (Atezolizumab, Carboplatin, Paclitaxel, Breast Surgery) n=45 participants at risk Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Blood and lymphatic system disorders Anemia	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Cardiac disorders Ventricular tachycardia	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Eye disorders Eye inflammation	5.6% 1/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Gastrointestinal disorders Nausea	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Gastrointestinal disorders Vomiting	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
General disorders Fatigue	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
General disorders Fever	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Infections and infestations Anorectal infection	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Infections and infestations Sepsis	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Injury, poisoning and procedural complications Fracture	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Investigations ALT increase	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Investigations AST increase	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Investigations Neutropenia	5.6% 1/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	4.4% 2/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Metabolism and nutrition disorders Hypocalcemia	5.6% 1/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Nervous system disorders Syncope	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	4.4% 2/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/18 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.	2.2% 1/45 • -Median length of follow-up was 2.98 months (full range 0.26-6.56 months). -Median length of follow-up for adverse events was 15.70 months (full range 0.03-19.61 months). -All-cause mortality was followed for all patients even if there were major protocol treatment deviations or if they did not start treatment.