Trial Outcomes & Findings for Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer (NCT NCT02779855)

NCT ID: NCT02779855

Last Updated: 2025-12-22

Results Overview

MTD/RP2D of talimogene laherparepvec administered with neoadjuvant paclitaxel- doxorubicin/cyclophosphamide chemotherapy.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE1/PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: Up to 6 months
• Results posted on: 2025-12-22

Participant Flow

Participant milestones

Measure	Talimogene Laherparepvec + Chemotherapy -Phase 1 Dose Level 1 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Talimogene Laherparepvec + Chemotherapy -Phase 1 Dose Level 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 for remaining injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Talimogene Laherparepvec + Chemotherapy -Phase 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase 2 at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Overall Study STARTED	4	6	40
Overall Study COMPLETED	3	6	40
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	Talimogene Laherparepvec + Chemotherapy -Phase 1 Dose Level 1 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Talimogene Laherparepvec + Chemotherapy -Phase 1 Dose Level 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 for remaining injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Talimogene Laherparepvec + Chemotherapy -Phase 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase 2 at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Overall Study Withdrawal by patient prior to treatment	1	0	0

Baseline Characteristics

Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

Baseline characteristics by cohort

Measure	Phase 1 Dose Level 1 n=3 Participants Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 1 Dose Level 2 n=6 Participants Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 for remaining injections. Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 2 n=40 Participants Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=18 Participants	6 Participants n=102 Participants	38 Participants n=30 Participants	47 Participants n=37 Participants
Age, Categorical >=65 years	0 Participants n=18 Participants	0 Participants n=102 Participants	2 Participants n=30 Participants	2 Participants n=37 Participants
Sex: Female, Male Female	3 Participants n=18 Participants	6 Participants n=102 Participants	40 Participants n=30 Participants	49 Participants n=37 Participants
Sex: Female, Male Male	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=18 Participants	2 Participants n=102 Participants	6 Participants n=30 Participants	10 Participants n=37 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=18 Participants	4 Participants n=102 Participants	33 Participants n=30 Participants	38 Participants n=37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=18 Participants	0 Participants n=102 Participants	1 Participants n=30 Participants	1 Participants n=37 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=18 Participants	0 Participants n=102 Participants	1 Participants n=30 Participants	1 Participants n=37 Participants
Race (NIH/OMB) Asian	0 Participants n=18 Participants	0 Participants n=102 Participants	5 Participants n=30 Participants	5 Participants n=37 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Race (NIH/OMB) Black or African American	0 Participants n=18 Participants	2 Participants n=102 Participants	4 Participants n=30 Participants	6 Participants n=37 Participants
Race (NIH/OMB) White	2 Participants n=18 Participants	3 Participants n=102 Participants	27 Participants n=30 Participants	32 Participants n=37 Participants
Race (NIH/OMB) More than one race	0 Participants n=18 Participants	0 Participants n=102 Participants	0 Participants n=30 Participants	0 Participants n=37 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=18 Participants	1 Participants n=102 Participants	3 Participants n=30 Participants	5 Participants n=37 Participants
Region of Enrollment United States	3 participants n=18 Participants	6 participants n=102 Participants	40 participants n=30 Participants	49 participants n=37 Participants

PRIMARY outcome

Timeframe: Up to 6 months

MTD/RP2D of talimogene laherparepvec administered with neoadjuvant paclitaxel- doxorubicin/cyclophosphamide chemotherapy.

Outcome measures

Measure	Talimogene Laherparepvec + Chemotherapy n=9 Participants Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I: Dose Escalation to Determine Maximum Tolerated Dose (MTD). Phase II: Treatment at MTD. Talimogene laherparepvec: Talimogene laherparepvec injection. Phase I: Dose escalation. Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 1 Dose Level 2 Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 PFU for remaining injections. Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 2 Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Phase I: Maximum Tolerated Dose (MTD) / Recommended Phase II Dose (RP2D)	100 million plaque forming units per mL	—	—

PRIMARY outcome

Timeframe: Up to 36 months

Population: All patients evaluable for response per protocol

Perceptage of participants with pCR following study treatment, defined as: Disappearance of histopathologic evidence of malignant cells in breast and axillary lymph nodes.

Outcome measures

Measure	Talimogene Laherparepvec + Chemotherapy n=3 Participants Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I: Dose Escalation to Determine Maximum Tolerated Dose (MTD). Phase II: Treatment at MTD. Talimogene laherparepvec: Talimogene laherparepvec injection. Phase I: Dose escalation. Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 1 Dose Level 2 n=6 Participants Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 2: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 PFU for remaining injections. Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 2 n=37 Participants Phase II: Treatment at Maximum Tolerated Dose (MTD) from Phase I. The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Phase II: Percentage of Participants With Pathologic Complete Response Rate (pCR)	66.7 percentage of participants	50 percentage of participants	43.24 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years follow-up

Percentage of participants who are disease recurrence free at 5 year follow-up.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years follow-up

Percentage of participants who are alive at 5 year follow-up.

Outcome measures

Outcome data not reported

Adverse Events

Phase 1 Dose Level 1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 1 Dose Level 2

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Phase 2

Serious events: 7 serious events

Other events: 39 other events

Deaths: 1 deaths

Serious adverse events

Measure	Phase 1 Dose Level 1 n=3 participants at risk .Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 1 Dose Level 2 n=6 participants at risk .Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 PFU for remaining injections. Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 2 n=40 participants at risk Phase II: Treatment at Maximum Tolerated Dose (MTD) . The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
Cardiac disorders Cardiac arrest	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Fever	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Thromboembolic event	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Periorbital infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Edema limbs	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Lung infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Skin infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Superficial thrombophlebitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Headache	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Syncope	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Blood and lymphatic system disorders Febrile neuropenia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)

Other adverse events

Measure	Phase 1 Dose Level 1 n=3 participants at risk .Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) for all five injections Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 1 Dose Level 2 n=6 participants at risk .Talimogene laherparepvec with Neoadjuvant Paclitaxel Chemotherapy treatment administration on an outpatient basis. Phase I Dose Level 1: 10\^6 PFU (plaque forming units) 1st injection, followed by 10\^8 PFU for remaining injections. Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.	Phase 2 n=40 participants at risk Phase II: Treatment at Maximum Tolerated Dose (MTD) . The MTD dose level is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT). Talimogene laherparepvec: Talimogene laherparepvec injection. Phase II: treatment at MTD Paclitaxel: Paclitaxel chemotherapy infusion. The paclitaxel weekly dose is fixed at 80 mg/m\^2.
General disorders Fatigue	33.3% 1/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 9 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	85.0% 34/40 • Number of events 59 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Fever	100.0% 3/3 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	83.3% 5/6 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	45.0% 18/40 • Number of events 37 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Chills	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	52.5% 21/40 • Number of events 37 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Flu like symptoms	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 15 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Flushing	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Hypotension	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Capillary leak syndrome	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Injection site reaction	33.3% 1/3 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 15 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Infusion related reaction	66.7% 2/3 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	17.5% 7/40 • Number of events 13 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 11 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Edema limbs	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	22.5% 9/40 • Number of events 13 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Non-cardiac chest pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Edema face	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Malaise	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders General disorders and administration site conditions - Other	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Localized edema	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Gait disturbance	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
General disorders Neck edema	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Blood and lymphatic system disorders Anemia	100.0% 3/3 • Number of events 16 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	100.0% 6/6 • Number of events 26 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	87.5% 35/40 • Number of events 102 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Blood and lymphatic system disorders Leukocystosis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 7 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Blood and lymphatic system disorders Febrile neuropenia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Blood and lymphatic system disorders Blood and lymphatic system disorders -Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	100.0% 6/6 • Number of events 12 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	72.5% 29/40 • Number of events 51 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	40.0% 16/40 • Number of events 29 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Constipation	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	37.5% 15/40 • Number of events 18 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Mucositis oral	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	35.0% 14/40 • Number of events 17 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Gastroesophageal reflux disease	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	22.5% 9/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Vomitting	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	22.5% 9/40 • Number of events 13 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	27.5% 11/40 • Number of events 19 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Oral pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	27.5% 11/40 • Number of events 12 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Gastritis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Dry mouth	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Bloating	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Flatulence	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Hemorrhoids	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Cheilitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Dysphagia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	45.0% 18/40 • Number of events 23 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	35.0% 14/40 • Number of events 14 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	32.5% 13/40 • Number of events 14 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Nail discoloration	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 7 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Scalp pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Skin hyperpigmentation	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Nail ridging	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Nail loss	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Periorbital edema	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Photosensitivity	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations White blood cell decreased	33.3% 1/3 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	83.3% 5/6 • Number of events 11 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	47.5% 19/40 • Number of events 43 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Alanine aminotransferase increased	33.3% 1/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 7 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	42.5% 17/40 • Number of events 26 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Neutrophil count decreased	33.3% 1/3 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	83.3% 5/6 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	40.0% 16/40 • Number of events 51 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Alkaline phosphatase increased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	32.5% 13/40 • Number of events 15 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Platelet count decreased	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	17.5% 7/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Weight gain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Weight loss	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Creatinine increased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Lymphocyte count decreased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Ejection fraction decreased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Hemoglobin increased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Investigations Lymphocyte count increased	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Peripheral sensory neuropathy	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 8 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	62.5% 25/40 • Number of events 38 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Headache	66.7% 2/3 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 20/40 • Number of events 33 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Dizziness	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	27.5% 11/40 • Number of events 15 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Dysgeusia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	30.0% 12/40 • Number of events 14 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Cognitive disturbance	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Paresthesia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Nervous system disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Syncope	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Amnesia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Memory impairment	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Nervous system disorders Peripheral motor neuropathy	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	32.5% 13/40 • Number of events 18 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Anorexia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 11 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypernatremia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Metabolism and nutrition disorders Obesity	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Myalgia	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	30.0% 12/40 • Number of events 17 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	30.0% 12/40 • Number of events 19 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	20.0% 8/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 7 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Neck pain	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Upper respiratory infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	32.5% 13/40 • Number of events 16 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Skin infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 15 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Sinusitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Urinary tract infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 12 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Vaginal infection	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Lip infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Paronychia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Lung infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Papulopustular rash	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Infections and infestations - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Mucosal infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Nail infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Periorbital infection	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Infections and infestations Pharyngitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	37.5% 15/40 • Number of events 16 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	50.0% 3/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	22.5% 9/40 • Number of events 12 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	25.0% 10/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	66.7% 4/6 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Hot flashes	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Hypertension	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	17.5% 7/40 • Number of events 10 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Hematoma	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Vascular disorders Thromboembolic event	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Blurred vision	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	17.5% 7/40 • Number of events 9 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Dry eye	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	15.0% 6/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Eye disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Watering eyes	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Conjunctivitis	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Eye pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Floaters	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Eye disorders Papilledema	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Psychiatric disorders Anxiety	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	17.5% 7/40 • Number of events 9 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Psychiatric disorders Depression	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Psychiatric disorders Confusion	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Psychiatric disorders Restlessness	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Breast pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	22.5% 9/40 • Number of events 14 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Irregular menstruation	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Menorrhagia	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Vaginal discharge	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Pelvic pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Vaginal pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Injury, poisoning and procedural complications Bruising	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Reproductive system and breast disorders Vascular access complication	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Injury, poisoning and procedural complications Burn	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Cardiac disorders Palpitations	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	7.5% 3/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Cardiac disorders Sinus bradycardia	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Cardiac disorders Cardiac arrest	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Cardiac disorders Cardiac disorders - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Immune system disorders Allergic reaction	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	12.5% 5/40 • Number of events 5 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Renal and urinary disorders Urinary frequency	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	10.0% 4/40 • Number of events 4 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Renal and urinary disorders Cystitis noninfective	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Renal and urinary disorders Urinary tract pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Renal and urinary disorders Urinary urgency	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Renal and urinary disorders Urine discoloration	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Ear and labyrinth disorders Ear pain	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	16.7% 1/6 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	5.0% 2/40 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Ear and labyrinth disorders Tinnitus	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	33.3% 2/6 • Number of events 3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Ear and labyrinth disorders Vertigo	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Social circumstances Menopause	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/40 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Endocrine disorders Hyperparathyroidism	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	0.00% 0/6 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)	2.5% 1/40 • Number of events 1 • Adverse events collected from on study date to 30 days post last study treatment (3 years, 4.5 months)

Additional Information

Hatem Soliman, MD

Moffitt Cancer Center

Phone: 813-745-4985

Email: hatem.soliman@moffitt.org

Results disclosure agreements

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