Trial Outcomes & Findings for Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin. (NCT NCT03980925)

NCT ID: NCT03980925

Last Updated: 2025-01-13

Results Overview

Percentage of patients alive at 1-year from first dose of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2025-01-13

Participant Flow

Participant milestones

Measure	Nivolumab + Platinum-doublet Chemotherapy 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
Induction Phase STARTED	37
Induction Phase COMPLETED	37
Induction Phase NOT COMPLETED	0
Maintenance Phase STARTED	24
Maintenance Phase COMPLETED	24
Maintenance Phase NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Platinum-doublet Chemotherapy and Nivolumab for the Treatment of Subjects With Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknown (UK) Origin.

Baseline characteristics by cohort

Measure	Combination of Nivolumab and Platinum-doublet Chemotherapy n=37 Participants Patients with unresectable advanced or metastatic G3 (Ki-67 \>20% or mitotic rate \>20 per 10 high-power fields (HPF) neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) or unknown origin treated with a combination of nivolumab and platinum-doublet chemotherapy.
Age, Continuous	61.0 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	34 Participants n=5 Participants
Race/Ethnicity, Customized Latin	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants
Region of Enrollment Spain	37 participants n=5 Participants
ECOG 0	11 Participants n=5 Participants
ECOG 1	22 Participants n=5 Participants
ECOG 2	4 Participants n=5 Participants
Stage at diagnosis I	1 Participants n=5 Participants
Stage at diagnosis III	1 Participants n=5 Participants
Stage at diagnosis IV	35 Participants n=5 Participants
Differentiation Neuroendocrine tumor (NET)	12 Participants n=5 Participants
Differentiation Neuroendocrine carcinoma (NEC)	25 Participants n=5 Participants
Ki-67 21 - 55%	12 Participants n=5 Participants
Ki-67 >55%	25 Participants n=5 Participants
Primary site Esophageal	2 Participants n=5 Participants
Primary site Gastric	6 Participants n=5 Participants
Primary site Pancreatic	14 Participants n=5 Participants
Primary site Colonic	4 Participants n=5 Participants
Primary site Rectal	2 Participants n=5 Participants
Primary site Small intestine	2 Participants n=5 Participants
Primary site Other	2 Participants n=5 Participants
Primary site Unknown	5 Participants n=5 Participants
Metastatic sites number 1	10 Participants n=5 Participants
Metastatic sites number ≥2	27 Participants n=5 Participants
Metastasis sites Liver	31 Participants n=5 Participants
Metastasis sites Lung	9 Participants n=5 Participants
Metastasis sites Lymph nodes	18 Participants n=5 Participants
Metastasis sites Bone	10 Participants n=5 Participants
Previous surgery Yes	6 Participants n=5 Participants
Previous surgery No	30 Participants n=5 Participants
Previous surgery Unknown	1 Participants n=5 Participants
Cromogranin A (CgA) < 2x upper limit normal (ULN)	7 Participants n=5 Participants
Cromogranin A (CgA) ≥ 2x ULN	27 Participants n=5 Participants
Cromogranin A (CgA) Unknown	3 Participants n=5 Participants
Enolase < 2x ULN	13 Participants n=5 Participants
Enolase ≥ 2x ULN	21 Participants n=5 Participants
Enolase Unknown	3 Participants n=5 Participants
Lactate dehydrogenase (LDH) > 2x ULN	9 Participants n=5 Participants
Lactate dehydrogenase (LDH) ≤ 2x ULN	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Percentage of patients alive at 1-year from first dose of treatment.

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Overall Survival Rate at 12 Months

54.1 % of participants Interval 40.2 to 72.8

SECONDARY outcome

Timeframe: Throughout the study period, approximately 24 months

Response to treatment according to RECIST 1.1 criteria or iRECIST 1.1 criteria assessed by computed tomography (CT) scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Overall Response Rate (ORR)

56.8 percentage of participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 24 months

Percentage of patients without progression of disease (PD) calculated from the date of treatment initiation with first-line chemotherapy and nivolumab until the date of first documentation of PD as per RECIST v1.1 or death.

Outcome measures

Measure	Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
Progression-free Survival (PFS) Rate PFS at 12 months	21.6 percentage of participants Interval 11.7 to 39.9
Progression-free Survival (PFS) Rate PFS at 24 months	8.1 percentage of participants Interval 2.7 to 24.0

SECONDARY outcome

Timeframe: 30 months

Length of time between start of treatment and death

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Median Overall Survival

13.9 months Interval 8.3 to 30.0

SECONDARY outcome

Timeframe: 30 months

Assess biochemical response in patients with baseline elevation of enolase and correlate it with clinical outcome.

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Predictive Biomarkers

52.4 Percentage of patients with response

SECONDARY outcome

Timeframe: 30 months

Number and type of adverse events reported throughout the study period according to CTCAE 5.0 criteria.

Outcome measures

Measure	Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Fatigue	60.5 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Neutropenia	55.3 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Nausea	44.7 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Anemia	31.6 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Diarrhea	29 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Vomiting	21.1 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Thrombopenia	21.1 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Anorexia	18.4 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Mucositis	15.8 percentage of participants
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Alopecia	31.6 percentage of participants

SECONDARY outcome

Timeframe: 30 months

Length of time between date of evidenced response and progression of disease or death

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Median Progression-free Survival

5.7 months Interval 5.1 to 9.0

SECONDARY outcome

Timeframe: 30 months

The percentage of patients achieving Complete Response, Partial Response or stable disease (SD)

Outcome measures

Measure

Nivolumab + Platinum-doublet Chemotherapy n=37 Participants 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.

Duration of Response

6.4 month Interval 3.2 to 11.1

Adverse Events

Nivolumab + Platinum-doublet Chemotherapy

Serious events: 18 serious events

Other events: 37 other events

Deaths: 25 deaths

Serious adverse events

Measure	Nivolumab + Platinum-doublet Chemotherapy n=37 participants at risk 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
Gastrointestinal disorders Bowel subocclusion	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Febrile neutropenia	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Platelet count decreased	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Anemia	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Renal and urinary disorders Immune-mediated nephritis	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Infections and infestations Covid-19	10.8% 4/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Injury, poisoning and procedural complications Acute kidney injury	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Renal and urinary disorders Urinary tract obstruction	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders Fever	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Surgical and medical procedures Inguinal hernia	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Infections and infestations Sepsis	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Musculoskeletal and connective tissue disorders Bone pain	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Abdominal pain	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Infections and infestations Bacteremia	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Esophageal hemorrhage	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Esophageal mucositis	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders Multi-organ failure	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Vomiting	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Cognitive disturbance	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Diarrhea	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders General clinical deterioration	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Alanine aminotransferase increased	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Aspartate aminotransferase increased	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Alkaline phosphatase increased	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Blood lactate dehydrogenase increased	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Psychiatric disorders Confusion	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Dysarthria	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Nausea	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Infections and infestations Hepatic infection	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Colitis	2.7% 1/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.

Other adverse events

Measure	Nivolumab + Platinum-doublet Chemotherapy n=37 participants at risk 1. Induction Phase: Nivolumab 360 mg IV plus Carboplatin IV (AUC=5) plus Etoposide 10mg/m2/day on days 1-3D, all every 3 weeks up to 6 cycles followed by Nivolumab 480mg for 24 months or until PD, death or toxicity. Order of administration: Nivolumab, Carboplatin, Etoposide 2. Maintenance Phase Nivolumab 480 mg IV will be administered every 4 weeks (±3 days) for 2 years.
General disorders Fatigue	78.4% 29/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Neutrophil count decreased	56.8% 21/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Nausea	51.4% 19/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Anemia	48.6% 18/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Diarrhea	37.8% 14/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Skin and subcutaneous tissue disorders Alopecia	32.4% 12/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Vomiting	24.3% 9/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Metabolism and nutrition disorders Anorexia	27.0% 10/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Platelet count decreased	24.3% 9/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Gastrointestinal disorders	18.9% 7/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Constipation	24.3% 9/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders Fever	18.9% 7/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Mucositis oral	18.9% 7/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Gastrointestinal disorders Abdominal pain	10.8% 4/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders General disorders and administration site conditions	13.5% 5/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Skin and subcutaneous tissue disorders Pruritus	16.2% 6/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders Febrile neutropenia	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders Edema limbs	10.8% 4/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder	10.8% 4/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Dysgeusia	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Musculoskeletal and connective tissue disorders Arthralgia	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Hepatobiliary disorders Hepatobiliary disorders	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Skin and subcutaneous tissue disorders Rash acneiform	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Blood and lymphatic system disorders White blood cell decreased	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Endocrine disorders Endocrine disorders	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Respiratory, thoracic and mediastinal disorders Cough	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
General disorders Pain	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Endocrine disorders Hypothyroidism	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Alanine aminotransferase increased	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Skin and subcutaneous tissue disorders Dry skin	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Investigations Aspartate aminotransferase increased	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	8.1% 3/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Headache	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Infections and infestations Urinary tract infection	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Endocrine disorders Hyperthyroidism	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Musculoskeletal and connective tissue disorders Back pain	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Dizziness	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Nervous system disorders Peripheral sensory neuropathy	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Metabolism and nutrition disorders Hypomagnesemia	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.
Renal and urinary disorders Renal and urinary disorders	5.4% 2/37 • 30 months Safety data was closely monitored by the contract research organization (CRO) with real time review and assesment of serious adverse events (SAEs) as they were received, and periodic review of all adverse events data for potential new safety signals.

Additional Information

Federico Nepote

MFAR Clinical Research

Phone: +34 93 434 44 12

Email: investigacion@mfar.net

Results disclosure agreements

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