Trial Outcomes & Findings for NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer (NCT NCT03146663)

Last Updated: 2021-02-21

Results Overview

Best overall response to study treatment, as assessed by blinded independent central review according to RECIST v1.1, in the evaluable population of patients who received at least one dose of study treatment and had measurable disease at baseline. Complete Response (CR): disappearance of all target and non-target lesions, normalization of tumor markers, and pathological lymph nodes must have short axis measurements \<10 mm. Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-progressive disease. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. Progressive Disease (PD): ≥20% increase in the sum of measured lesions taking as reference the smallest sum of diameters recorded on study and an absolute increase of ≥5mm.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)

Results posted on

2021-02-21

Participant Flow

A total of 87 patients were screened, of whom 53 patients were randomized and 51 patients received at least one dose of NUC-1031. These 51 patients were included in the full analysis set and the safety analysis set.

Screening details: Patients with histologically-confirmed platinum-resistant high-grade serious, high-grade endometrioid, epithelial cancer of the ovary, fallopian tube or primary peritoneum (here termed 'ovarian cancer'), who had been treated with 3 or more prior chemotherapy regimens were eligible. The Screening visit was to occur within 28 days of Cycle 1 Day 1.

Participant milestones

Participant milestones
Measure	Arm A NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles
Overall Study STARTED	25	28
Overall Study COMPLETED	24	27
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles
Overall Study Did not receive study treatment	1	1

Baseline Characteristics

Time since initial diagnosis for one patient in Arm B (750 mg/m2) was unknown.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=25 Participants NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B n=28 Participants NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Total n=53 Participants Total of all reporting groups
Age, Customized <55 years	6 Participants n=25 Participants	4 Participants n=28 Participants	10 Participants n=53 Participants
Age, Customized 55 - <66 years	6 Participants n=25 Participants	10 Participants n=28 Participants	16 Participants n=53 Participants
Age, Customized 66 - 75 years	9 Participants n=25 Participants	10 Participants n=28 Participants	19 Participants n=53 Participants
Age, Customized >75 years	4 Participants n=25 Participants	4 Participants n=28 Participants	8 Participants n=53 Participants
Sex/Gender, Customized Female	25 Participants n=25 Participants	28 Participants n=28 Participants	53 Participants n=53 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=25 Participants	28 Participants n=28 Participants	52 Participants n=53 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	0 Participants n=28 Participants	0 Participants n=53 Participants
Race/Ethnicity, Customized Asian	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Race/Ethnicity, Customized Black/African American	0 Participants n=25 Participants	2 Participants n=28 Participants	2 Participants n=53 Participants
Race/Ethnicity, Customized White	23 Participants n=25 Participants	26 Participants n=28 Participants	49 Participants n=53 Participants
Race/Ethnicity, Customized Other	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Original diagnosis Ovarian	16 Participants n=25 Participants	20 Participants n=28 Participants	36 Participants n=53 Participants
Original diagnosis Fallopian tube	4 Participants n=25 Participants	2 Participants n=28 Participants	6 Participants n=53 Participants
Original diagnosis Primary peritoneal	3 Participants n=25 Participants	5 Participants n=28 Participants	8 Participants n=53 Participants
Original diagnosis Other	2 Participants n=25 Participants	0 Participants n=28 Participants	2 Participants n=53 Participants
Original diagnosis Not recorded	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Metastatic disease Yes	25 Participants n=25 Participants	26 Participants n=28 Participants	51 Participants n=53 Participants
Metastatic disease No	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Metastatic disease Not recorded	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Time since initial diagnosis	4.3 years n=25 Participants • Time since initial diagnosis for one patient in Arm B (750 mg/m2) was unknown.	5.6 years n=27 Participants • Time since initial diagnosis for one patient in Arm B (750 mg/m2) was unknown.	5.0 years n=52 Participants • Time since initial diagnosis for one patient in Arm B (750 mg/m2) was unknown.
Histology High grade serous	24 Participants n=25 Participants	23 Participants n=28 Participants	47 Participants n=53 Participants
Histology High grade endometroid	1 Participants n=25 Participants	1 Participants n=28 Participants	2 Participants n=53 Participants
Histology Other	0 Participants n=25 Participants	3 Participants n=28 Participants	3 Participants n=53 Participants
Histology Not recorded	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Stage at screening Stage I	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Stage at screening Stage II	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Stage at screening Stage III	8 Participants n=25 Participants	7 Participants n=28 Participants	15 Participants n=53 Participants
Stage at screening Stage IV	13 Participants n=25 Participants	18 Participants n=28 Participants	31 Participants n=53 Participants
Stage at screening Unknown	2 Participants n=25 Participants	2 Participants n=28 Participants	4 Participants n=53 Participants
Stage at screening Not recorded	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Documented deleterious BRCA mutation Yes	4 Participants n=25 Participants	4 Participants n=28 Participants	8 Participants n=53 Participants
Documented deleterious BRCA mutation No	21 Participants n=25 Participants	23 Participants n=28 Participants	44 Participants n=53 Participants
Documented deleterious BRCA mutation Unknown	0 Participants n=25 Participants	1 Participants n=28 Participants	1 Participants n=53 Participants
Eastern Cooperative Oncology Group (ECOG) performance status 0	8 Participants n=25 Participants	12 Participants n=28 Participants	20 Participants n=53 Participants
Eastern Cooperative Oncology Group (ECOG) performance status 1	16 Participants n=25 Participants	16 Participants n=28 Participants	32 Participants n=53 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Unknown	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Comorbidity at baseline Yes	19 Participants n=25 Participants	19 Participants n=28 Participants	38 Participants n=53 Participants
Comorbidity at baseline No	6 Participants n=25 Participants	9 Participants n=28 Participants	15 Participants n=53 Participants
Prior systemic cancer therapy Yes	24 Participants n=25 Participants	27 Participants n=28 Participants	51 Participants n=53 Participants
Prior systemic cancer therapy No	1 Participants n=25 Participants	1 Participants n=28 Participants	2 Participants n=53 Participants
Time to progression after start of most recent chemotherapy <= 1 month	0 Participants n=25 Participants	0 Participants n=28 Participants	0 Participants n=53 Participants
Time to progression after start of most recent chemotherapy >1 to 6 months	14 Participants n=25 Participants	15 Participants n=28 Participants	29 Participants n=53 Participants
Time to progression after start of most recent chemotherapy >6 to 9 months	2 Participants n=25 Participants	1 Participants n=28 Participants	3 Participants n=53 Participants
Time to progression after start of most recent chemotherapy >9 to 12 months	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Time to progression after start of most recent chemotherapy >12 months	1 Participants n=25 Participants	0 Participants n=28 Participants	1 Participants n=53 Participants
Time to progression after start of most recent chemotherapy Missing	7 Participants n=25 Participants	12 Participants n=28 Participants	19 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy <= 1 month	2 Participants n=25 Participants	3 Participants n=28 Participants	5 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy >1 to 3 months	14 Participants n=25 Participants	10 Participants n=28 Participants	24 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy >3 to 6 months	5 Participants n=25 Participants	9 Participants n=28 Participants	14 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy >6 to 9 months	2 Participants n=25 Participants	4 Participants n=28 Participants	6 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy >9 months	1 Participants n=25 Participants	1 Participants n=28 Participants	2 Participants n=53 Participants
Treatment-free interval from completion of most recent chemotherapy Missing	1 Participants n=25 Participants	1 Participants n=28 Participants	2 Participants n=53 Participants
Number of prior lines of therapy	4.5 Therapies n=25 Participants	5.0 Therapies n=28 Participants	4.8 Therapies n=53 Participants
Prior gemcitabine-containing regimen Yes	13 Participants n=25 Participants	17 Participants n=28 Participants	30 Participants n=53 Participants
Prior gemcitabine-containing regimen No	12 Participants n=25 Participants	11 Participants n=28 Participants	23 Participants n=53 Participants

PRIMARY outcome

Timeframe: Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)

Population: Evaluable population are patients who received at least one dose of study treatment and who had measurable disease at baseline.

Outcome measures

Outcome measures
Measure	Arm A n=24 Participants NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B n=26 Participants NUC-1031 750 mg/m2 administered on Days 1, 8 and 15, of 28-day cycles
Best Overall Response Complete response	0 Participants	1 Participants
Best Overall Response Partial response	2 Participants	0 Participants
Best Overall Response Stable disease	8 Participants	8 Participants
Best Overall Response Progressive disease	12 Participants	10 Participants
Best Overall Response Not evaluable	1 Participants	2 Participants
Best Overall Response Missing	1 Participants	5 Participants

POST_HOC outcome

Timeframe: Assessed from date of randomization until disease progression, up to end of the study (approximately 2 years)

Population: Reporting group

Post-hoc analysis of best overall response to study treatment, as assessed by blinded independent central review according to RECIST v1.1, in the per protocol evaluable for response set of patients. Per protocol evaluable for response set is defined as all patients from the Full Analysis Set who had measurable disease at baseline, at least one post-baseline scan and who received a dose of NUC-1031 on all dosing days of Cycle 1.

Outcome measures

Outcome measures
Measure	Arm A n=17 Participants NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B n=5 Participants NUC-1031 750 mg/m2 administered on Days 1, 8 and 15, of 28-day cycles
Best Overall Response (in Evaluable for Response Set) Partial response	2 Participants	0 Participants
Best Overall Response (in Evaluable for Response Set) Stable disease	6 Participants	1 Participants
Best Overall Response (in Evaluable for Response Set) Not evaluable	1 Participants	0 Participants
Best Overall Response (in Evaluable for Response Set) Complete response	0 Participants	1 Participants
Best Overall Response (in Evaluable for Response Set) Progressive disease	8 Participants	3 Participants

Adverse Events

Arm A

Serious events: 8 serious events

Other events: 24 other events

Deaths: 21 deaths

Arm B

Serious events: 10 serious events

Other events: 26 other events

Deaths: 21 deaths

Serious adverse events

Other adverse events

Additional Information

Medical and Scientific Affairs Department

NuCana Plc

Phone: 01313571116

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A n=24 participants at risk NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B n=27 participants at risk NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles
Gastrointestinal disorders Vomiting	8.3% 2/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Constipation	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Diarrhoea	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Nausea	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Small intestinal obstruction	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Infection	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Bacteraemia	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Influenza	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Lower respiratory tract infection	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Lower respiratory tract infection bacterial	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Lung infection	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Respiratory tract infection viral	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Sepsis	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Urinary tract infection	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Pyrexia	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Asthenia	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Vascular disorders Hypotension	0.00% 0/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Vascular disorders Super vena cava syndrome	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Blood and lymphatic system disorders Leukocytosis	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.2% 1/24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)

Measure	Arm A n=24 participants at risk NUC-1031 500 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles	Arm B n=27 participants at risk NUC-1031 750 mg/m2 administered on Days 1, 8, and 15 of 28-day cycles
Gastrointestinal disorders Nausea	66.7% 16/24 • Number of events 18 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	55.6% 15/27 • Number of events 24 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Vomiting	50.0% 12/24 • Number of events 13 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	44.4% 12/27 • Number of events 13 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Diarrhoea	41.7% 10/24 • Number of events 14 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	18.5% 5/27 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Constipation	33.3% 8/24 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	18.5% 5/27 • Number of events 8 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Abdominal Pain	20.8% 5/24 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	18.5% 5/27 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Abdominal distension	16.7% 4/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Ascites	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Fatigue	66.7% 16/24 • Number of events 27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	51.9% 14/27 • Number of events 23 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Pyrexia	29.2% 7/24 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Oedema peripheral	8.3% 2/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	14.8% 4/27 • Number of events 5 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations Alanine aminotransferase increased	29.2% 7/24 • Number of events 10 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	22.2% 6/27 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations Aspartate aminotransferase increased	25.0% 6/24 • Number of events 8 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	18.5% 5/27 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations Neutrophil count decreased	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	22.2% 6/27 • Number of events 14 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations Blood alkaline phosphatase increased	12.5% 3/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations White blood cell count decreased	12.5% 3/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Blood and lymphatic system disorders Anaemia	33.3% 8/24 • Number of events 12 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	22.2% 6/27 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Blood and lymphatic system disorders Thrombocytopaenia	20.8% 5/24 • Number of events 6 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	18.5% 5/27 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Blood and lymphatic system disorders Neutropaenia	25.0% 6/24 • Number of events 12 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	11.1% 3/27 • Number of events 8 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Metabolism and nutrition disorders Decreased appetite	29.2% 7/24 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	22.2% 6/27 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Metabolism and nutrition disorders Dehydration	20.8% 5/24 • Number of events 6 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Metabolism and nutrition disorders Hypomagnesaemia	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	14.8% 4/27 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Metabolism and nutrition disorders Hypoalbuminaemia	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	11.1% 3/27 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	37.5% 9/24 • Number of events 10 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Respiratory, thoracic and mediastinal disorders Cough	25.0% 6/24 • Number of events 6 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Nervous system disorders Dizziness	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	14.8% 4/27 • Number of events 6 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Nervous system disorders Headache	16.7% 4/24 • Number of events 7 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Infections and infestations Urinary tract infection	16.7% 4/24 • Number of events 9 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Musculoskeletal and connective tissue disorders Back pain	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	11.1% 3/27 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Musculoskeletal and connective tissue disorders Muscle spasms	16.7% 4/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Eye disorders Vision blurred	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Renal and urinary disorders Dysuria	12.5% 3/24 • Number of events 4 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Cardiac disorders Tachycardia	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	0.00% 0/27 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Dyspepsia	12.5% 3/24 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Stomatitis	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 3 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Gastrointestinal disorders Abdominal pain lower	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Asthenia	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Chest discomfort	4.2% 1/24 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Influenza like illness	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
General disorders Mucosal inflammation	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Investigations Gamma-glutamyltransferase increased	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Nervous system disorders Dysgeusia	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Nervous system disorders Lethargy	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Nervous system disorders Neuropathy peripheral	4.2% 1/24 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	7.4% 2/27 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Vascular disorders Deep vein thrombosis	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)
Psychiatric disorders Insomnia	8.3% 2/24 • Number of events 2 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)	3.7% 1/27 • Number of events 1 • Date of consent until 30 days after the last dose of study treatment, up to end of the study (approximately 2 years)