Trial Outcomes & Findings for Phase I Study Compound 451238 and Radiotherapy in Soft-tissue Sarcoma (NCT NCT03602833)

Last Updated: 2026-03-02

Results Overview

To assess the safety and tolerability of combining radiotherapy with compound 451238(avelumab) as evidenced by the rate of occurrence of dose limiting toxicities assessed using CTCAE v4.0. .

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Dose limiting toxicity was assessed from first dose of avelumab in week 1, then weekly until and including week 7 and every other week thereafter until and including the 7th dose of avelumab at week 13

Results posted on

2026-03-02

Participant Flow

Participant milestones

Participant milestones
Measure	All Patients Treated With Compound 451238 All patients who received at least one dose of compound 451238 (avelumab)
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I Study Compound 451238 and Radiotherapy in Soft-tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Patients Treated With Compound 451238 n=12 Participants All patients who received at least one dose of compound 451238 (avelumab), at the dose level of 10mg/kg (note that one single fixed dose level was defined for this study)
Age, Continuous	57.5 years n=41 Participants
Sex: Female, Male Female	7 Participants n=41 Participants
Sex: Female, Male Male	5 Participants n=41 Participants
Race/Ethnicity, Customized Caucasian	12 Participants n=41 Participants
Region of Enrollment United Kingdom	12 participants n=41 Participants

PRIMARY outcome

Timeframe: Dose limiting toxicity was assessed from first dose of avelumab in week 1, then weekly until and including week 7 and every other week thereafter until and including the 7th dose of avelumab at week 13

Population: All patients with at least one dose of avelumab and one fraction of radiotherapy

To assess the safety and tolerability of combining radiotherapy with compound 451238(avelumab) as evidenced by the rate of occurrence of dose limiting toxicities assessed using CTCAE v4.0. .

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=12 Participants All patients who received at least one dose of compound 451238 (avelumab)
Count of Patients With Dose Limiting Toxicity	0 Participants

SECONDARY outcome

Timeframe: 3 months from end of radiotherapy

Local control (LC) at 3 months from end of radiotherapy, calculated using Kaplan-Meier methods with patients without documented local progression censored at death or last known follow-up for surviving patients

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=12 Participants All patients who received at least one dose of compound 451238 (avelumab)
Evaluate Local Control (LC)	50 percentage of participants Interval 21.0 to 74.0

SECONDARY outcome

Timeframe: 1 Year

Population: All patients with at least one dose of study drug and one fraction of radiotherapy

Progression free survival (PFS) at 6 months and 1 year from start of avelumab, calculated using Kaplan-Meier methods

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=12 Participants All patients who received at least one dose of compound 451238 (avelumab)
Progression Free Survival (PFS) 6 month PFS	50 percentage of participants Interval 21.0 to 74.0
Progression Free Survival (PFS) 12 month PFS	8 percentage of participants Interval 1.0 to 31.0

SECONDARY outcome

Timeframe: Start of treatment to 2 years

Population: All patients treated with at least one dose of study drug and one fraction of radiotherapy

Overall survival (OS) at 1 and 2 years from start of avelumab, calculated using Kaplan-Meier methods

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=12 Participants All patients who received at least one dose of compound 451238 (avelumab)
Overall Survival OS at one year	67 percentage of participants Interval 34.0 to 86.0
Overall Survival OS at two years	49 percentage of participants Interval 19.0 to 73.0

SECONDARY outcome

Timeframe: 11 weeks

Population: All patients who have received at least one dose of study drug and one fraction of radiotherapy, and who have completed at least one assessment for weekly radiation toxicity

Patients are assessed weekly from start of treatment up to and including week 11, for targeted toxicities (skin, myelitis, oesophagus, pneumonitis, cardiac) and any other organ toxicities, graded using the RTOG radiation toxicity grading system, which ranges from 0 (no symptoms) through 1(mild symptoms not requiring intervention), 2( moderate symptoms that may require intervention), 3(severe symptoms requiring more intensive intervention), 4 (life-threatening symptoms requiring urgent intervention), up to a maximum of 5 (death).

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=11 Participants All patients who received at least one dose of compound 451238 (avelumab)
Count of Patients by Worst Grade Acute Toxicity Cardiac toxicity · Max grade 0	11 Participants
Count of Patients by Worst Grade Acute Toxicity Cardiac toxicity · Max grade 1	0 Participants
Count of Patients by Worst Grade Acute Toxicity Cardiac toxicity · Max grade 2	0 Participants
Count of Patients by Worst Grade Acute Toxicity Myelitis · Max grade 0	11 Participants
Count of Patients by Worst Grade Acute Toxicity Myelitis · Max grade 1	0 Participants
Count of Patients by Worst Grade Acute Toxicity Myelitis · Max grade 2	0 Participants
Count of Patients by Worst Grade Acute Toxicity Oesophagus · Max grade 0	9 Participants
Count of Patients by Worst Grade Acute Toxicity Oesophagus · Max grade 1	1 Participants
Count of Patients by Worst Grade Acute Toxicity Oesophagus · Max grade 2	1 Participants
Count of Patients by Worst Grade Acute Toxicity Pneumonitis · Max grade 0	9 Participants
Count of Patients by Worst Grade Acute Toxicity Pneumonitis · Max grade 1	2 Participants
Count of Patients by Worst Grade Acute Toxicity Pneumonitis · Max grade 2	0 Participants
Count of Patients by Worst Grade Acute Toxicity Skin · Max grade 0	6 Participants
Count of Patients by Worst Grade Acute Toxicity Skin · Max grade 1	3 Participants
Count of Patients by Worst Grade Acute Toxicity Skin · Max grade 2	2 Participants
Count of Patients by Worst Grade Acute Toxicity Other (cough, constipation, fatigue) · Max grade 0	8 Participants
Count of Patients by Worst Grade Acute Toxicity Other (cough, constipation, fatigue) · Max grade 1	3 Participants
Count of Patients by Worst Grade Acute Toxicity Other (cough, constipation, fatigue) · Max grade 2	0 Participants

SECONDARY outcome

Timeframe: From 13 weeks from start of treatment until 90 days after the end of treatment

Population: All patients with at least one dose of study drug and one fraction of radiotherapy, who have been assessed at least once for late radiotherapy toxicity

Patients are assessed every two weeks starting at 13 weeks from the start of treatment, for targeted radiotherapy toxicities (skin, myelitis, oesophagus, pneumonitis, cardiac) and any other organ toxicities, graded using the RTOG radiation toxicity grading system, which ranges from 0 (no symptoms) through 1(mild symptoms not requiring intervention), 2( moderate symptoms that may require intervention), 3(severe symptoms requiring more intensive intervention), 4 (life-threatening symptoms requiring urgent intervention), up to a maximum of 5 (death).

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=9 Participants All patients who received at least one dose of compound 451238 (avelumab)
Count of Patients by Worst Grade Late Toxicity Cardiac · Worst grade 0	8 Participants
Count of Patients by Worst Grade Late Toxicity Cardiac · Worst grade 1	1 Participants
Count of Patients by Worst Grade Late Toxicity Cardiac · Worst grade 2	0 Participants
Count of Patients by Worst Grade Late Toxicity Myelitis · Worst grade 0	8 Participants
Count of Patients by Worst Grade Late Toxicity Myelitis · Worst grade 1	1 Participants
Count of Patients by Worst Grade Late Toxicity Myelitis · Worst grade 2	0 Participants
Count of Patients by Worst Grade Late Toxicity Oesophagus · Worst grade 0	8 Participants
Count of Patients by Worst Grade Late Toxicity Oesophagus · Worst grade 1	1 Participants
Count of Patients by Worst Grade Late Toxicity Oesophagus · Worst grade 2	0 Participants
Count of Patients by Worst Grade Late Toxicity Pneumonitis · Worst grade 0	5 Participants
Count of Patients by Worst Grade Late Toxicity Pneumonitis · Worst grade 1	4 Participants
Count of Patients by Worst Grade Late Toxicity Pneumonitis · Worst grade 2	0 Participants
Count of Patients by Worst Grade Late Toxicity Skin · Worst grade 0	6 Participants
Count of Patients by Worst Grade Late Toxicity Skin · Worst grade 1	3 Participants
Count of Patients by Worst Grade Late Toxicity Skin · Worst grade 2	0 Participants
Count of Patients by Worst Grade Late Toxicity Other · Worst grade 0	9 Participants
Count of Patients by Worst Grade Late Toxicity Other · Worst grade 1	0 Participants
Count of Patients by Worst Grade Late Toxicity Other · Worst grade 2	0 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Patients with a positive PD-L1 test - note that as the planned laboratory work to identify PD-L1 scores was not completed due to lack of available funding, no patients can be identified for this planned subgroup analysis and this data can not be collected now or in the future.

Progression free survival (PFS) at 6 months and 1 year from start of avelumab, calculated using Kaplan-Meier methods in the PD-L1 positive subgroup

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Overall survival (OS) at 6 months and 1 year from start of avelumab, calculated using Kaplan-Meier methods in the PD-L1 positive subgroup

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months following first dose of trial treatment

Population: All patients assessed for response in non-target lesions

Count of patients by response in non-target (i.e. not irradiated) lesions on imaging at 3

Outcome measures

Outcome measures
Measure	All Patients Treated With Compound 451238 n=9 Participants All patients who received at least one dose of compound 451238 (avelumab)
Response Rate in Non-target Lesions Neither complete response or progressive disease	4 Participants
Response Rate in Non-target Lesions Progressive disease	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Best response within 6 months from commencing trial treatment

Population: The planned laboratory work to identify exploratory biomarkers was not performed, so no patients have been analysed

Overall response in subgroups of patients classified by expression of various exploratory immunological biomarkers

Outcome measures

Outcome data not reported

Adverse Events

All Patients Treated With Compound 451238

Serious events: 5 serious events

Other events: 12 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	All Patients Treated With Compound 451238 n=12 participants at risk All patients who received at least one dose of compound 451238 (avelumab)
Infections and infestations Device related infection	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Wound infection	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Sepsis	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Viral infection	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Hepatobiliary disorders IMMUNE MEDIATED HEPATITIS	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Nervous system disorders MUSCLE WEAKNESS	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders PNEUMOTHORAX	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations CARDIAC TROPONIN INCREASED	8.3% 1/12 • Number of events 1 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.

Other adverse events

Other adverse events
Measure	All Patients Treated With Compound 451238 n=12 participants at risk All patients who received at least one dose of compound 451238 (avelumab)
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Cardiac disorders Atrial fibrillation	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Cardiac disorders Chest pain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Endocrine disorders Hypothyroidism	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Anal hemorrhage	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Constipation	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Dry mouth	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Esophageal pain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Esophagitis	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Nausea	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Chills	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Fatigue	66.7% 8/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Fever	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Infusion related reaction	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Localised edema	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Non-cardiac chest pain	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Pain	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Hepatobiliary disorders Immune-mediated hepatitis	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Device related infectiom	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Laryngitis	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
General disorders Other	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Sepsis	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Urinary tract infection	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Wound infection	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Infections and infestations Other	50.0% 6/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Alanine aminotransferase increased	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Alkaline phosphatase increased	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Aspartate aminotransferase increased	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Cardiac troponin I increased	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Ejection fraction decreased	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Lymphocyte count decreased	33.3% 4/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Neutrophil count decreased	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations Weight gain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Investigations White blood cell decreased	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Metabolism and nutrition disorders Anorexia	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Metabolism and nutrition disorders Hypercalcemia	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Back pain	41.7% 5/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Chest wall pain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Other	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Nervous system disorders Dizziness	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Nervous system disorders Headache	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Nervous system disorders Parasthesia	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Psychiatric disorders Insomnia	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Renal and urinary disorders Cystitis noninfective	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Renal and urinary disorders Urinary frequency	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Renal and urinary disorders Urinary tract pain	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Reproductive system and breast disorders Genital edema	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Cough	41.7% 5/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 6/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Other	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 2/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Skin and subcutaneous tissue disorders Other	25.0% 3/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Skin and subcutaneous tissue disorders Pruritus	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 4/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Vascular disorders Hypertension	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.
Vascular disorders Thromboembolic event	8.3% 1/12 • Adverse events are assessed weekly from start of study drug up to and including week 7, and then two weekly until death, end of study, or 90 days following the final dose of study drug (whichever occurs first), to a maximum of 21 months. All cause mortality is assessed from start of treatment to 2 years.

Additional Information

Angelie Tirona

The Royal Marsden NHS Foundation Trust

Phone: +44 20 8915 6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place