Trial Outcomes & Findings for Study to Test the Safety and How Radium-223 Dichloride an Alpha Particle-emitting Radioactive Agent Works in Combination With Pembrolizumab an Immune Checkpoint Inhibitor in Patients With Stage IV Non-small Cell Lung Cancer With Bone Metastases (NCT NCT03996473)

Last Updated: 2024-10-10

Results Overview

A treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant, whether or not related to the treatment, arising or worsening after start of study treatment administration until the end of treatment visit (EoT visit, i.e. 30 \[+7\] days after last dose of study treatment). Severities of the TEAEs are summarized overall and by the maximum grade experienced by the participants for any TEAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

8 participants

Primary outcome timeframe

Up to 218 days

Results posted on

2024-10-10

Participant Flow

The study was conducted at multiple centers in 4 countries between 06 March 2020 (first participant first visit) and 30 January 2023 (last participant last visit).

Overall, 10 participants were screened. Of them, 2 participants were screen failures. 8 participants were assigned to study treatment, of which 7 received the study treatment and 1 participant never received the treatment in the Phase 1.

Participant milestones

Participant milestones
Measure	Radium-223 Dichloride + Pembrolizumab Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Treatment Assignment STARTED	8
Treatment Assignment COMPLETED	0
Treatment Assignment NOT COMPLETED	8
Active Follow-up STARTED	1
Active Follow-up COMPLETED	0
Active Follow-up NOT COMPLETED	1
Long-term Follow-up STARTED	6
Long-term Follow-up COMPLETED	1
Long-term Follow-up NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Radium-223 Dichloride + Pembrolizumab Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Treatment Assignment Withdrawal by Subject	1
Treatment Assignment Progressive disease	6
Treatment Assignment Study drug never administered	1
Active Follow-up Death	1
Long-term Follow-up Death	5

Baseline Characteristics

Study to Test the Safety and How Radium-223 Dichloride an Alpha Particle-emitting Radioactive Agent Works in Combination With Pembrolizumab an Immune Checkpoint Inhibitor in Patients With Stage IV Non-small Cell Lung Cancer With Bone Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Age, Continuous	63.6 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 218 days

Population: Safety analysis set (SAF): included all participants who received at least 1 administration of study treatment.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE	7 Participants
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE - Maximum Grade 1	0 Participants
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE - Maximum Grade 2	3 Participants
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE - Maximum Grade 3	2 Participants
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE - Maximum Grade 4	0 Participants
Number of Participants With Treatment-emergent Adverse Events in Phase 1 Any TEAE - Maximum Grade 5	2 Participants

PRIMARY outcome

Timeframe: Up to 278 days

Population: Safety analysis set (SAF): included all participants who received at least 1 administration of study treatment.

A treatment-emergent serious adverse event (TESAE) was any untoward medical occurrence that resulting in death, initial or prolonged inpatient hospitalization, life-threatening, persistent disability/incapacity, congenital anomaly/birth defect, another medical important serious event as judged by the investigator arising or worsening after start of study treatment administration until 90 days after the cessation of study treatment for serious AE (regardless of causality) or until the end of treatment visit (EoT visit, i.e. 30 \[+7\] days after last dose of study treatment) visit if the participant initiated new anti-cancer therapy, whichever was earlier.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Number of Participants With Treatment-emergent Serious Adverse Events in Phase 1	2 Participants

PRIMARY outcome

Timeframe: Within 6 weeks after the first administration of pembrolizumab

Population: DLT analysis set: included all the following participants: a. participants who experienced a DLT during the DLT observation window; b. participants who did not experience a DLT, and who were not dropouts. Dropouts were eligible participants who withdrew during the DLT observation window (within 6 weeks after the first administration of pembrolizumab) for reasons other than experiencing a DLT, and who did not complete both 1 dose of radium-223 dichloride and 2 cycles of pembrolizumab.

Any of following toxicities (exceptions as in protocol) during DLT window was considered a DLT if assessed by investigator to be possibly, probably or definitely related to study treatment: 1.Grade 4 non-hematologic toxicity. 2.Grade 4 hematologic toxicity ≥7 days. 3.Any non-hematologic AE (excl. lab) ≥Grade 3. 4.Any Grade 3 non-hematologic lab value if clinically significant medical intervention required, or the abnormality led to hospitalization, or the abnormality persisted for \>1 week. 5.Grade 3 abnormality in AST, ALT, or bilirubin without liver metastases at screening; The abnormality results in a Drug-induced Liver Injury. 6.Febrile neutropenia Grade 3 or 4. 7.Prolonged delay (\>2 weeks) in initiating Cycle 2 of pembrolizumab due to treatment-related toxicity 8.Any treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1 or 2. 9.Missing \>25% of pembrolizumab doses as a result of drug-related AE(s) during the first cycle. 10.Grade 5 toxicity.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=6 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1	0 Participants

PRIMARY outcome

Timeframe: 0 day as Phase 2 never started due to the early termination of the study

Population: No participant started in Phase 2 part of the study prior to study termination

ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 188 days

Population: Efficacy analysis set (EFF): included all participants who received at least 1 administration of planned dose of any study treatment in Phase 1.

The tumor responses were evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1).

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1 Stable disease (SD)	1 Participants
Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1 Progressive disease (PD)	5 Participants
Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1 Missing	1 Participants

SECONDARY outcome

Timeframe: Up to 188 days

Population: Efficacy analysis set: included all participants who received at least 1 administration of planned dose of any study treatment.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Objective Response Rate (ORR) Per RECIST v1.1 in Phase 1	0 Participants

SECONDARY outcome

Timeframe: Up to 188 days

Population: DoR was not analyzed due to no responder was reported before the study termination among the low number of participants. Tumor responses are reported in a separated outcome measure.

DoR was defined as the time interval from the date of first response (CR or PR) to the date of disease progression or death, whichever comes first. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 188 days

Population: Efficacy analysis set: included all participants who received at least 1 administration of planned dose of any study treatment.

DCR was defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Stable Disease (SD): Steady state of disease. Number of participants with best overall response of CR or PR or SD is reported below while percentage of participants is auto-calculated by ClinicalTrials.gov database.

Outcome measures

Outcome measures
Measure	Radium-223 Dichloride + Pembrolizumab n=7 Participants Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Disease Control Rate (DCR) Per RECIST v1.1 in Phase 1	1 Participants

Timeframe: 0 day as Phase 2 never started due to the early termination of the study

Population: No participant started in Phase 2 part of the study prior to study termination

Outcome measures

Outcome data not reported

Adverse Events

Radium-223 + Pembrolizumab

Serious events: 2 serious events

Other events: 7 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Radium-223 + Pembrolizumab n=7 participants at risk Subjects received radium-223 dichloride every 6 weeks for up to 6 administrations in combination with pembrolizumab every 3 weeks for up to 35 cycles.
Renal and urinary disorders Acute kidney injury	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Musculoskeletal and connective tissue disorders Bone pain	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Rectal haemorrhage	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Respiratory failure	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)

Other adverse events

Other adverse events
Measure	Radium-223 + Pembrolizumab n=7 participants at risk Subjects received radium-223 dichloride every 6 weeks for up to 6 administrations in combination with pembrolizumab every 3 weeks for up to 35 cycles.
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Abdominal pain upper	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Blood and lymphatic system disorders Anaemia	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Musculoskeletal and connective tissue disorders Arthralgia	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Asthenia	42.9% 3/7 • Number of events 3 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Infections and infestations Bronchitis	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Chest pain	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Constipation	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Cough	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Metabolism and nutrition disorders Decreased appetite	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Dyspepsia	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Dysphonia	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Fatigue	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Gastritis	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Metabolism and nutrition disorders Hyponatraemia	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Nausea	42.9% 3/7 • Number of events 3 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Oedema peripheral	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Pain	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Productive cough	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
General disorders Pyrexia	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Respiratory, thoracic and mediastinal disorders Sputum discoloured	14.3% 1/7 • Number of events 1 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Gastrointestinal disorders Vomiting	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)
Investigations Weight decreased	28.6% 2/7 • Number of events 2 • From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the entire study before the last contact (i.e. from signing ICF until the end of follow-up)

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 120 days from the time submitted to the sponsor for review. If a multicenter publication is not published within 18 months after completion of the study and database lock at all research sites or any earlier termination or abandonment of the study, PI shall have the right to publish and present the results.
Publication restrictions are in place

Restriction type: OTHER