Trial Outcomes & Findings for A Study for Patients That Have Been Previously Been Treated in Waldenstrom's Macroglobulinemia or Multiple Myeloma (NCT NCT00718419)

Last Updated: 2020-09-03

Results Overview

European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria (RC) used for MM. CR: no serum/urine M protein for 6 weeks (wk), \<5% plasma cells in bone marrow (PCBM), no lytic bone lesions (LBL) size/number increase, no soft tissue plasmacytomas (STPC); PR: met some CR criteria plus maintain for 6 wk ≥50% serum monoclonal paraprotein (SPEP) and PCBM decrease, either decrease of ≥90% or \<200 mg light chain excretion (LCE), ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk, a decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. International Workshop on WM (IWWM) RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% immunoglobulin M (IgM) and adenopathy/organomegaly (A/O) decrease; no new symptoms of WM. MinR: ≥25% to \<50% IgM decrease, no A/O progression; no cytopenias or clinical symptoms of WM.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

Baseline to measured progressive disease up to 40.51 months

Results posted on

2020-09-03

Participant Flow

Participant milestones

Participant milestones
Measure	Multiple Myeloma (MM) Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Overall Study STARTED	14	42
Overall Study Received at Least One Dose of Study Drug	14	42
Overall Study COMPLETED	1	3
Overall Study NOT COMPLETED	13	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Multiple Myeloma (MM) Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Overall Study Adverse Event	2	1
Overall Study Physician Decision	1	6
Overall Study Sponsor decision	0	1
Overall Study Withdrawal by Subject	0	5
Overall Study Progressive Disease	7	25
Overall Study Death Due to Progressive Disease	2	0
Overall Study Death Due to Study Drug Related	0	1
Overall Study Death Due to Adverse Events	1	0

Baseline Characteristics

A Study for Patients That Have Been Previously Been Treated in Waldenstrom's Macroglobulinemia or Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Multiple Myeloma (MM) n=14 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Total n=56 Participants Total of all reporting groups
Age, Continuous	73.28 years STANDARD_DEVIATION 7.51 • n=5 Participants	64.57 years STANDARD_DEVIATION 8.53 • n=7 Participants	66.7 years STANDARD_DEVIATION 9.06 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	35 Participants n=7 Participants	43 Participants n=5 Participants
Race/Ethnicity, Customized African	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	14 Participants n=5 Participants	41 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment France	14 Participants n=5 Participants	5 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United States	0 Participants n=5 Participants	37 Participants n=7 Participants	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to measured progressive disease up to 40.51 months

Population: All participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Multiple Myeloma (MM) n=14 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate)	7.1 percentage of participants	38.1 percentage of participants

SECONDARY outcome

Timeframe: Time of response to time of measured progressive disease up to 38.37 months

Population: All participants who received at least one dose of the study drug and had complete response (CR) or partial response (PR) or minimal response (MR) or minor response (MinR). The numbers of participants censored are 1 (MM) and 13 (WM).

DOR is defined as elapsed time from the first evidence of CR, PR, MR or MinR until date of progression of disease (PD). EBMT RC used for MM. CR: no serum/urine M protein for 6 wk, \<5% PCBM, no LBL size/number increase, no STPC; PR: met some CR criteria plus maintain for 6 wk ≥50% SPEP and PCBM decrease, either decrease of ≥90% or \<200 mg LCE, ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. PD: \>25% increase in SPEP, 24 hour urinary LCE, PCBM, STPC size increase, new bone lesion or STPC. IWWM RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% IgM and A/O decrease; no new WM symptoms. MinR: ≥25% to \<50% IgM decrease, no A/O progression; no cytopenias or clinical of WM symptoms. PD: \>25% IgM increase, progression of clinical findings or symptoms. For participants who had no PD, DOR was censored at their last contact.

Outcome measures

Outcome measures
Measure	Multiple Myeloma (MM) n=1 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=16 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Duration of Response (DOR)	NA months Only 1 participant had response, therefore median and 95% Confidence Interval were not calculable.	NA months Interval 17.87 to Only 3 participants had events, therefore median was not calculated. The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Baseline to measured progressive disease up to 40.51 months

Population: All participants who had at least one dose of the study drug. The numbers of participants censored are 7 (MM) and 33 (WM).

Time to progression is defined as the elapsed time from the date of study enrollment to the date of objectively determined progressive disease (PD). European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria was used for MM. PD: \>25% increase in serum monoclonal paraprotein (SPEP), 24 hour urinary light chain excretion (LCE), plasma cells in bone marrow (PCBM), soft tissue plasmacytomas (STPC) size increase, new bone lesion or STPC. International Workshop on WM (IWWM) Response Criteria was used for WM. PD: \>25% immunoglobulin M (IgM) increase, progression of clinical findings or symptoms. For participants who had no PD, time to PD was censored at their last contact.

Outcome measures

Outcome measures
Measure	Multiple Myeloma (MM) n=14 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Time to Progressive Disease	5.11 months Interval 2.86 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	27.73 months Interval 20.47 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Treatment start to 30 days after discontinuation of study treatment up to 23.40 months

Population: All participants who received at least one dose of the study drug.

Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 23.40 months.

Outcome measures

Outcome measures
Measure	Multiple Myeloma (MM) n=14 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Number of Participants With Adverse Events (Safety and Adverse Events) Serious Adverse Events	4 Participants	9 Participants
Number of Participants With Adverse Events (Safety and Adverse Events) Other Nonserious Adverse Events	12 Participants	42 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Study treatment discontinuation up to 30 days post study treatment discontinuation

Population: All participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	Multiple Myeloma (MM) n=14 Participants Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 Participants Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment	0 Participants	1 Participants

Adverse Events

Multiple Myeloma (MM)

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Waldenstrom's Macroglobulinemia (WM)

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Multiple Myeloma (MM) n=14 participants at risk Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Waldenstrom's Macroglobulinemia (WM) n=42 participants at risk Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Blood and lymphatic system disorders Anaemia	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Cardiac disorders Cardiac failure	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Cardiac disorders Myocardial infarction	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Nausea	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Peritoneal haemorrhage	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Volvulus	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Gastrointestinal disorders Vomiting	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
General disorders Asthenia	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
General disorders Chest pain	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
General disorders General physical health deterioration	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Infections and infestations Abscess	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Infections and infestations Clostridium difficile colitis	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 2 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Infections and infestations Pneumocystis jiroveci pneumonia	7.1% 1/14 • Number of events 2 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Infections and infestations Sepsis	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Infections and infestations Septic shock	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Injury, poisoning and procedural complications Wound	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Metabolism and nutrition disorders Dehydration	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Nervous system disorders Iiird nerve paralysis	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Nervous system disorders Syncope	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Renal and urinary disorders Renal failure acute	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Respiratory, thoracic and mediastinal disorders Bronchopneumopathy	7.1% 1/14 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	0.00% 0/42 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Vascular disorders Thrombophlebitis	0.00% 0/14 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.	2.4% 1/42 • Number of events 1 Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.