Trial Outcomes & Findings for A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer (NCT NCT03575793)

Last Updated: 2026-01-20

Results Overview

Establish MTD of plinabulin in combination with nivolumab and ipilimumab for patients with recurrent SCLC. MTD reflects the highest dose of plinabulin that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined in accordance to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

39 participants

Primary outcome timeframe

Up to 42 days of first Plinabulin dose

Results posted on

2026-01-20

Participant Flow

Participant milestones

Participant milestones
Measure	Plinabulin 20mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (20mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Overall Study STARTED	8	31
Overall Study COMPLETED	8	28
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Plinabulin 20mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (20mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Overall Study Withdrawal by Subject	0	1
Overall Study Never Treated	0	2

Baseline Characteristics

A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Plinabulin 20mg/m^2 With Nivolumab and Ipilimumab n=8 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (20mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab n=28 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.	Total n=36 Participants Total of all reporting groups
Age, Continuous	56.50 years n=37 Participants	64 years n=44 Participants	60 years n=40 Participants
Sex: Female, Male Female	5 Participants n=37 Participants	12 Participants n=44 Participants	17 Participants n=40 Participants
Sex: Female, Male Male	3 Participants n=37 Participants	16 Participants n=44 Participants	19 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=37 Participants	2 Participants n=44 Participants	2 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=37 Participants	25 Participants n=44 Participants	32 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=37 Participants	1 Participants n=44 Participants	2 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants	1 Participants n=44 Participants	1 Participants n=40 Participants
Race (NIH/OMB) White	8 Participants n=37 Participants	26 Participants n=44 Participants	34 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=44 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	1 Participants n=44 Participants	1 Participants n=40 Participants
Region of Enrollment United States	8 participants n=37 Participants	28 participants n=44 Participants	36 participants n=40 Participants
Brain Metastases Yes	3 Participants n=37 Participants	10 Participants n=44 Participants	13 Participants n=40 Participants
Brain Metastases No	5 Participants n=37 Participants	18 Participants n=44 Participants	23 Participants n=40 Participants
Prior PD-L1 Prior PD-L1 = Yes	3 Participants n=37 Participants	27 Participants n=44 Participants	30 Participants n=40 Participants
Prior PD-L1 Prior PD-L1 = No	5 Participants n=37 Participants	1 Participants n=44 Participants	6 Participants n=40 Participants

PRIMARY outcome

Timeframe: Up to 42 days of first Plinabulin dose

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=16 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Phase I: Maximum Tolerated Dose (MTD)	30 mg/m^2	—

PRIMARY outcome

Timeframe: Up to maximum of 9 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint PFS was defined as all patients with PD-L1 inhibitor resistant recurrent SCLC treated at the plinabulin dose of 30 mg/m\^2 with Nivolumab and Ipilimumab.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease(PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression Free Survival (PFS) is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=27 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Progression-Free Survival (PFS)	1.6 Months Interval 1.2 to 2.7	—

SECONDARY outcome

Timeframe: Up to a maximum of 43 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for Adverse Events was defined as all patients receiving at least one dose of study treatment.

Assess adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=8 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab n=28 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Number of Participants With Adverse Events	8 Participants	28 Participants

SECONDARY outcome

Timeframe: Up to a maximum of 43 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for Adverse Events was defined as all patients receiving at least one dose of study treatment.

Assess Immune-related adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4. irAE's are defined as any treatment-related AE that is inflammatory in nature, consistent with the mechanism of action of immunotherapy and generally medically manageable with topical and/or systemic immunosuppressants.

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=8 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab n=28 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Number of Participants With Immune-related Adverse Events (irAEs)	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to maximum of 9 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Objective Response Rate was defined as all patients with PD-L1 inhibitor resistant recurrent SCLC treated at the plinabulin dose of 30 mg/m\^2. Out of 27 PD-L1 inhibitor resistant patients, only 16 were evaluable for ORR.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST1.1): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Objective Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=16 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Objective Response Rate (ORR)	6 Percentage of participants	—

SECONDARY outcome

Timeframe: Up to maximum of 9 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Clinical Benefit Rate was defined as all patients with PD-L1 inhibitor resistant recurrent SCLC treated at the plinabulin dose of 30 mg/m\^2. Out of 27 PD-L1 inhibitor resistant patients, only 16 were evaluable for CBR.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Clinical Benefit Rate (CBR) = CR+PR+SD per RECIST v1.1.

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=16 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Clinical Benefit Rate	50 Percentage of participants	—

SECONDARY outcome

Timeframe: 6 Months

Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Progression Free Survival at 6 months was defined as all patients with PD-L1 inhibitor resistant recurrent SCLC treated at the plinabulin dose of 30 mg/m\^2 with Nivolumab and Ipilimumab.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause. PFS at 6 months is defined as the percentage of patient who was progression free at 6 months from the initiation of treatment.

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=27 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Progression Free Survival at 6 Months	11 Percentage of participants	—

SECONDARY outcome

Timeframe: Up to a maximum of 45 months

Population: In accordance with the Statistical Analysis Plan, the analysis population for the endpoint Overall Survival was defined as all patients with PD-L1 inhibitor resistant recurrent SCLC treated at the plinabulin dose of 30 mg/m\^2 with Nivolumab and Ipilimumab.

Overall survival is defined as the time from treatment start until death or date of last contact.

Outcome measures

Outcome measures
Measure	Phase I (Dose Escalation): Nivolumab, Ipilimumab and Plinabulin n=27 Participants On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (escalating cohorts, IV). After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur. Plinabulin escalation is as follows: Level -1 : 13.5mg/m\^2 Level 1 (start) : 20mg/m\^2 Level 2 : 30mg/m\^2 Nivolumab: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Plinabulin: Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity originally developed by Nereus Pharmaceuticals, Inc., and now by BeyondSpring Pharmaceuticals, Inc. It belongs to the diketopiperazine class of compounds with a chemical name 2, 5-piperazinedione, 3-\[\[5-(1,1-dimethylethyl)-1H-imidazol-4-yl\[methylene\]-6-(phenylmethylene)-, (3Z,6Z) (trivial name t-butyl-dehydrophenylahistin). Ipilimumab: Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
Overall Survival	4.2 Months Interval 1.9 to 16.9	—

Adverse Events

Plinabulin 20mg/m^2 With Nivolumab and Ipilimumab

Serious events: 4 serious events

Other events: 8 other events

Deaths: 4 deaths

Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab

Serious events: 21 serious events

Other events: 27 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Fauzia Sharmin

Hoosier Cancer Research Network

Phone: 317-921-2050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Plinabulin 20mg/m^2 With Nivolumab and Ipilimumab n=8 participants at risk On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (20mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.	Plinabulin 30mg/m^2 With Nivolumab and Ipilimumab n=28 participants at risk On Day 1 in a 21-day cycle, all patients will receive nivolumab (1 mg/kg, IV), ipilimumab (3 mg/kg, IV) and plinabulin (30mg/m2, IV) for the first 4 cycles. After 4 treatment cycles, ipilimumab will be discontinued and patients will continue treatment with nivolumab 240 mg and plinabulin every 2 weeks (maintenance period) until one of the end of treatment criteria occur.
GASTROINTESTINAL DISORDERS DIARRHEA	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	0.00% 0/28 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS FEVER	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	0.00% 0/28 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
HEPATOBILIARY DISORDERS HEPATOBILIARY DISORDERS - OTHER, SPECIFY	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
VASCULAR DISORDERS HYPOTENSION	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	0.00% 0/28 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
VASCULAR DISORDERS THROMBOEMBOLIC EVENT	12.5% 1/8 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	0.00% 0/28 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RENAL AND URINARY DISORDERS ACUTE KIDNEY INJURY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS ASPIRATION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS BACK PAIN	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
CARDIAC DISORDERS CARDIAC ARREST	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
CARDIAC DISORDERS CARDIAC DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS COLONIC OBSTRUCTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS CONSTIPATION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS DEATH NOS	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
METABOLISM AND NUTRITION DISORDERS DEHYDRATION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS DYSPNEA	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	10.7% 3/28 • Number of events 4 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS EPISTAXIS	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS GASTROINTESTINAL DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS HEMORRHOIDAL HEMORRHAGE	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
HEPATOBILIARY DISORDERS HEPATIC FAILURE	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INFECTIONS AND INFESTATIONS INFECTIONS AND INFESTATIONS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS INFUSION RELATED REACTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INVESTIGATIONS INVESTIGATIONS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INFECTIONS AND INFESTATIONS KIDNEY INFECTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INFECTIONS AND INFESTATIONS LUNG INFECTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	7.1% 2/28 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
METABOLISM AND NUTRITION DISORDERS METABOLISM AND NUTRITION DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	7.1% 2/28 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
NERVOUS SYSTEM DISORDERS NERVOUS SYSTEM DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS NON-CARDIAC CHEST PAIN	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	7.1% 2/28 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS PAIN	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS PANCREATITIS	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS PLEURAL EFFUSION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	10.7% 3/28 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS RESPIRATORY FAILURE	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
CARDIAC DISORDERS RESTRICTIVE CARDIOMYOPATHY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
NERVOUS SYSTEM DISORDERS SEIZURE	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INFECTIONS AND INFESTATIONS SEPSIS	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
CARDIAC DISORDERS SINUS TACHYCARDIA	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS SMALL INTESTINAL OBSTRUCTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS SMALL INTESTINAL PERFORATION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
CARDIAC DISORDERS SUPRAVENTRICULAR TACHYCARDIA	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
INFECTIONS AND INFESTATIONS URINARY TRACT INFECTION	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
VASCULAR DISORDERS VASCULAR DISORDERS - OTHER, SPECIFY	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	3.6% 1/28 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.
GASTROINTESTINAL DISORDERS VOMITING	0.00% 0/8 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.	7.1% 2/28 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 45 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 43 months.