Trial Outcomes & Findings for Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Small Cell Lung Cancer Patients (NCT NCT04902885)

NCT ID: NCT04902885

Last Updated: 2024-07-10

Results Overview

AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 95 participants
• Primary outcome timeframe: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle
• Results posted on: 2024-07-10

Participant Flow

For Part 1, participants were recruited based on physician referral at 4 academic medical centers ，and the first participant was enrolled on May 25, 2021 and the last participant was enrolled in July 20 2021. For Part 2, participants were recruited based on physician referral at 20 academic medical centers ，and the first participant was enrolled in August 20, 2021 and the last participant was enrolled in December 1 2021.

For Part 1, of 14 enrolled participants, 12 met inclusion criteria and were treated with trilaicilib plus chemotherapy. For Part 2, of 105 enrolled participants, 83 met inclusion criteria and were randomized to treatment.

Participant milestones

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group 12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m\^2) plus chemotherapy. Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first. Carboplatin - administered on Day 1 of each 21-day cycle at a target AUC of 5 (maximum dose 750 mg calculated according to Calvert formula) over 30 min by intravenous infusion; etoposide - administered on Days 1, 2, and 3 of each 21-day cycle at 100 mg/m\^2 over 60 min by intravenous infusion; topotecan - administered on Days 1-5 of each 21-day cycle at 1.25 mg/m\^2 over 30 min by intravenous infusion.	Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group 41 patients received trilaciclib(240mg/m\^2) plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first. Carboplatin - administered on Day 1 of each 21-day cycle at a target AUC of 5 (maximum dose 750 mg calculated according to Calvert formula) over 30 min by intravenous infusion; etoposide - administered on Days 1, 2, and 3 of each 21-day cycle at 100 mg/m\^2 over 60 min by intravenous infusion; topotecan - administered on Days 1-5 of each 21-day cycle at 1.25 mg/m\^2 over 30 min by intravenous infusion.	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first. Carboplatin - administered on Day 1 of each 21-day cycle at a target AUC of 5 (maximum dose 750 mg calculated according to Calvert formula) over 30 min by intravenous infusion; etoposide - administered on Days 1, 2, and 3 of each 21-day cycle at 100 mg/m\^2 over 60 min by intravenous infusion; topotecan - administered on Days 1-5 of each 21-day cycle at 1.25 mg/m\^2 over 30 min by intravenous infusion.
Overall Study STARTED	12	41	42
Overall Study COMPLETED	12	41	42
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Small Cell Lung Cancer Patients

Baseline characteristics by cohort

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group n=12 Participants 12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m\^2) plus chemotherapy. Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group n=41 Participants 41 patients received trilaciclib(240mg/m\^2) plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Total n=95 Participants Total of all reporting groups
Age, Continuous	61.1 years STANDARD_DEVIATION 7.06 • n=93 Participants	62.0 years STANDARD_DEVIATION 7.78 • n=4 Participants	59.4 years STANDARD_DEVIATION 8.71 • n=27 Participants	60.7 years STANDARD_DEVIATION 8.13 • n=483 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	33 Participants n=4 Participants	35 Participants n=27 Participants	77 Participants n=483 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	8 Participants n=4 Participants	7 Participants n=27 Participants	18 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	12 Participants n=93 Participants	41 Participants n=4 Participants	42 Participants n=27 Participants	95 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Region of Enrollment China	12 participants n=93 Participants	41 participants n=4 Participants	42 participants n=27 Participants	95 participants n=483 Participants
Brain metastases at baseline	5 participants n=93 Participants	13 participants n=4 Participants	16 participants n=27 Participants	34 participants n=483 Participants

PRIMARY outcome

Timeframe: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle

Population: PK Analysis Set (PKS): All patients who received at least one dose of the study drug and had at least one valid concentration data of the tested components after drug administration. Pharmacokinetic analyses will be based on the PKS set.

AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=6 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=6 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity(AUC0-inf) for Part 1 Day 1 Cycle 1	2200 h*ng/mL Geometric Coefficient of Variation 14.5	2598 h*ng/mL Geometric Coefficient of Variation 23.5	—
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity(AUC0-inf) for Part 1 first line: Day 3 Cycle 1 Second or third line: Day 5 Cycle 1	2878 h*ng/mL Geometric Coefficient of Variation 38.6	2675 h*ng/mL Geometric Coefficient of Variation 22.0	—

PRIMARY outcome

Timeframe: At the end of Cycle 1 (each cycle is 21 days)

Population: The FAS included all enrolled patients who received at least one dose of study drug according to the intention-to-treat (ITT) principle.

DSN in Cycle 1 was defined as the number of days from the date of the first ANC value < 0.5 x 10^9/L in Cycle 1 to the date of the first ANC value ≥ 0.5 x 10^9/L. The date of the first ANC value ≥ 0.5 x 10^9/L should meet the following requirements: (1) occurred after the ANC value was < 0.5 x 10^9/L, and (2) there were no other ANC values < 0.5 x 10^9/L between this date and the end of Cycle 1 (otherwise, if this patient entered Cycle 2, it was counted as Day 1 of Cycle 2). DSN in Cycle 1 was scored as 0 if the patient did not experience any SN during Cycle 1.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Duration of Severe Neutropenia in Cycle 1 (DSN)	0.7 Days Standard Deviation 2.31	0 Days Standard Deviation 1.7	2 Days Standard Deviation 3.0

PRIMARY outcome

Timeframe: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle

Population: PK Analysis Set (PKS): All patients who received at least one dose of the study drug and had at least one valid concentration data of the tested components after drug administration. Pharmacokinetic analyses will be based on the PKS set.

Cmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was below the limit of quantification (BLQ) was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=6 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=6 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Maximum Observed Plasma Concentration(Cmax) of Trilaciclib for Part 1 Day 1 Cycle 1	1007 ng/mL Geometric Coefficient of Variation 18.8	918 ng/mL Geometric Coefficient of Variation 46.7	—
Maximum Observed Plasma Concentration(Cmax) of Trilaciclib for Part 1 First line: Day 3 Cycle 1 Second or third line: Day 5 Cycle 1	893 ng/mL Geometric Coefficient of Variation 36.2	776 ng/mL Geometric Coefficient of Variation 29.9	—

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all enrolled patients who received at least one dose of study drug according to the intention-to-treat (ITT) principle.

Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Severe Neutropenia (SN)	2 Participants	4 Participants	20 Participants

SECONDARY outcome

Timeframe: From week 5 to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least one dose of study drug according to the intention-to-treat (ITT) principle.

The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Red Blood Cell Transfusion (on/After Week 5)	0 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Administration of G-CSF was collected with concomitant medications, which were coded using World Health Organization Drug Dictionary (WHO-DD) . A cycle where G-CSF was administered concurrently was identified by comparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Granulocyte Colony Stimulating Factor (G-CSF) Use Rate	4 Participants	28 Participants	29 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible).

Event rate per week， calculated as the total number of events divided by duration of in weeks.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Composite Endpoints-major Hematologic AEs (Anyone of the Followings): All-cause Hospitalization; All-cause Dose Reductions; Febrile Neutropenia; SN Prolongation (Lasting > 5 Days); Red Blood Cell (RBC) Transfusions Were Performed on/After Week 5.	0.033 events per week	0.040 events per week	0.077 events per week

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Occurrence of Grade 3 and 4 hematological toxicities was defined according to CTCAE 5.0 during the treatment period.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Grade 3 and 4 Hematological Toxicities	6 Participants	24 Participants	38 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Administration of ESA was collected with concomitant medications, which were coded using WHO-DD . A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Erythropoiesis Stimulating Agent (ESA) Use Rate	1 Participants	6 Participants	8 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Administration of interleukin-11 was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where interleukin-11 was administered concurrently was identified by comparing the start and stop dates of each administration of interleukin-11 to the start of cycle and end of cycle. The occurrence of interleukin-11 administration was at least 1 cycle with interleukin-11 administration during the treatment period.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Recombinant Human Interleukin-11 Use Rate	2 Participants	12 Participants	11 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Administration of TPO was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where TPO was administered concurrently was identified by comparing the start and stop dates of each administration of TPO to the start of cycle and end of cycle. The occurrence of TPO administration was at least 1 cycle with TPO administration during the treatment period.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Thrombopoietin (TPO) Use Rate	4 Participants	10 Participants	10 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Administration of intravenous or oral antibiotic was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where intravenous or oral antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of intravenous or oral antibiotic to the start of cycle and end of cycle. The occurrence of intravenous or oral antibiotic administration was at least 1 cycle with intravenous or oral antibiotic administration during the treatment period.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Intravenous or Oral Antibiotic Administration	3 Participants	11 Participants	13 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the Medical Dictionary for Regulatory Activities (MedDRA) system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Infectious Serious Adverse Events	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A lung infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Lung Infection SAEs	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

Each febrile neutropenia event (as defined by Common Terminology Criteria for Adverse Events [CTCAE]) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Febrile Neutropenia	1 Participants	1 Participants	7 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Population: The FAS included all randomized patients who received at least 1 dose of study drug according to the intention-to-treat (ITT) principle.

The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=12 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=41 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Occurrence of Platelet Transfusion	0 Participants	3 Participants	4 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 18 months

Population: Response Evaluable Analysis Set (RES): all patients who took at least one dose of study drug, had measurable disease at baseline, and completed at least one post-treatment tumor imaging assessment. This analysis set was used for the analysis of anti-tumor efficacy endpoints related to tumor RECIST1.1 assessment. efficacy endpoints related to tumor RECIST1.1 assessment.

ORR was performed based on the Response Evaluation Analysis Set (RES). Based on the assessments at each visit, the number and percentage of patients with best response of CR, PR, SD, PD and NE will be summarized by treatment group when CR/PR confirmation is not required and CR/PR confirmation is required, respectively . In particular, SD BOR requires at least 35 days or more after enrollment.ORR was calculated based on the number of patients with best response of CR or PR.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=9 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=38 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=38 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Objective Tumor Response Rate (ORR)	2 Participants	17 Participants	15 Participants

SECONDARY outcome

Timeframe: From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 18 months

Population: Response Evaluable Analysis Set (RES): all patients who took at least one dose of study drug, had measurable disease at baseline, and completed at least one post-treatment tumor imaging assessment. This analysis set was used for the analysis of anti-tumor efficacy endpoints related to tumor RECIST1.1 assessment. efficacy endpoints related to tumor RECIST1.1 assessment.

DCR was performed based on the Response Evaluation Analysis Set (RES). Based on the assessments at each visit, the number and percentage of patients with best response of CR, PR, SD, PD and NE will be summarized by treatment group when CR/PR confirmation is not required and CR/PR confirmation is required, respectively . In particular, SD BOR requires at least 35 days or more after enrollment. DCR was calculated based on the number of patients with best response of CR PR or SD.

Outcome measures

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, First Line ES-SCLC n=9 Participants Trilaciclib 240 mg/m\^2 in patients with first line ES-SCLC receiving carboplatin plus etoposide chemotherapy	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Second or Third Line ES-SCLC n=38 Participants Trilaciclib 240 mg/m\^2 in patients in patients with second or third line ES-SCLC receiving topotecan chemotherapy	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=38 Participants 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Disease Control Rate (DCR)	8 Participants	32 Participants	31 Participants

Adverse Events

Part I ( Safety run-in and PK Evaluation); Trilaciclib Group

Serious events: 4 serious events

Other events: 12 other events

Deaths: 6 deaths

Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group

Serious events: 12 serious events

Other events: 41 other events

Deaths: 22 deaths

Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group

Serious events: 15 serious events

Other events: 42 other events

Deaths: 28 deaths

Serious adverse events

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group n=12 participants at risk 12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m\^2) plus chemotherapy. Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group n=41 participants at risk 41 patients received trilaciclib(240mg/m\^2) plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 participants at risk 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Investigations Neutrophil count decreased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Platelet count decreased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	12.2% 5/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.3% 6/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Alanine aminotransferase increased	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Aspartate aminotransferase increased	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Blood and lymphatic system disorders Anaemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Pyrexia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Oxygen saturation decreased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Cardiac disorders acute cardiac failure	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypochloraemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Infections and infestations Pneumonia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Hepatobiliary disorders Cholelithiasis	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Nervous system disorders Cerebral infarction	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Death	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Disease progression	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations White blood cell count decreased	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months

Other adverse events

Measure	Part I ( Safety run-in and PK Evaluation); Trilaciclib Group n=12 participants at risk 12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m\^2) plus chemotherapy. Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group n=41 participants at risk 41 patients received trilaciclib(240mg/m\^2) plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of Trilaciclib combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received Trilaciclib combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.	Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group n=42 participants at risk 42 patients received placebo plus chemotherapy Patients with first line ES-SCLC received up to 6 cycles of placebo combined with carboplatin and etoposide or continued treatment until disease progression, intolerability, withdrawal of consent, or investigator termination, whichever came first; patients with second or third line ES-SCLC received placebo combined with topotecan until disease progression, intolerability, withdrawal of consent, or investigator termination of treatment, whichever came first.
Investigations Neutrophil count decreased	58.3% 7/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	80.5% 33/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	95.2% 40/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Platelet count decreased	50.0% 6/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	68.3% 28/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	81.0% 34/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations White blood cell count decreased	58.3% 7/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	78.0% 32/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	100.0% 42/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Alanine aminotransferase increased	41.7% 5/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	26.8% 11/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	28.6% 12/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Aspartate aminotransferase increased	33.3% 4/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	19.5% 8/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	23.8% 10/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Gamma-glutamyltransferase increased	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	29.3% 12/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	23.8% 10/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood alkaline phosphatase increased	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	17.1% 7/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Lymphocyte count decreased	33.3% 4/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	19.5% 8/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	26.2% 11/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood bilirubin increased	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.3% 6/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood lactate dehydrogenase increased	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.8% 4/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Gastrointestinal disorders Nausea	41.7% 5/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	31.7% 13/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	33.3% 14/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Gastrointestinal disorders Constipation	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	31.7% 13/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	42.9% 18/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Gastrointestinal disorders Vomiting	33.3% 4/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	12.2% 5/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	19.0% 8/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Blood and lymphatic system disorders Anaemia	66.7% 8/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	68.3% 28/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	83.3% 35/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Blood and lymphatic system disorders Febrile neutropenia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.5% 4/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hyperuricaemia	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	12.2% 5/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.5% 4/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hyponatraemia	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	19.5% 8/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	26.2% 11/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders decreased appetite	41.7% 5/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.6% 6/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	31.0% 13/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypocalcaemia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	12.2% 5/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.5% 4/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypertriglyceridaemia	58.3% 7/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	29.3% 12/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	21.4% 9/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.8% 4/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypoalbuminaemia	25.0% 3/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	19.5% 8/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	28.6% 12/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypercholesterolaemia	25.0% 3/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	17.1% 7/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	23.8% 10/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	17.1% 7/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	28.6% 12/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Weight decreased	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.6% 6/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Asthenia	25.0% 3/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	16.7% 7/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders pyrexia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	17.1% 7/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.3% 6/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Psychiatric disorders Insomnia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	12.2% 5/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Cardiac disorders sinus tachycardia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.8% 4/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Renal and urinary disorders proteinuria	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.8% 4/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Renal and urinary disorders Hematuria	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	9.8% 4/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypokalaemia	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.3% 6/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Respiratory, thoracic and mediastinal disorders cough	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	14.3% 6/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hypochloraemia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders hypomagnesaemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Musculoskeletal and connective tissue disorders back pain	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Renal and urinary disorders Increased serum creatinine	25.0% 3/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Infections and infestations urinary tract infection	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Respiratory, thoracic and mediastinal disorders Chest discomfort	16.7% 2/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Vascular disorders Phlebitis	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders Hyperlipidemia	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.3% 3/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Nervous system disorders Headache	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	11.9% 5/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Metabolism and nutrition disorders hypophosphatemia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Nervous system disorders Dizziness	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Musculoskeletal and connective tissue disorders Pain in limb	0.00% 0/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	7.1% 3/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Alpha hydroxybutyrate dehydrogenase increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Cardiac disorders Tricuspid valve insufficiency	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Cardiac disorders Aortic valve insufficiency	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Cardiac disorders Mitral valve insufficiency	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Weight increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Vascular disorders Venous thrombosis limb	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Urine occult blood positive	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Hypoaesthesia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Injection site pain	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Decreased range of motion	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations White blood cell count increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Fibrin D-dimer increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Musculoskeletal and connective tissue disorders Muscular weakness	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Troponin T increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood urea increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood myoglobin increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood creatine phosphokinase MB increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Blood creatine phosphokinase increased	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.8% 2/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Gastrointestinal disorders Dysphagia	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Oedema peripheral	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
General disorders Chills	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Vascular disorders Embolism	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Investigations Electrocardiogram QT prolonged	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	4.9% 2/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	2.4% 1/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/41 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months	0.00% 0/42 • Adverse events were monitored from the time of informed consent through the end of the safety follow-up period, initiation of new antineoplastic therapy, or withdrawal from the study, whichever came first, acessed up to a maximum of 18 months

Additional Information

Study Director

Jiangsu Simcere Pharmaceutical Co., Ltd.

Phone: 86-025-85566666

Email: simcere@simcere.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place