Trial Outcomes & Findings for Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Gastrointestinal, Pancreatic, or Colorectal Cancer (NCT NCT03362177)

Participants were enrolled in 55 trial centers in Bulgaria, Greece, Italy, Poland, Portugal, Romania, Spain, Argentina, Brazil, Canada, Mexico, Russia, Turkey, and the United States.

Adult participants receiving oxaliplatin-based chemotherapy regimens for the treatment of gastrointestinal, pancreatic, or colorectal adenocarcinoma were enrolled. Participants were randomized in a 2:1 ratio to receive either romiplostim or placebo, respectively. Randomization was stratified by tumor type and baseline platelet count (\<50 x 10\^9/L and ≥ 50 x 10\^9/L).

Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Gastrointestinal, Pancreatic, or Colorectal Cancer

Participants met the criteria of the primary endpoint if there was no thrombocytopenia-induced modification of any myelosuppressive treatment agent in the second and third cycles of the planned on-trial chemotherapy regimen (cycles were up to 3 weeks). A thrombocytopenia-induced modification was defined as any dose reduction, dose delay, dose omission, and/or early chemotherapy treatment discontinuation due to low platelet counts less than 100 x 10\^9/L. The 95% confidence interval (CI) is based on the exact Clopper-Pearson method.

The platelet count nadir from the first on-trial chemotherapy through the end of the treatment period is presented. The least squares (LS) mean platelet count nadirs were estimated using a general linear model which included treatment, stratification factors, and the interaction between treatment and the stratification factors (tumor type and baseline platelet count).

Platelet response was defined as achieving a platelet count of ≥ 100 x 10\^9/L in the absence of platelet transfusions during the preceding 7 days. Participants who did not achieve a response event during the treatment period were censored at their last platelet count assessment up to end of treatment period or at the randomization date if they did not have any post-baseline platelet assessments.

The duration-adjusted adverse event (AE) incidence rate was the number of events per 100 subject-years from the trial day 1 until the date of last dose of investigational product + 30 days, or end of trial, whichever is earlier. It was calculated as: duration-adjusted event rate per 100 subject years (n/Subj-yr) x 100. The duration-adjusted event rate was assessed for Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 2 bleeding events. CTCAE grading for AEs ranges from Grade 1 (mild) to Grade 5 (death related to AE). Grade 2 AEs were moderate.

Overall survival was defined as the time calculated from trial Day 1 to death. Participants who did not died were censored.

Participants who had at least 1 platelet transfusion during the treatment period.

The number of participants who achieved a platelet count ≥ 100 x 10\^9/L at any time after trial Day 1 to Week 4 (7 days after the planned third dose of IP). If a platelet transfusion occurred during the 7 days preceding a platelet count, then that platelet count was not considered as achieving the endpoint even if it is ≥ 100 x 109/L. Participants who had no platelet counts during this period were considered as not achieving achieved a platelet count ≥ 100 x 109/L. For participants who never received IP, the participants are considered as not achieving a platelet count ≥ 100 x 109/L. Weeks with no platelet count measurements (missing data) were considered as not achieving a platelet count ≥ 100 x 109/L.

An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of IP up to 30 days after the end of investigational product or last dose of on-trial chemotherapy (up to 3 cycles), whichever occurs later. Clinically significant changes in laboratory values were considered AEs. A SAE was defined as any untoward medical occurrence that, met at least 1 ofthe following criteria: resulted in death (fatal), immediately life-threatening,required in-patient hospitalization or prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity or was a congenitalanomaly/birth defect.

Blood samples were collected from all participants for the measurement of anti-romiplostim and anti-TPO binding antibodies. Participants were tested for the presence of anti-romiplostim and anti-TPO antibodies at baseline (pre-existing antibody) and post-baseline (developed antibody). Samples testing positive for binding antibodies were also be tested for neutralizing antibodies.

Events were identified using narrow search of pre-defined list of preferred terms for myelodysplastic syndromes (SMQ). Secondary malignancies included progression from myelodysplastic syndrome to acute myeloid leukemia (AML).