Small Cell Lung Cancer
Conditions
Keywords
SCLC, CDK4/6 Inhibitor
Brief summary
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC. The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.
Detailed description
Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2). Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group). The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher. The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report. The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off \[DCO\] for Primary Completion Date \[PCD\] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021). The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.
Interventions
DRUGTrilaciclib
DRUGPlacebo
DRUGTopotecan
Sponsors
G1 Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female subjects aged ≥18 years * Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry * Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy * At least 1 target lesion that is measurable by RECIST, Version 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 * Adequate organ function Key
Exclusion criteria
* Presence of brain metastases requiring immediate treatment with radiation therapy or steroids. * Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure * Known history of stroke or cerebrovascular accident within 6 months prior to enrollment * Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol * Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites * Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment * History of topotecan treatment for SCLC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Severe (Grade 4) Neutropenia in Cycle 1 | Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days) | Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of \<0.5 × 10\^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10\^9/L that met the following criteria: (1) occurred after the ANC value of \<0.5 × 10\^9/L and (2) no other ANC values \<0.5 × 10\^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation. |
| Occurrence of Severe (Grade 4) Neutropenia | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value \<0.5 × 10\^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No. |
| Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days) | The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: * Absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting for ≥ 7 days * ≥ Grade 3 neutropenic infection/febrile neutropenia * Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding * Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10\^9/L and platelet count ≥ 100 × 10\^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT * ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for \> 72 hours) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | The weekly event rate of Major Adverse Hematologic Events (MAHE) events |
| Tumor Response Based on RECIST, Version 1.1 | From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). | The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE. |
| Occurrence of RBC Transfusions | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days). | Percentage of patients requiring a RBC transfusion on/after week 5 |
| Need for Treatment With Hematopoietic Growth Factors | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients requiring G-CSF administration. |
| Chemotherapy Cycles and Modifications Overall | During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). | Average exposure and cycle modifications in chemotherapy (topotecan) |
| Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. | Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28) |
| Duration of Response (DOR) | From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). | The median months and 95% CIs of duration of response. |
| Occurrence of Intravenous (IV) Antibiotic Use | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients requiring systemic/IV antibiotics |
| Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. | Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan |
| Occurrence of Febrile Neutropenia Adverse Events | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients who experience febrile neutropenia adverse events |
| Occurrence of Infection Serious Adverse Events (SAEs) | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations |
| Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ) |
| Dose Reductions in Chemotherapy (Topotecan) | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Overall event rate of dose reductions in chemotherapy (topotecan) |
| Occurrence of Grade 3 and 4 Hematologic Toxicities | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute. |
| Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). |
| Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | The count of patients who received any ESA administration. |
| Chemotherapy Exposure | During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). | Average duration of exposure to chemotherapy (topotecan) in days. |
| Occurrence of Platelet Transfusions | During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). | Percentage of patients requiring a platelet transfusion |
| Progression Free Survival (PFS) | From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days). | Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause. Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival (OS) | From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days). | Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive. |
Countries
Belgium, Bosnia and Herzegovina, Croatia, North Macedonia, Serbia, Slovakia, Slovenia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).
Placebos
Topotecan | 29 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).
Trilaciclib
Topotecan | 30 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).
Trilaciclib
Topotecan | 32 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). | 2 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). | 3 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). | 4 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). | 8 |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). | 7 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.
Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²). | 8 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 24 | 28 | 29 | 0 | 3 | 4 | 8 | 6 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Sponsor Termination of Study | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study completion per Investigator | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 12 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants | 6 Participants | 52 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 20 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 4 Participants | 18 Participants | 2 Participants | 71 Participants |
| Age, Continuous | 63 Years STANDARD_DEVIATION 8.2 | 62 Years STANDARD_DEVIATION 7.3 | 66 Years STANDARD_DEVIATION 9.2 | 69 Years STANDARD_DEVIATION 9.1 | 71 Years STANDARD_DEVIATION 6.1 | 62 Years STANDARD_DEVIATION 8.4 | 63 Years STANDARD_DEVIATION 8.9 | 64 Years STANDARD_DEVIATION 8.1 | 69 Years STANDARD_DEVIATION 10.4 | 64 Years STANDARD_DEVIATION 8.2 |
| BMI at Screening | 25.04 kg/m^2 STANDARD_DEVIATION 4.82 | 25.43 kg/m^2 STANDARD_DEVIATION 5.113 | 30.72 kg/m^2 STANDARD_DEVIATION 7.595 | 24.63 kg/m^2 STANDARD_DEVIATION 2.43 | 29.05 kg/m^2 STANDARD_DEVIATION 6.218 | 26.06 kg/m^2 STANDARD_DEVIATION 7.164 | 28.11 kg/m^2 STANDARD_DEVIATION 6.232 | 26.13 kg/m^2 STANDARD_DEVIATION 4.239 | 24.15 kg/m^2 STANDARD_DEVIATION 3.502 | 25.79 kg/m^2 STANDARD_DEVIATION 4.984 |
| Body Surface Area at Screening | 1.81 m^2 STANDARD_DEVIATION 0.234 | 1.88 m^2 STANDARD_DEVIATION 0.234 | 2.11 m^2 STANDARD_DEVIATION 0.2 | 1.83 m^2 STANDARD_DEVIATION 0.398 | 2.05 m^2 STANDARD_DEVIATION 0.282 | 1.79 m^2 STANDARD_DEVIATION 0.398 | 2.01 m^2 STANDARD_DEVIATION 0.185 | 1.80 m^2 STANDARD_DEVIATION 0.234 | 1.76 m^2 STANDARD_DEVIATION 0.274 | 1.85 m^2 STANDARD_DEVIATION 0.255 |
| Body Weight at Screening | 71.9 kg STANDARD_DEVIATION 17.08 | 75.7 kg STANDARD_DEVIATION 17.28 | 95.2 kg STANDARD_DEVIATION 22.2 | 72.6 kg STANDARD_DEVIATION 23.59 | 90.1 kg STANDARD_DEVIATION 23.05 | 73.5 kg STANDARD_DEVIATION 29.88 | 86.3 kg STANDARD_DEVIATION 19.25 | 72.7 kg STANDARD_DEVIATION 16.37 | 67.8 kg STANDARD_DEVIATION 15 | 74.7 kg STANDARD_DEVIATION 18.55 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0-1 | 27 Participants | 29 Participants | 2 Participants | 3 Participants | 4 Participants | 6 Participants | 7 Participants | 27 Participants | 7 Participants | 112 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 31 Participants | 2 Participants | 3 Participants | 4 Participants | 8 Participants | 7 Participants | 28 Participants | 8 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Height at Screening | 169.0 cm STANDARD_DEVIATION 9.49 | 172.2 cm STANDARD_DEVIATION 10.01 | 176.2 cm STANDARD_DEVIATION 1.27 | 169.7 cm STANDARD_DEVIATION 18.53 | 175.3 cm STANDARD_DEVIATION 5.42 | 165.2 cm STANDARD_DEVIATION 12.93 | 175.3 cm STANDARD_DEVIATION 3.49 | 166.2 cm STANDARD_DEVIATION 9.85 | 167.4 cm STANDARD_DEVIATION 16.74 | 169.5 cm STANDARD_DEVIATION 10.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 29 Participants | 30 Participants | 2 Participants | 3 Participants | 4 Participants | 7 Participants | 6 Participants | 26 Participants | 7 Participants | 114 Participants |
| Region of Enrollment Belgium | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Croatia | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment North Macedonia | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Serbia | 3 participants | 12 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 11 participants | 0 participants | 26 participants |
| Region of Enrollment United States | 27 participants | 14 participants | 2 participants | 3 participants | 4 participants | 8 participants | 7 participants | 18 participants | 8 participants | 91 participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 0 Participants | 2 Participants | 0 Participants | 5 Participants | 0 Participants | 17 Participants | 4 Participants | 52 Participants |
| Sex: Female, Male Male | 16 Participants | 22 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 7 Participants | 12 Participants | 4 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 24 / 29 | 28 / 30 | 29 / 32 | 0 / 2 | 3 / 3 | 4 / 4 | 8 / 8 | 6 / 7 | 5 / 8 |
| other Total, other adverse events | 27 / 28 | 29 / 30 | 32 / 32 | 2 / 2 | 3 / 3 | 4 / 4 | 8 / 8 | 7 / 7 | 8 / 8 |
| serious Total, serious adverse events | 7 / 28 | 15 / 30 | 12 / 32 | 2 / 2 | 1 / 3 | 2 / 4 | 0 / 8 | 1 / 7 | 1 / 8 |
Outcome results
Primary
Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1
The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: * Absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting for ≥ 7 days * ≥ Grade 3 neutropenic infection/febrile neutropenia * Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding * Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10\^9/L and platelet count ≥ 100 × 10\^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT * ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for \> 72 hours)
Time frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days)
Population: The safety analysis set: All enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 | 2 Participants |
Primary
Duration of Severe (Grade 4) Neutropenia in Cycle 1
Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of \<0.5 × 10\^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10\^9/L that met the following criteria: (1) occurred after the ANC value of \<0.5 × 10\^9/L and (2) no other ANC values \<0.5 × 10\^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Time frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 8 days | Standard Deviation 6 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 1 days | Standard Deviation 3.1 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 2 days | Standard Deviation 3.9 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 14 days | Standard Deviation 1.4 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 8 days | Standard Deviation 6.8 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 0 days | Standard Deviation 0 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 0 days | Standard Deviation 0 |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 2 days | Standard Deviation 3.6 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Duration of Severe (Grade 4) Neutropenia in Cycle 1 | 3 days | Standard Deviation 5.5 |
Comparison: Analysis was for Part 2 data: Treatment difference was evaluated using a nonparametric analysis of covariance (ANCOVA). The nonparametric ANCOVA included study baseline ANC value as covariate, stratification factors of ECOG performance status (0 to 1 versus 2) and sensitivity to first line treatment (sensitive or resistant) and treatment as fixed effects.p-value: <0.0001non-parametric ANCOVA
Primary
Occurrence of Severe (Grade 4) Neutropenia
Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value \<0.5 × 10\^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Severe (Grade 4) Neutropenia | 22 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Severe (Grade 4) Neutropenia | 5 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Severe (Grade 4) Neutropenia | 13 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Severe (Grade 4) Neutropenia | 3 Participants |
Comparison: The occurrence of SN was a binary variable. Treatment group difference was analyzed using modified Poisson regression to account for the variable duration of the Treatment Period for each patient. The model included baseline ANC as a covariate, stratification factors of ECOG performance status (0 or 1 vs 2), sensitivity to 1st line treatment (sensitive or resistant), and treatment as fixed effects. The logarithm transformation of # of cycles was included as an offset variable in the modeling.p-value: 0.016Modified Poisson
Secondary
Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan
The weekly event rate of Major Adverse Hematologic Events (MAHE) events
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.258 events per participant/week |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.091 events per participant/week |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.102 events per participant/week |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.403 events per participant/week |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.156 events per participant/week |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.102 events per participant/week |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.037 events per participant/week |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.085 events per participant/week |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan | 0.073 events per participant/week |
Secondary
Chemotherapy Cycles and Modifications Overall
Average exposure and cycle modifications in chemotherapy (topotecan)
Time frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Population: Safety analysis set: All enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 4 cycles | Standard Deviation 3.4 |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 1.2 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 5 cycles | Standard Deviation 5.4 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 2 cycles | Standard Deviation 2.5 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 5 cycles | Standard Deviation 4.4 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 1.4 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 6 cycles | Standard Deviation 0 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 3 cycles | Standard Deviation 1.4 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 7 cycles | Standard Deviation 5 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 1.2 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 0.5 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 4 cycles | Standard Deviation 1.7 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 0.8 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 6 cycles | Standard Deviation 2.9 |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 4 cycles | Standard Deviation 3.4 |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 0 cycles | Standard Deviation 0.5 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles completed | 4 cycles | Standard Deviation 2.2 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Chemotherapy Cycles and Modifications Overall | Number of cycles delayed | 1 cycles | Standard Deviation 1 |
Secondary
Chemotherapy Exposure
Average duration of exposure to chemotherapy (topotecan) in days.
Time frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).
Population: Safety analysis set: All enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Chemotherapy Exposure | 94 days | Standard Deviation 75.9 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Chemotherapy Exposure | 110 days | Standard Deviation 132.1 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Chemotherapy Exposure | 109 days | Standard Deviation 97 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Chemotherapy Exposure | 147 days | Standard Deviation 9.9 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Chemotherapy Exposure | 147 days | Standard Deviation 116.9 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Chemotherapy Exposure | 102 days | Standard Deviation 38.9 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Chemotherapy Exposure | 124 days | Standard Deviation 65.8 |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Chemotherapy Exposure | 78 days | Standard Deviation 74.9 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Chemotherapy Exposure | 83 days | Standard Deviation 51.8 |
Secondary
Dose Reductions in Chemotherapy (Topotecan)
Overall event rate of dose reductions in chemotherapy (topotecan)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Dose Reductions in Chemotherapy (Topotecan) | 0.116 events per participant per cycle |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Dose Reductions in Chemotherapy (Topotecan) | 0.053 events per participant per cycle |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Dose Reductions in Chemotherapy (Topotecan) | 0.051 events per participant per cycle |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.500 events per participant per cycle |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.250 events per participant per cycle |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.118 events per participant per cycle |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.089 events per participant per cycle |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.040 events per participant per cycle |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Dose Reductions in Chemotherapy (Topotecan) | 0.036 events per participant per cycle |
Secondary
Duration of Response (DOR)
The median months and 95% CIs of duration of response.
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Population: Response-Evaluable analysis set: All patients who are in the mITT, have measurable disease (target lesions) at the baseline tumor assessment, and either (i) have at least 1 post-baseline tumor assessment, (ii) have clinical progression as noted by the investigator before their first post-baseline tumor scan, or (iii) have died due to disease progression before their first post-baseline tumor scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Duration of Response (DOR) | 4.9 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Duration of Response (DOR) | 7.8 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Duration of Response (DOR) | 6.8 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Duration of Response (DOR) | NA months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Duration of Response (DOR) | 5.4 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Duration of Response (DOR) | 6.7 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Duration of Response (DOR) | NA months |
Secondary
Need for Treatment With Hematopoietic Growth Factors
Percentage of patients requiring G-CSF administration.
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Need for Treatment With Hematopoietic Growth Factors | 19 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Need for Treatment With Hematopoietic Growth Factors | 8 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Need for Treatment With Hematopoietic Growth Factors | 16 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 4 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Need for Treatment With Hematopoietic Growth Factors | 3 Participants |
Secondary
Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations
The count of patients who received any ESA administration.
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 6 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 5 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 1 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations | 1 Participants |
Secondary
Occurrence of Febrile Neutropenia Adverse Events
Percentage of patients who experience febrile neutropenia adverse events
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Febrile Neutropenia Adverse Events | 5 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Febrile Neutropenia Adverse Events | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Febrile Neutropenia Adverse Events | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Febrile Neutropenia Adverse Events | 0 Participants |
Secondary
Occurrence of Grade 3 and 4 Hematologic Toxicities
The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Grade 3 and 4 Hematologic Toxicities | 27 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Grade 3 and 4 Hematologic Toxicities | 25 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Grade 3 and 4 Hematologic Toxicities | 29 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 3 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 4 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 7 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 7 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Grade 3 and 4 Hematologic Toxicities | 7 Participants |
Secondary
Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia)
The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 19 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 11 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 9 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 15 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 21 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 13 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 3 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 4 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 3/4 Thrombocytopenia | 4 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) | Overall Grade 4 Thrombocytopenia | 1 Participants |
Secondary
Occurrence of Infection Serious Adverse Events (SAEs)
Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Infection Serious Adverse Events (SAEs) | 3 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Infection Serious Adverse Events (SAEs) | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Infection Serious Adverse Events (SAEs) | 1 Participants |
Secondary
Occurrence of Intravenous (IV) Antibiotic Use
Percentage of patients requiring systemic/IV antibiotics
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Intravenous (IV) Antibiotic Use | 8 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Intravenous (IV) Antibiotic Use | 8 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Intravenous (IV) Antibiotic Use | 7 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 1 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Intravenous (IV) Antibiotic Use | 1 Participants |
Secondary
Occurrence of Platelet Transfusions
Percentage of patients requiring a platelet transfusion
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Platelet Transfusions | 9 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Platelet Transfusions | 4 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Platelet Transfusions | 8 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Platelet Transfusions | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Platelet Transfusions | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Platelet Transfusions | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Platelet Transfusions | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Platelet Transfusions | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Platelet Transfusions | 0 Participants |
Secondary
Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)
Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) | 1 Participants |
Secondary
Occurrence of RBC Transfusions
Percentage of patients requiring a RBC transfusion on/after week 5
Time frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Occurrence of RBC Transfusions | 12 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Occurrence of RBC Transfusions | 5 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Occurrence of RBC Transfusions | 10 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Occurrence of RBC Transfusions | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Occurrence of RBC Transfusions | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Occurrence of RBC Transfusions | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Occurrence of RBC Transfusions | 1 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Occurrence of RBC Transfusions | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Occurrence of RBC Transfusions | 2 Participants |
Secondary
Overall Survival (OS)
Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Overall Survival (OS) | 6.5 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Overall Survival (OS) | 5.8 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Overall Survival (OS) | 6.2 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Overall Survival (OS) | NA months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Overall Survival (OS) | 10.6 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Overall Survival (OS) | 8.3 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Overall Survival (OS) | 9.4 months |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Overall Survival (OS) | 4.4 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Overall Survival (OS) | 10.0 months |
Secondary
Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28)
Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)
Time frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Population: All patients who had evaluable PK profiles for both treatments and analytes.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 21.1 ng/ml | Geometric Coefficient of Variation 34.6 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 36.8 ng/ml | Geometric Coefficient of Variation 41.8 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 52.4 ng/ml | Geometric Coefficient of Variation 66.5 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | NA ng/ml | — |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 43.0 ng/ml | Geometric Coefficient of Variation 39 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 17.5 ng/ml | Geometric Coefficient of Variation 36.5 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) | 41.4 ng/ml | Geometric Coefficient of Variation 46.9 |
Secondary
Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan
Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan
Time frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.
Population: All patients who had evaluable PK profiles for both treatments and analytes.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | 1060 ng/ml | Geometric Coefficient of Variation 59 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | 1220 ng/ml | Geometric Coefficient of Variation 120 |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | 2220 ng/ml | Geometric Coefficient of Variation 75.2 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | 913 ng/ml | Geometric Coefficient of Variation 59.6 |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan | 1100 ng/ml | Geometric Coefficient of Variation 54.8 |
Secondary
Progression Free Survival (PFS)
Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause. Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days).
Population: The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Progression Free Survival (PFS) | 4.2 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Progression Free Survival (PFS) | 3.0 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Progression Free Survival (PFS) | 4.2 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Progression Free Survival (PFS) | 5.5 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Progression Free Survival (PFS) | 4.3 months |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Progression Free Survival (PFS) | 3.6 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Progression Free Survival (PFS) | 4.5 months |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Progression Free Survival (PFS) | 1.8 months |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Progression Free Survival (PFS) | 2.1 months |
Secondary
Tumor Response Based on RECIST, Version 1.1
The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.
Time frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).
Population: Response-Evaluable analysis set: All patients who are in the mITT, have measurable disease (target lesions) at the baseline tumor assessment, and either (i) have at least 1 post-baseline tumor assessment, (ii) have clinical progression as noted by the investigator before their first post-baseline tumor scan, or (iii) have died due to disease progression before their first post-baseline tumor scan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 1 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 2 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 2 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 6 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 10 Participants |
| Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 5 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 3 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 15 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 9 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 13 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 6 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 6 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 5 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 2 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 1 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 3 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 0 Participants |
| Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 6 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 1 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 3 Participants |
| Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Stable Disease (SD) | 3 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | No post-baseline tumor assessment (Missing) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Progressive Disease (PD) | 2 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Partial Response (PR) | 1 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Complete Response (CR) | 0 Participants |
| Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 | Tumor Response Based on RECIST, Version 1.1 | Not Evaluable (NE) | 0 Participants |