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G1 Therapeutics Presents Additional Data from Randomized Phase 2 Trial of Trilaciclib in Combination with Etoposide/Carboplatin for Treatment of First-Line Small Cell Lung Cancer
- New data analyses highlight myelopreservation and immune system benefits of trilaciclib in combination with chemotherapy
- Data presented at the
European Society for Medical Oncology( ESMO) 2018 Congress
"The totality of these favorable data highlight the unique, multi-lineage myelopreservation potential of trilaciclib. Trilaciclib demonstrated improvement in multiple hematological endpoints, including neutrophils, red blood cells and lymphocytes, which may improve outcomes for patients receiving chemotherapy. Trilaciclib may also enhance immune system function, potentiating the efficacy of chemotherapy/checkpoint combinations,” said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "Chemotherapy remains a cornerstone of cancer treatment, and emerging data support the use of chemotherapy/checkpoint combinations in an increasing number of indications. Trilaciclib may play an important role in multiple chemotherapy treatment regimens. In addition to the data presented at
The company reported topline data from this trial in
Myelopreservation Findings: Neutrophils and Red Blood Cells
- Neutrophils: consistent with previously reported data, treatment with trilaciclib compared to placebo reduced rates of Grade 4 absolute neutrophil count (ANC) (5.3 percent versus 43.2 percent; p=0.0001), Grade 4 ANC in the first chemotherapy cycle (2.6 percent versus 35.1 percent; p=0.0003) and granulocyte-colony stimulating factor (G-CSF) administration (10.5 percent versus 64.9 percent; p <0.0001). New analyses of the trial data showed that treatment with trilaciclib compared to placebo reduced median duration of Grade 4 ANC for patients who experienced an event (3 days versus 8 days; p=0.0097).
- RBCs: new analyses of the trial data showed that treatment with trilaciclib compared to placebo reduced rates of
RBCtransfusions (10.5 percent versus 24.3 percent; p=0.1109), transfusions on or after five weeks on study (5.7 percent versus 21.6 percent; p=0.0615) and Grade 3/4 hemoglobin values (10.5 percent versus 18.9 percent).
Myelopreservation Findings: Lymphocyte/Immune System Function
Analyses of absolute numbers and percentages of immune subsets were conducted by flow cytometry using peripheral blood samples.
Patients who received trilaciclib demonstrated faster recovery of lymphocytes following chemotherapy compared to those who received placebo. Analyses of lymphocyte subpopulations showed that the addition of trilaciclib to chemotherapy preserved or increased B and T lymphocyte counts, increased the total number of CD8+ T cells, and increased CD8+/regulatory T cell and activated CD8+/regulatory T cell ratios compared to placebo. Collectively, these data support that trilaciclib has the potential to preserve multiple immune system components and enhance CD8+ cell function. In preclinical studies, the presence of activated CD8+ cells and higher activated CD8+/regulatory T cell ratio have been shown to improve the efficacy of checkpoint inhibitors.
In this trial, measures of anti-tumor efficacy trended in favor of trilaciclib without reaching statistical significance. Overall response rate (complete response + partial response) for the response-evaluable population as assessed by investigators was 66.7 percent for trilaciclib versus 56.8 percent for placebo and median duration of response was 5.7 months for trilaciclib versus 5.4 months for placebo. Median progression free survival was 6.1 months for trilaciclib versus 5.0 months for placebo (hazard ratio 0.68; p=0.1286) and median overall survival (OS) was 10.9 months for trilaciclib versus 10.6 months for placebo (hazard ratio 0.86; p=0.5948). OS data are still immature; the company plans to provide an update in 2019. A greater percentage of patients receiving trilaciclib went on to additional lines of treatment compared to those receiving placebo (44.7 percent versus 40.5 percent).
Consistent with previously reported results, trilaciclib was well tolerated. TEAEs more commonly reported in the trilaciclib arm compared to placebo included fatigue, nausea, upper abdominal pain, and headache; the majority of these events were reported as Grade 1/2 in severity. There were no trilaciclib- related ≥ Grade 3 TEAEs reported.
This double-blind, placebo-controlled Phase 2 trial enrolled patients with a confirmed diagnosis of extensive-stage SCLC. The trial randomized 77 treatment-naïve patients in a 1:1 ratio, and 75 received trilaciclib or placebo administered intravenously prior to chemotherapy. Consistent with standard of care, patients generally received up to six cycles of chemotherapy. Patients in both arms of the trial were able to receive standard supportive care as recommended by the trial investigator. Growth factors, including G-CSF and erythropoietin, and transfusion support were available to all patients. Baseline demographics and disease characteristics were generally well balanced between the two arms. The statistical analysis plan prospectively defined several clinically relevant endpoints.
Both posters are available on the Publications page of the company’s website. For more information about the
Trilaciclib is a first-in-class myelopreservation therapy designed to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy and has the potential to significantly improve treatment outcomes.
Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. In
G1 is based in Research Triangle Park, NC. For additional information, please visit www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this news release include, but are not limited to, the therapeutic potential of trilaciclib, lerociclib and G1T48, and are based on G1 Therapeutics’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause G1 Therapeutics’ actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in G1 Therapeutics’ filings with the
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Source: G1 Therapeutics