Trilaciclib

Trilaciclib

Trilaciclib, a transient IV-administered CDK4/6 inhibitor, is a novel therapeutic approach which is given before chemotherapy that temporarily blocks progression through the cell cycle. This provides two potential benefits: (1) bone marrow protection - and therefore the immune system - from damage caused by cytotoxic therapy, and (2) improved long term immune surveillance by upregulating the formation of certain memory T cells.  Trilaciclib is being evaluated a number of tumor types and chemotherapy regimens to assess its potential myeloprotection, antitumor efficacy and safety in combination with cytotoxic therapiesand other anticancer agents.


Small cell lung cancer (SCLC)

See product page for additional information.


Breast cancer

According to the World Health Organization, an estimated 2.3 million cases of breast cancer are diagnosed annually worldwide. Triple-negative breast cancer, or TNBC, makes up approximately 15-20% of such diagnosed breast cancers. Because TNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer and is more likely than some other types of breast cancer to return after it has been treated.

G1 is conducting multiple clinical trials in patients living with TNBC.

  • PRESERVE 2 is  a pivotal registrational Phase 3, randomized, double-blind, placebo-controlled study of trilaciclib in patients receiving first-line gemcitabine and carboplatin chemotherapy for TNBC. The trial is evaluating the potential survival impact of trilaciclib in 170 patients with locally advanced unresectable or metastatic TNBC. More information on the trial, including enrollment criteria and clinical trial sites, is available here.

 

G1 has also conducted two  additional Phase 2 trial of trilaciclib:

  • The Company is assessing trilaciclib in combinataion with an antibody-drug conjugate (ADC) in 2L/3L TNBC. Initial results presented at the 2023 European Society for Medical Oncology (ESMO) Breast meeting showed that trilaciclib administered prior to the ADC was associated with clinically meaningful reductions of over 50% in the rates of multiple adverse events compared to the single agent safety profile of sacituzumab, including certain myelosuppressive events (neutropenia, anemia, etc.), and diarrhea. We believe that having a healthier bone marrow and immune system function with trilaciclib treatment may help patients live longer.
  • A second Phase 2 trial was completed to confirm the mechanism of action of trilaciclib in neoadjuvant TNBC.  Results presented at the 2023 American Society of Clinical Oncology (ASCO) meeting  added to the data supporting the ability of trilaciclib to enhance long term immune surveillance by increasing T cell function, and generation of certain memory T cells and gene expression profiles that may be associated with improved clinical outcome. This would be expected to produce a greater effect on overall survival compared to earlier efficacy measures such as ORR and PFS, consistent with other immunotherapies. The press release announcing these results can be found here


Bladder cancer

Bladder cancer is the most common malignancy involving the urinary system and is the sixth most common cancer in the United States. According to the American Cancer Society, there are over 81,000 new cases of bladder cancer diagnosed in the United States each year, and over 17,000 reported annual deaths. Globally, there are nearly 575,000 new bladder cancer diagnoses each year.  

  • The Company has completed PRESERVE 3, a Phase 2, randomized, open-label study of trilaciclib administered with first-line platinum-based chemotherapy and the immune checkpoint inhibitor avelumab maintenance therapy in patients with untreated, locally advanced or metastatic urothelial carcinoma (mUC).  This trial will conclude in the fourth quarter of 2023 following the next protocol defined analyses of survival. PRESERVE 3 is a signal finding study designed to assess the potential additive contribution of trilaciclib to anti-cancer therapy, including in combination with the immune checkpoint inhibitor avelumab alone without chemotherapy during the maintenance part of the study. To date, an overall survival trend in favor of the trilaciclib plus avelumab arm in the maintenance phase was observed, suggesting a potential additive benefit when used in combination with a checkpoint inhibitor, which will inform future studies in G1's core areas of focus. The Company intends to report the results at a future medical meeting.

 

Last update: November 10, 2023