CDK4/6 is a key regulator of cell growth and proliferation in normal and malignant cells. Selective inhibition of CDK4/6 blocks the progression of cells from the G1-phase into the S-phase of the cell cycle.

Many tumors require CDK4/6 to proliferate and grow. These CDK4/6-dependent tumors include the most common types of prostate and breast cancer. Inhibiting CDK4/6 as a therapeutic strategy in these types of tumors has been clinically validated by the drug Ibrance®, which was approved by the FDA in 2015 for patients with estrogen receptor-positive, HER2-negative (ER+, HER2-) breast cancer. G1 is advancing G1T38 as a potential best-in-class oral CDK4/6 inhibitor in multiple CDK4/6-dependent tumors.

Some tumors do not require CDK4/6 for growth. These CDK4/6-independent tumors include small-cell lung cancer (SCLC) and triple-negative breast cancer (TNBC).  G1 is pioneering a unique therapeutic approach for these patients, via transient inhibition of CDK4/6 in key normal cells such as hematopoietic stem cells in the bone marrow (responsible for the generation of blood cells and the immune system). Trilaciclib (G1T28) is a potential first-in-class short-acting intravenous CDK4/6 inhibitor in development to preserve hematopoietic stem cells (HSCs) and enhance immune system function during chemotherapy.

G1’s clinical-stage CDK4/6 inhibitors: potential backbone therapy for multiple combination regimens