G1 Therapeutics

Trilaciclib – G1T28

Trilaciclib, a small molecule CDK4/6 inhibitor, is a first-in-class, FDA-designated Breakthrough therapy designed to improve outcomes for cancer patients being treated with chemotherapy.[8] The drug's first targeted indication is small cell lung cancer (SCLC).[9] Patients receiving chemotherapy as part of SCLC treatment frequently experience chemotherapy-induced myelosuppression.[10] In three randomized, placebo-controlled SCLC trials, trilaciclib, when administered to patients before chemotherapy, significantly reduced the occurrence of chemotherapy-induced myelosuppression and the need for supportive care.[11] In June 2020, G1 filed a New Drug Application (NDA) with the Food and Drug Administration (FDA).[12] The application was granted Priority Review with a Prescription Drug User Fee Act (PDUFA) date set for February 15, 2021.[13] In September 2020, G1 launched an expanded access program providing SCLC patients access to trilaciclib while the drug is under FDA review.[14] The FDA approved trilaciclib for use in SCLC on February 12, 2021.[15] In March 2021, trilaciclib was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) as an appropriate prophylactic option to decrease the incidence of chemotherapy-induced myelosuppression for patients undergoing chemotherapy for extensive-stage small-cell lung cancer.[16]

Trilaciclib is one of several novel agents under review for breast cancer treatment as part of the I-SPY series of clinical trials organized by Quantum Leap Healthcare Collaborative.[17]

In October 2020, G1 initiated a Phase 3 registrational study (NCT04607668 - PRESERVE 1)[18] evaluating the impact of trilaciclib on myelopreservation and antitumor efficacy in patients receiving chemotherapy for metastatic colorectal cancer.[19] In March 2021, the company initiated a Phase 3 registrational study (NCT04799249 - PRESERVE 2) evaluating trilaciclib in patients receiving first- or second-line gemcitabine and carboplatin chemotherapy for locally advanced, unresectable, or metastatic triple-negative breast cancer.[20] In April 2021, G1 initiated a Phase 2 study (NCT04863248 – PRESERVE 4) evaluating trilaciclib in patients with metastatic non-small cell lung cancer who are receiving the chemotherapy agent docetaxel.[21] In May 2021, G1 initiated a Phase 2 study (NCT04887831 – PRESERVE 3) evaluating trilaciclib in patients with metastatic bladder cancer who are receiving chemotherapy followed by avelumab.[22]

Rintodestrant – G1T48

Rintodestrant, an oral selective estrogen receptor degrader (SERD), is being developed as a treatment for ER-Positive, HER2-Negative advanced breast cancer, both as monotherapy and in combination with palbociclib, a CDK 4/6 inhibitor marketed by Pfizer as Ibrance.[23][24][25]

Lerociclib – G1T38

Lerociclib is a potent, selective oral CDK4/6 inhibitor. Preclinical and early clinical data have demonstrated that lerociclib is differentiated from other CDK4/6 inhibitors based on its favorable safety profile and ability to be dosed continuously with less dose-limiting neutropenia.[26]