Trilaciclib

Unassigned

New Medicines

Small cell lung cancer (SCLC) - adjunct preceding first-line chemotherapy

Information

New molecular entity
G1 Therapeutics
G1 Therapeutics

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Pre-registration (Filed)
Aug 20 · G1 Therapeutics announced that the US FDA have accepted the New Drug Application (NDA) for trilaciclib for SCLC pts being treated with chemotherapy. The FDA granted Priority Review with a PDUFA action date of February 15, 2021. Priority review is based on positive data from 3 randomised trials showing robust myelopreservation benefits.[5]
Nov 19 · G1 therapeutics intends to submit a NDA to the US FDA in Q2 20, and also file to the EMA in 2020 [4].
Aug 19 · Granted breakthrough therapy status in US [4].
Mar 18 · G1 Therapeutics plan to share PII data with US and EU regulatory authorities in 2018 to discuss next steps for the development of trilaciclib.[2]

Category

1st-in-class short-acting CDK4/6 inhibitor; preserves hematopoietic stem cells and enhances immune system function during chemotherapy
Lung cancer is the third most common cancers in the UK: about 46,400 new cases were diagnosed in the UK in 20143. About 1 in 5 cases are classified as SCLC [1].
Small cell lung cancer (SCLC) - adjunct preceding first-line chemotherapy
Intravenous

Trial or other data

Sep 19 · In the PII G1T28-05 trial, trilaciclib demonstrated myelopreservation benefits, as shown by statistically significant and clinically meaningful improvement in reduction of myelosuppression endpoints, reduction of chemotherapy side effects and reduction of rescue interventions. Trilaciclib was well tolerated, with fewer Grade 3 adverse events (AEs) compared to placebo. PRO measures related to anaemia were improved in patients receiving trilaciclib versus patients receiving placebo. Trilaciclib did not adversely impact chemotherapy anti-tumour efficacy as measured by ORR, PFS and OS [4].
Sep 19 · Results released from a PIIa G1T28-05 trial (NCT03041311). The trial was designed to assess the ability of trilaciclib in preserving the bone marrow and the immune system, and enhancing anti-tumour efficacy, when administered with carboplatin, etoposide, and atezolizumab as a first line treatment. In Sep 18, G1 Therapeutics reported that based on the positive myelopreservation results of the trial, the company has revised the trial protocol to evaluate myelopreservation as the primary endpoint, and overall survival as a secondary outcome. The US FDA and the EMA supported the change in primary endpoint. It enrolled 107 patients in Bulgaria, Estonia, France, Latvia, Spain, Ukraine and the US [4].
Dec 18 · Positive topline data from PIb/IIa trial (NCT02514447) released by the company [3].
Mar 18 · Trilaciclib is being evaluated in 4 randomised PII clinical trials: a trial in newly diagnosed including one in treatment-naive SCLC pts (NCT02499770). In this double-blind, placebo-controlled trial, 77 pts with extensive stage SCLC were enrolled. The pts were randomised (1:1), and 75 received trilaciclib or placebo administered i.v prior to each dose of standard-of-care (SOC) etoposide and carboplatin (EP) chemotherapy. Pts in both arms were able to receive standard supportive care. Growth factors, including G-CSF and erythropoietin, and transfusion support were available to all pts. Key haematological results indicated ~93% reduction in pts with Grade 4 Neutropenia in Cycle 1. Patients with febrile neutropenia saw a 68% haematological reduction. The lowest haematological reduction was at 41.6% in pts with chemotherapy cycle delays. Trilaciclib reduced “clinically relevant consequences of chemotherapy-induced myelosuppression” vs. placebo. Trilaciclib was well tolerated, with no Grade 3/4 trilaciclib-related treatment-emergent adverse events reported. Trilaciclib showed favourable trends versus placebo for overall response rate (trilaciclib 66.7%, placebo 62.2% (p=0.6759), duration of response (trilaciclib 5.7 months, placebo 4.3 months (p=0.1449)), and progression-free survival (trilaciclib 6.2 months, placebo 5.0 months (hazard ratio 0.6, p=0.06)). [2]