On June 13, 2022, Simcere Pharma (2096.HK) announced that a global multi-center pivotal Phase 3 clinical trial (PRESERVE1 study) of Trilaciclib, an innovative drug in collaboration with G1 Therapeutics in patients with metastatic colorectal cancer (mCRC) has completed the enrollment of all patients.
This randomized, double-blind, placebo-controlled, global, multicenter, Phase 3 trial involves more than 120 study centers across the world, with 10 centers located in China. A substantial number of Chinese patients were enrolled, to evaluate the impact of trilaciclib on myelopreservation and anti-tumor efficacy when administered prior to FOLFOXIRI/bevacizumab in patients with pMMR/MSS mCRC who have not received systemic therapy for metastatic disease. As part of the global study, Simcere’s participation in fueling patient enrolment in China further accelerated the global clinical progress of trilaciclib.
“Trilaciclib may be an important addition to this regimen due to its unique ability to preferentially protect the bone marrow from chemotherapy-induced toxicities” said Raj Malik, M.D., G1’s Chief Medical Officer，“We are thrilled to have completed enrollment, and look forward to presenting data, including the primary endpoint of the trial, in early 2023. I’d like to thank the patients enrolled in the trial, the clinical investigators, our CRO partners, and the G1 team who worked tirelessly and under extraordinarily challenging conditions to advance the trial to this stage.”
Ms. Wenjie Song, Simcere’s senior Vice president said: "I am delighted to see that the PRESERVE1 study has reached an important milestone, which is the result of the joint efforts and patient-centric collaboration between Simcere and G1, as well as global clinical experts. Colorectal cancer is a malignancy with highest morbidity and mortality globally. Patients have huge clinical needs for safer and more effective treatment options. We look forward to accelerating the progress of clinical research, which will benefit patients around the world sooner.”
According to the 2022 National Cancer Report released by the China National Cancer Center, there are about 400,000 newly diagnosed colorectal cancer patients and nearly 200,000 deaths in China annually. Most patients are at medium or advanced stages at first diagnosis. Metastatic colorectal cancer (mCRC) accounts for nearly 40% of the total number of CRC patients.
Fluorouracil-based chemotherapies are recommended by clinical guidelines in both China and the US for mCRC patients as standard treatment. Myelosuppression caused by chemotherapy is a serious adverse reaction which may lead to a dramatic decline in the quality of life of patients, requiring dose reduction and delay , affecting the therapeutic effect. There are huge unmet clinical needs in protecting bone marrow stem cells before chemotherapy induces adverse reactions.
Trilaciclib, co-developed by Simcere Pharma and G1 therapeutics, is the world's first and the only chemotherapy companion agent with comprehensive myeloprotective effect. It is marketed by G1 in the US under the trade name COSELA®, and has entered the NCCN Guidelines for Small Cell Lung Cancer 2021 edition, and CSCO Diagnosis and Treatment Guidelines for Small Cell Lung Cancer 2022 edition.
As a short-acting and reversible CDK4/6 inhibitor administered before chemotherapy, trilaciclib puts healthy cells such as bone marrow hematopoietic stem cells into temporary arrest in the G1 phase of the cell cycle, reducing DNA damage during exposure to chemotherapy. Several published clinical studies have shown that trilaciclib has achieved good results in multiple clinical myeloprotection indicators e.g. the incidence of severe neutropenia, the proportion of grade 3/4 thrombocytopenia, and the proportion of blood component transfusions. Trilaciclib is also shown to have significantly reduced the damage of chemotherapy to the hematopoietic function of neutrophils, erythrocytes and platelets. Therefore, it is expected to be used as a chemotherapy companion drug that increases efficacy and reduces toxicity of chemotherapy.
After the collaboration between Simcere and G1, three pivotal registration studies of Trilaciclib for three potential indications in China were initiated，including extensive-stage small cell lung cancer（ES-SCLC）, metastatic colorectal cancer（m-CRC）, and metastatic triple-negative breast cancer（m-TNB）. The clinical phase III study (TRACE study) of trilaciclib in patients with ES-SCLC spent only 10 months from the first Chinese IND to NDA submission and has reached the primary research endpoint. Priority review designation has been obtained from the State Food and Drug Administration for the first indication. Trilaciclib is expected to be approved for marketing in China in 2022.