Avelumab Plus Trilaciclib Elicits Responses in Phase 2 Urothelial Carcinoma Study


Patients with previously untreated, locally advanced or metastatic urothelial carcinoma responded to treatment with trilaciclib and avelumab.

Platinum-based chemotherapy plus maintenance avelumab (Bavencio) in combination with trilaciclib yielded responses in patients with untreated, locally advanced or metastatic urothelial carcinoma, according to initial data from the phase 2 PRESERVE3 trial (NCT04887831) published by G1 Therapeutics.

The data showed that the trilaciclib arm (n = 45) had a confirmed objective response rate (ORR) of 40.0% (n = 18) vs a rate of 46.7% (n = 21/45) in the control arm, as assessed per RECIST v1.1 criteria. Investigators noted that longer term follow-up is needed to determine the treatment’s other anti-tumor end points such as median duration of response (DOR) and progression-free survival (PFS).

Additionally, the safety profile observed in the trilaciclib arm was consistent with the profile observed in the control arm. The data monitoring committee (DMC) has recommended continuation of the study.

Investigators expect to present the study’s primary findings, including PFS data, at a medical meeting later in 2023.

“The immunomodulatory mechanism of action of trilaciclib lends itself to longer term anti-tumor efficacy endpoints like PFS, as opposed to shorter term response rate endpoints, as was noted in the Phase 2 trial in triple negative breast cancer,” Raj Malik, MD, chief medical officer at G1 Therapeutics, said in the press release. “We look forward to the results of the maintenance portion of this trial, particularly given the preclinical work that we have conducted showing the potential synergy of trilaciclib with checkpoint inhibitors—which we seek to validate clinically in this study with longer term duration of response and PFS data.”

Trilaciclib is a first-in-class, intravenous, transient CDK4/6 inhibitor designed to preserve bone marrow and immune system function during chemotherapy. Depending on the tumor type and chemotherapy backbone, the mechanism could provide myeloprotection and anti-tumor efficacy. This method—enhancing overall immune response via improvement of long-term immune surveillance—lends itself to long-term study through measures like PFS.

The phase 2 PRESERVE3 trial is a randomized, open-label study assessing a total population of 94 patients, randomly assigned 1:1 to receive either trilaciclib followed by gemcitabine/platinum chemotherapy followed by trilaciclib plus avelumab maintenance therapy or chemotherapy and avelumab maintenance alone.

The primary end point is PFS, and key secondary end points include ORR, DOR, PFS in the maintenance period, overall survival, and the probability of survival at month 16. Investigators also seek to survey the myeloprotective effects of trilaciclib on chemotherapy-induced myelosuppression.

To enroll on the study, patients were not allowed to have received any prior systemic therapy in the inoperable, locally advanced, or metastatic setting; these include chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents. An available archival tumor tissue or biopsy was also required, though this criterion could be waived by the Medical Monitor. Patients also needed to have an ECOG performance status of 2 or lower and adequate organ function.

The study excluded patients who had malignancies other than urothelial carcinoma in the 3 years prior to randomization, save for those with adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or cervix, or low-grade prostate cancer under surveillance without any plans for treatment intervention. Other exclusion criteria included the presence of central nervous system (CNS) metastases or leptomeningeal disease requiring immediate treatment, known hypersensitivity to the primary study agents besides trilaciclib, and receipt of any prior hematopoietic stem cell, bone marrow, or solid organ transplantation.


G1 Therapeutics provides initial update on phase 2 bladder cancer trial; progression free survival (PFS) data expected in mid-2023. News Release. G1 Therapeutics, Inc. January 4, 2023. Accessed January 5, 2023. https://bit.ly/3QfbWN7

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