A phase 2 trial has been launched exploring a regimen including trilaciclib (Cosela), avelumab (Bavencio), and chemotherapy in the frontline setting for patients with locally advanced or metastatic urothelial carcinoma, according to G1 Therapeutics, the manufacturer of trilaciclib.1
In the study, known as PRESERVE 3, patients in the exploratory arm will receive the CDK4/6 inhibitor trilaciclib prior to frontline gemcitabine/platinum chemotherapy, followed by trilaciclib plus avelumab maintenance.
“Bladder cancer is unfortunately common and the five-year survival rate for metastatic urothelial carcinoma has not changed in the last 25 years, highlighting the need for new and well tolerated therapies specifically tailored for immune sensitive tumors like this,” Raj Malik, MD, chief medical officer at G1 Therapeutics, stated in a press release.
“While chemotherapy followed by avelumab maintenance therapy has proven to be a meaningful step forward for the 1L treatment of patients with mUC, patients may not receive the maximal benefit for a variety of reasons. These phase 2 data will be instructional and important to evaluate the benefit of adding Cosela to this regimen, and if positive, would be quickly followed by a phase 3 registrational trial,” added Malik.
Trilaciclib is a myeloprotection therapy that has been shown to help lower the occurrence of chemotherapy-induced myelosuppression.
The open-label PRESERVE 3 study has a target enrollment of 90 patients. Patients will be randomized in a 1:1 ratio. In the treatment arm, patients will receive upfront trilaciclib with subsequent gemcitabine/platinum chemotherapy followed by trilaciclib along with maintenance avelumab. The control arm will receive gemcitabine/platinum chemotherapy followed by maintenance avelumab. The chemotherapy regimen in both arms will be administered intravenously with or without trilaciclib in 21-day cycles. Avelumab maintenance in both arms will be administered intravenously with or without trilaciclib in standard 14-day cycles.
Stratification factors for randomization will be visceral metastasis and type of platinum-based chemotherapy to be delivered (cisplatin or carboplatin). Patients can receive 4 to 6 cycles of platinum-based chemotherapy. Those patients who do not have progressive disease after upfront chemotherapy are eligible to receive maintenance avelumab (with or without trilaciclib), until disease progression, withdrawal of consent, unacceptable toxicity, investigator decision, or the completion of the trial.
The primary end point is progression-free survival (PFS). Secondary end points include objective response rate, disease control rate, duration of response, PFS in the maintenance period, overall survival, the myeloprotective effects of trilaciclib on chemotherapy-induced myelosuppression, safety, and tolerability.
G1 Therapeutics noted in their press release that an initial readout of data from the study is anticipated to occur in the second half of 2022.
Trilaciclib is approved by the FDA to alleviate chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.
Avelumab is approved by the FDA as maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma without disease progression following frontline platinum-based chemotherapy.
1. G1 Therapeutics Initiates PRESERVE 3, A Randomized Phase 2 Study Of Cosela™ (Trilaciclib) In Bladder Cancer. Published online June 14, 2021. Accessed June 14 2021. https://bit.ly/3iDiR3W.