Neoplasms

All Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Hypersensitivity

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Avelumab

Talazoparib

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

* Talazoparib will be administered at the daily dose of 1 mg given orally in a 28-day cycle, except for patients with mild renal impairment (Creatinine clearance 30-59 mL/min) who will receive 0.75 mg per day.
* Avelumab will be administered by intravenous (I.V.) route over 60 minutes at the dose of 800 mg on D1 and D15, in a 28-day cycle.

Patients will receive the combined treatment until the investigator considers that the patient no longer obtains benefit from it. The treatment will be continued until disease progression, unacceptable toxicity or discontinuation for any cause.

Talazoparib + Avelumab

Elouen BOUGHALEM, MD

Thiery VUILLEMIN, MD

Hakim MAHAMMEDI, MD

Sylvain LADOIRE, MD

Aude FLECHON, MD

Gwenaelle GRAVIS, MD

Delphine BORCHIELLINI, MD

Camille SERRATE, MD

Ahmed KHALIL, MD

Laurence CROUZET, MD

Damien POUESSEL, MD

The main objectif is to determine the efficacy of a maintenance treatment combining Talazoparib and Avelumab after platinum-based chemotherapy in patients with locally advanced/metastatic urothelial carcinoma.

The first line treatment of urothelial carcinoma is a platinum-based chemotherapy. This treatment is efficient with a response rate \> 50 % but the progression-free survival is short (7.7 months) and the chemotherapy is too toxic to be used in a prolonged time. Traditionally, maintenance chemotherapy refers to the utilization of regimens with less toxicity after the initial upfront treatment. This concept has already been efficient with PARP inhibitors in ovarian carcinoma and more recently with durvalumab in lung carcinoma.

The prevalence of somatic mutations in homologous recombination genes in UC as well as their association with platinum sensitivity suggests Talazoparib to be a target for a maintenance treatment of urothelial carcinoma. Moreover, there is a strong rational with both pre-clinical and clinical data to associate Avelumab and Talazoparib. This appears all the more relevant that Avelumab has already demonstrated its efficacy in urothelial carcinoma (after platinum-based chemotherapy failure).

In this context, the sponsorpropose a phase 2 study to assess the antitumor activity of the combination of Avelumab plus Talazoparib in metastatic urothelial carcinoma in maintenance therapy after platinum-based chemotherapy.

Considering the doubts about the best molecular predictive factors of Talazoparib and Avelumab, the sponsor willingly propose a non-selective study, without molecular screening. Tumors will be selected according to the platinum sensitivity which has the advantage to exclude poor prognosis tumors and will allow increasing the HRD tumor population.

TALazoparib and Avelumab as Maintenance Therapy in Platinum-Sensitive Metastatic or Locally Advanced URothelial Carcinoma

TALazoparib and Avelumab as Maintenance Therapy in Platinum-Sensitive Metastatic or Locally Advanced URothelial Carcinoma: A Single-arm Phase 2 Trial

Pfizer

Centre Francois Baclesse

Spots Global Cancer Trial Database for talazoparib + avelumab