Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study.

Background: Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumour activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. The phase 2 LITESPARK-003 study was designed to determine the antitumour activity and safety of belzutifan in combination with cabozantinib in patients with advanced clear-cell renal cell carcinoma that was previously untreated (cohort 1) or previously treated with immunotherapy (cohort 2). Here, we report results from cohort 1 of this clinical trial.

A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors.

Background: The Wnt pathway is involved in proliferation and tissue homeostasis. Aberrant activation promotes cancer cell proliferation and survival. Inhibition of the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) coreceptors that regulate Wnt signaling could prevent cancer cell proliferation.

Open-Label, Multicenter, Phase I Study to Assess Safety and Tolerability of Adavosertib Plus Durvalumab in Patients with Advanced Solid Tumors.

Background: Adavosertib (AZD1775) is a small-molecule Wee1 inhibitor. Durvalumab is a PD-L1 inhibitor.

Objective: The safety, tolerability, pharmacokinetics, and preliminary antitumor activity of adavosertib plus durvalumab were evaluated in patients with refractory solid tumors to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D).

Adavosertib in Combination with Olaparib in Patients with Refractory Solid Tumors: An Open-Label, Dose-Finding, and Dose-Expansion Phase Ib Trial.

Background: Adavosertib is a first-in-class, selective small-molecule inhibitor of Wee1. Olaparib is an inhibitor of poly(ADP-ribose) polymerase (PARP). Preclinical data suggest that adavosertib enhances the antitumor effect of PARP inhibitors.