Advanced Squamous Non-Small Cell Lung Carcinoma Clinical Trial
Official title:
A Phase 1b/2, Multicenter, Single Arm Study of RBN-2397 in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung (SCCL)
RBN-2397 inhibits PARP7, an enzyme that is switched on by cancer stresses, such as the toxins in cigarette smoke. Cancer cells use PARP7 to hide from the immune system by stopping the cell from sending a signal (Type 1 interferon) that tells the immune system that something is wrong and to kill the cell. RBN-2397 has been shown in animal and human studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor is sending to evade the immune system. The purpose of this study is to determine if RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) has the ability to restore the response to treatment in patients with SCCL that have been previously treated with a PD-1/PD-1 ligand (PD-L1) inhibitor and have had a response followed by disease progression. The Phase 1b portion of the study will assess the safety of RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) and define the dose of RBN-2397 to be used in combination with pembrolizumab for the Phase 2. The Phase 2 portion of the study will assess the anti-tumor activity of RBN-2397 in combination with pembrolizumab.
This is an open label, multicenter Phase 1b/2 single arm study that will evaluate the safety and antitumor activity of RBN-2397 in combination with pembrolizumab in patients with confirmed diagnosis of advanced squamous cell carcinoma of the lung who have received prior therapy. The study consists of a Phase 1b Safety Run in and Phase 2. During the Phase 1b Safety Run-in, approximately 10 patients will be enrolled in a 3+3 fashion and treated with continuous oral dosing with RBN-2397 twice daily (BID) in combination with the fixed approved dose of intravenous (IV) pembrolizumab every 3 weeks [Q3W]) to establish RP2D of RBN-2397 in combination with pembrolizumab. During Phase 2, approximately 40 patients will be treated with continuous oral dosing with the RP2D of RBN-2397 BID in combination with the fixed approved dose of IV pembrolizumab. In both the Phase 1b Safety Run in and Phase 2, a treatment cycle is defined as 21 days. On Day 1 of each treatment cycle, RBN-2397 will be administered orally and followed by IV infusion of pembrolizumab at the fixed approved dose according to the approved local product label. During the remaining days of the 21-day treatment cycle, only RBN-2397 BID will be administered. Treatment cycles will continue until disease progression, unacceptable treatment-related toxicity, or withdrawal of consent ;