GSK2636771

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Nov 2023 --> Nov 2024

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents.

P1/2, N=27, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

In PTEN-present tumors, BYL719 (BYL, a PI3Kα inhibitor) synergized with αPD1 to delay tumor growth and extend survival (median survival of MC38-bearing mice in control (Ctrl), BYL, αPD1, and combination (Comb) groups: 30, 36, 33, and >45 respectively; p<0.05: Ctrl/BYL/αPD1 vs Comb). However, a limited combinatorial effect between GSK2636771(a PI3Kβ inhibitor) and αPD1 was observed in PTEN-present tumor models...Collectively, our results demonstrate that PI3Kα inhibitor can potentiate T cell-mediated antitumor immune responses regardless of PTEN status, providing a strong rationale for the clinical development of the BYL-based IO combination. In collaboration with Novartis, MD Anderson Cancer Center will launch a Phase I/II trial of the FDA-approved BYL in combination with αPD1 in advanced melanoma and breast cancer patients.

P1/2, N=27, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Nov 2022 --> Nov 2023

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Nov 2022 --> Nov 2023

P2, N=400, Active, not recruiting, Yonsei University | Phase classification: P=N/A --> P2 | Trial completion date: Jun 2022 --> Dec 2022

GSK2636771 plus pembrolizumab had an acceptable safety and tolerability profile. The combination showed promising preliminary antitumor activity and durable responses in a heavily pretreated population of pts with mCRPC.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: May 2022 --> Nov 2022

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: May 2022 --> Nov 2022

P2, N=6452, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2022 --> Dec 2025 | Trial primary completion date: Jun 2022 --> Dec 2025

To explore the therapeutic potential of simultaneously targeting Cx43 and PIK3CB/p110β, αCT1 is combined with TGX-221 or GSK2636771, two PIK3CB/p110β-selective inhibitors. These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo. Our study has revealed novel mechanistic insights into Cx43/PI3K-mediated temozolomide resistance in glioblastoma and demonstrated that targeting Cx43 and PIK3CB/p110β together is an effective therapeutic approach for overcoming chemoresistance.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | N=24 --> 35 | Trial primary completion date: Nov 2020 --> May 2022

G771 (200 mg PO QD) + P was tolerable, but response was modest. Translational studies will be critical to understanding mechanisms of response and resistance to G771 + P and to develop additional strategies to overcome resistance to ICB due to PTEN loss.

Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Nov 2020 --> May 2022

P=N/A, N=400, Active, not recruiting, Yonsei University | Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Dec 2020 --> Dec 2021

P1/2, N=42, Completed, Yonsei University | Active, not recruiting --> Completed

P1/2, N=36, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2020 --> Dec 2022

P2, N=24, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2019 --> Nov 2020

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2019 --> Nov 2020

P1/2, N=42, Active, not recruiting, Yonsei University | Trial primary completion date: Jun 2020 --> Jan 2021

These results highlight a critical role of OX40 activation in potentiating the effector function of tumor-reactive CD8 T cells and suggest further evaluation of OX40 agonist-based combinations in patients with immune-resistant tumors.

P1/2, N=41, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2021 --> Dec 2022 | Trial primary completion date: Jul 2020 --> Dec 2020

The combination of G and P is being explored at the RP2D of 200 mg. Renal toxicity precluded higher doses. No objective responses have been observed although 2 pts have experienced prolonged clinical benefit including a MM pt with 27% decrease in tumor burden.

We demonstrate that a selective Group A PAK inhibitor (Frax-1036), a pan-PI3K (BKM120), and two PI3Kβ inhibitors (TGX221, GSK2636771) impede the growth of melanoma cells driven by mutant RAC1 but not by mutant BRAF, while other PI3K selective inhibitors, including PI3Kα, δ and γ, are less effective. Using these compounds as well as an SRF/MRTF inhibitor (CCG-203971), we observed similar results in vivo, using embryonic zebrafish development as a readout. These results suggest that targeting Group A PAKs, PI3Kβ, and/or SRF/MRTF represent a promising approach to suppress RAC1 signaling in malignant melanoma.

P1/2, N=42, Active, not recruiting, Yonsei University | Recruiting --> Active, not recruiting | N=66 --> 42 | Trial primary completion date: Dec 2019 --> Jun 2020

P=N/A, N=400, Recruiting, Yonsei University | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Dec 2019 --> Dec 2020

P1, N=35, Completed, GlaxoSmithKline | Active, not recruiting --> Completed