Abstract B017: Phase 2 Study of NP-G2-044, a Novel Fascin Inhibitor, in Combination with Anti-PD-1 Therapy in Patients with Solid Tumors Resistant to Prior Anti-PD-1 Therapy
Authors: Kasi Anup , Birrer Michael , Brown Jason , Chandrasekaran Sanjay , Chung Vincent , Frank Richard , Gadgeel Shirish , George Thomas , Jalal Shadia , Mendivil Alberto , Poklepovic Andrew , Segar Jennifer , Spira Alexander , Tanyi Janos , Zhang Jillian , Huang Xin-Yun , Jimeno Jose , Tsai Frank v 
Published: February 2025

NP-G2-044 is a first-in-class novel fascin inhibitor that targets fascin proteins in both tumor cells and intratumoral dendritic cells (DCs). Fascin, the primary actin-bundling protein plays a critical role in cell migration and tumor metastasis. NP-G2-044 blocks tumor metastasis, reduces tumor growth, and activates intratumoral DCs by enhancing antigen uptake and increasing the population of activated DCs leading to the proliferation of CD8+ T cells. NP-G2-044 is an oral first-in-class anti-metastasis agent and simultaneously synergizes with ICIs to enhance anti-tumor immune response. Over 100 treatment-refractory patients with solid tumors have been treated with daily NP-G2-044. No DLTs have been observed. Over 70% of patients treated with NP-G2-044 in clinical trials did not develop new metastases. Here we report findings from our Phase 2 study evaluating NP-G2-044 in combination with SOC anti-PD-1 therapy in patients with advanced solid tumors. Among the 45 patients treated with NP-G2-044, 80% had progressed on prior anti-PD-(L)1 therapies. The primary endpoint was objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival (OS), safety, and tolerability. Treatment has been well tolerated with reversible elevations of liver enzymes (LFT) being the most common adverse events (~30%). In most of the cases LFT increase was a single time event and preceded the onset of response. Long lasting objective responses have been observed independently of PD-L1 status. Results indicate durable responses and tumor control in a significant proportion of patients across at least seven cancer types, including cases converted from ICI-non-responsive to ICI-responsive. Notable outcomes include a complete response (CR) in a cervical cancer patient, target lesion CR in an endometrial cancer patient, pathological CRs in a pancreatic cancer patient and a patient with gastroesophageal junction adenocarcinoma, and partial responses (PR) in cutaneous squamous cell carcinoma, non-small cell lung cancer, and cholangiocarcinoma. Seven patients are still on treatments with the longest duration at 14+ months. These findings indicate that NP-G2-044 provides a novel therapeutic opportunity when combined with ICIs. This simultaneous inhibition of metastasis and enhancement of cancer immunotherapy represents a promising and innovative approach in cancer treatment with broad applications for many solid tumors. An amendment to the study is underway to open additional cohorts. These new cohorts aim to further evaluate the combination of NP-G2-044 with anti-PD-1 therapy across patient populations and solid tumor subtypes, providing a broader understanding of its therapeutic potential. Future analysis will also explore biomarkers for response prediction and mechanisms of resistance, guiding personalized approaches in treatment-resistant cancer.

Citation Format: Anup Kasi, Michael Birrer, Jason Brown, Sanjay Chandrasekaran, Vincent Chung, Richard Frank, Shirish Gadgeel, Thomas George, Shadia Jalal, Alberto Mendivil, Andrew Poklepovic, Jennifer Segar, Alexander Spira, Janos Tanyi, Jillian Zhang, Xin-Yun Huang, Jose Jimeno, Frank v Tsai. Phase 2 Study of NP-G2-044, a Novel Fascin Inhibitor, in Combination with Anti-PD-1 Therapy in Patients with Solid Tumors Resistant to Prior Anti-PD-1 Therapy [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B017.