Abstract 1402P
Background
Elevated serum Growth Differentiation Factor 15 (GDF15) has been observed in pts with prostate cancer (PC) and correlated with poor survival. Effects of GDF15 on tumor progression, metastasis and immune escape may play a role. NGM120, a novel antibody that blocks the effects of GDF15 through its receptor, GFRAL, has resulted both in antitumor and anti-cachexia effects in experimental models. Here we report initial results of NGM120 monotherapy from a phase 1a study in pts with advanced PC.
Methods
Five pts with advanced PC who had exhausted standard therapies with elevated serum GDF15 were treated with NGM120 (30 or 100 mg, s.c., q3wks). Pts had received ≥3 lines of therapies. Median age: 65.6 yrs; median serum PSA: 76 ng/ml; and median serum GDF15:16500 pg/ml. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics, preliminary evidence of antitumor (RESCIT, PSA) and anti-cachexia effects.
Results
NGM120 was well tolerated with no dose-limiting toxicities. Most of the AEs observed were grade 1 to 2 and not attributed to NGM 120 treatment. Two pts had PSA reduction, -32% and > -99% (< 0.1 ng/ml), respectively. The latter patient, who noted to have high levels of MicroSatellite Instability (MSI-H), partial response (PR) was observed with RECIST assessment. These responses have been sustained for 46 wks as of the data cut off. Furthermore, serum GDF15 was reduced up to 90% from baseline and body weight increased by up to 9.7% in this patient. Analysis of the circulating immune cell composition showed an increase of CD8 Tcm (central memory) pools and CD8+T cells with proliferative capacity (Ki67+) while a decrease of immuno-suppressive T-regulatory cells (Treg) and naïve T-reg pool.
Conclusions
NGM120 given as monotherapy to pts with advanced PC led to 2/5 PSA responses and 1/5 PR. The magnitude and durability of the PSA and anti-tumor response supports the potential role of NGM120 in the treatment of pts with advanced PC. The negative effects of GDF15 on body weight and immune modulation could potentially be blocked by NGM120 through GFRAL, a GDF15 receptor. A phase 1b trial has been initiated to confirm these findings in pts with PC, including those with MSI-H tumors.
Clinical trial identification
NCT04068896.
Editorial acknowledgement
Legal entity responsible for the study
NGM Biopharmaceuticals.
Funding
NGM Biopharmaceuticals.
Disclosure
H. Lenz: Financial Interests, Personal, Advisory Board: Bayer, Merck, Merck KG, BMS, G1 Therapeutics, Jazz Therapeutics, Fulgent. D. Mahalingam: Financial Interests, Institutional, Funding: Amgen, Merck, Oncolytics; Financial Interests, Personal, Advisory Board: Qurient, Oncoone; Financial Interests, Personal, Other, Consultant/speaker: BMS, Eisai, Exelixis. J. Thomas: Financial Interests, Personal, Other, Consultant: VasGene Therapeutics Inc. J. Luo, J. Zha, A. DePaoli, C. Tran-Muchowski, C. Tseng, H. Lieu: Financial Interests, Personal, Full or part-time Employment: NGM Biopharmaceuticals. All other authors have declared no conflicts of interest.