Abstract 525P
Background
The oncogenic transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) promotes tumor survival and proliferation, while inhibiting differentiation. ST101 is a small peptide antagonist of C/EBPβ, with anti-tumor activity in glioblastoma (GBM), breast, prostate cancer (PC), melanoma and other models.
Methods
We conducted the phase 1 portion of a phase 1-2 study in pts with refractory solid tumors. The primary objective was to evaluate safety/tolerability of ST101. Secondary and exploratory objectives included PK, preliminary efficacy and PD from serial biopsies. The study used a 3+3 design, dosing ST101 IV at 0.5, 1, 2, 4, and 6 mg/kg weekly (QW). Phase 2 will include 4 cohorts of pts with specific cancers: breast, melanoma, GBM and castrate-resistant PC.
Results
As of May 2021, 15 pts were enrolled and the last cohort underway. Pts received a median of 6 weeks’ treatment (range 2 – 39). There were no DLTs, dose modifications or SAEs related to ST101. The only AEs of note were G1-2 histaminergic infusion-related reactions (IRRs), largely pruritis and urticaria, managed with antihistamines and interruption/slowing of infusion. IRRs affected 100% pts on 1st dose at ≥4mg/kg. Intensity and frequency of IRRs decreased with repeat dosing. No other AEs were consistently reported. PK was dose-proportionate, with continued exposure pre-dose QW, no evidence of accumulation and no anti-drug antibodies. Tumor immunohistochemistry showed dose-proportionate staining for ST101 and an inverse relationship with Ki67, suggesting decreasing tumor proliferation with increasing dose. There was 1 partial response in a pt with multi-metastatic cutaneous melanoma refractory to all standard therapy (confirmation pending) and 3 pts with varied histologies had stable disease lasting 18-39 weeks (1 ongoing).
Conclusions
ST101 demonstrated safety at all doses explored and evidence of efficacy across dose levels, particularly higher doses. PK and PD support a dose relationship for efficacy and selection of a QW dose to open phase 2 expansion cohorts by September 2021.
Clinical trial identification
ST101-101 (NCT04478279).
Editorial acknowledgement
Legal entity responsible for the study
Sapience Therapeutics.
Funding
Sapience Therapeutics.
Disclosure
M.A. Mckean: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Medpage Today; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Infinity; Financial Interests, Institutional, Research Grant: Jacobio; Financial Interests, Institutional, Research Grant: Moderna; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Tizona; Financial Interests, Institutional, Research Grant: Topalliance Biosciences; Financial Interests, Institutional, Research Grant: Prelude; Financial Interests, Institutional, Research Grant: Ascentage; Financial Interests, Institutional, Research Grant: Ideaya; Financial Interests, Institutional, Research Grant: Oncorus; Financial Interests, Institutional, Research Grant: Ikena; Financial Interests, Institutional, Research Grant: Tmunity; Financial Interests, Personal, Principal Investigator: Sapience Therapeutics. N.J. Lakhani: Financial Interests, Institutional, Sponsor/Funding: Beigene; Financial Interests, Personal, Advisory Role: Innovent; Financial Interests, Institutional, Sponsor/Funding: Innovent; Financial Interests, Institutional, Sponsor/Funding: ALX; Financial Interests, Institutional, Sponsor/Funding: Ascentage; Financial Interests, Institutional, Sponsor/Funding: Asana; Financial Interests, Institutional, Sponsor/Funding: Cpnstellation; Financial Interests, Institutional, Sponsor/Funding: alexion; Financial Interests, Institutional, Sponsor/Funding: cerulean; Financial Interests, Institutional, Sponsor/Funding: Forty Seven; Financial Interests, Institutional, Sponsor/Funding: Alpine; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Regeneron; Financial Interests, Institutional, Sponsor/Funding: TaiRx; Financial Interests, Institutional, Sponsor/Funding: Apexian; Financial Interests, Institutional, Sponsor/Funding: Formation biologics; Financial Interests, Institutional, Sponsor/Funding: Symphogen; Financial Interests, Institutional, Sponsor/Funding: CytomX; Financial Interests, Institutional, Sponsor/Funding: InhibRx; Financial Interests, Institutional, Sponsor/Funding: Incyte; Financial Interests, Institutional, Sponsor/Funding: Jounce; Financial Interests, Institutional, Sponsor/Funding: Lizvon; Financial Interests, Institutional, Sponsor/Funding: Northern Biologics; Financial Interests, Institutional, Sponsor/Funding: Ikena; Financial Interests, Institutional, Sponsor/Funding: Mersana; Financial Interests, Institutional, Sponsor/Funding: Odonate; Financial Interests, Institutional, Sponsor/Funding: Loxo; Financial Interests, Institutional, Sponsor/Funding: Alpine; Financial Interests, Institutional, Sponsor/Funding: Macrogenics; Financial Interests, Personal, Principal Investigator: Sapience Therapeutics. H. Arkenau: Financial Interests, Personal, Principal Investigator: Sapience Therapeutics. S. Symeonides: Financial Interests, Institutional, Training: Ipsen; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Advisory Role: Ellipses; Financial Interests, Institutional, Advisory Role: Vaccitech; Financial Interests, Institutional, Advisory Role: MedAnnex; Financial Interests, Institutional, Advisory Role: EUSA; Financial Interests, Institutional, Advisory Role: EISAI; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: EMD Serono; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Verastem; Financial Interests, Personal, Principal Investigator: BioLineRx; Financial Interests, Personal, Principal Investigator: BioNTech; Financial Interests, Personal, Principal Investigator: Boston; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Nouscom; Financial Interests, Personal, Principal Investigator: Sierra Oncology; Financial Interests, Personal, Principal Investigator: Verastem; Financial Interests, Personal, Principal Investigator: Sapience Therapeutics. T.R..J. Evans: Financial Interests, Institutional, Principal Investigator: Sapience Therapeutics. E.A. Lim: Financial Interests, Personal, Principal Investigator: Sapience Therapeutics; Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Other, Travel, accomodations, expenses: BMS. S.R. Chandana: Financial Interests, Personal, Advisory Role: Heron; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: J&J; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Role: Array; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Alexion; Financial Interests, Institutional, Research Grant: Alexo; Financial Interests, Institutional, Research Grant: Arqule; Financial Interests, Institutional, Research Grant: Asana; Financial Interests, Institutional, Research Grant: Ascentage; Financial Interests, Institutional, Research Grant: Beigene; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Cerulean; Financial Interests, Institutional, Research Grant: Constellation; Financial Interests, Institutional, Research Grant: DSI; Financial Interests, Institutional, Research Grant: Dicerna; Financial Interests, Institutional, Research Grant: Formation Biologics; Financial Interests, Institutional, Research Grant: Forty Seven; Financial Interests, Institutional, Research Grant: Lizvon; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Symphony evolution; Financial Interests, Institutional, Research Grant: TaiRx. J. Rotolo: Financial Interests, Personal, Full or part-time Employment: Sapience Therapeutics. G. Capiaux: Financial Interests, Personal, Advisory Role: Sapience Therapeutics. R. Michel: Financial Interests, Personal, Advisory Role: Sapience Therapeutics. S. Kaesshaefer: Financial Interests, Personal, Advisory Role: Sapience Therapeutics. A. Bexon: Financial Interests, Personal, Officer: Sapience Therapeutics; Financial Interests, Personal, Officer: Vyriad; Financial Interests, Personal, Officer: Bexon Clinical Consulting. G.S. Falchook: Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Advisory Role: Fujifilm; Financial Interests, Institutional, Advisory Role: Silicon; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Other, Travel: BMS; Financial Interests, Personal, Other, Travel: EMD Serono; Financial Interests, Personal, Other, Travel: Fujifilm; Financial Interests, Personal, Other, Travel: Millenium; Financial Interests, Personal, Other, Travel: SCRI; Financial Interests, Personal, Invited Speaker: Total Health Conferencing; Financial Interests, Personal, Invited Speaker: Rocky Mountain Oncology Society; Financial Interests, Institutional, Principal Investigator: 70 other biotechs and pharma companies. All other authors have declared no conflicts of interest.