Abstract 4615
Background
BPM31510-IV is a ubidecarenone (CoQ10) containing IV nanodispersion evaluated for safety and tolerability alone or in combination with chemotherapy in a phase 1 solid tumor study. In addition to clinical monitoring, an extensive pre- and post-treatment PD sampling was evaluated to generate comprehensive multi-omic profiles enabling post-hoc analysis of drug exposure to molecular analytes and pathways identifying the mechanism(s) driving clinical endpoints.
Methods
Patients relapsed/refractory to standard therapy were enrolled either in the monotherapy arm with BPM31510 alone or in combination arms with gemcitabine, 5-FU or docetaxel. BPM31510-IV was administered as 96 h or 144 h continuous infusion. Endpoints included assessment of DLT, MTD, safety & tolerability, PK and assessment of tumor response evaluated at cycle 1 (28 days) and then after every 2 cycles. An 18 point PD sampling in Cycle 1 and 8 point sampling in Cycle 2 to collect plasma and buffy coat and optional tumor core biopsy (pre- and post-treatment) was obtained for comprehensive multi-omic profiling.
Results
A total of 104 patients were enrolled (33 monotherapy, 71 combination therapy) and included in the Safety Population; 99% patients receiving ≥ 1 treatment with BPM31510 experienced a TEAE. The most frequently (> 50% patients) experienced TEAEs were coagulation related including prolonged Prothrombin Time (PT), elevated INR and/or prolonged PTT and managed by administration of Vitamin K. Analysis of molecular proteomic datasets from the patients identified significant changes in levels of proteins directly or indirectly involved in the Complement and Coagulation Cascade (KEGG analysis: 37 proteins, q = 2.51-44). Specifically, changes in the levels of vitamin K dependent coagulation factors (Prothrombin, Protein S, Complement C6 and others) were identified, suggestive of effect of BPM31510 on coagulation cascade.
Conclusions
BPM31510-IV is well tolerated alone and in combination with chemotherapeutic agents. Proteomic profile based insights on Mechanism of Action (MOA) and adverse events will be used in Phase 2/3 clinical development.
Clinical trial identification
NCT01957735.
Editorial acknowledgement
Legal entity responsible for the study
BERG LLC.
Funding
BERG LLC.
Disclosure
E. Granger: Leadership role, Full / Part-time employment, Officer / Board of Directors: BERG, LLC. M. Kiebish: Leadership role, Full / Part-time employment: BERG, LLC. G. Miller: Full / Part-time employment: BERG, LLC. L. Zhang: Full / Part-time employment: BERG, LLC. V. Vemulapalli: Full / Part-time employment: BERG, LLC. L. Rodrigues: Leadership role, Full / Part-time employment: BERG, LLC. N. Narain: Leadership role, Full / Part-time employment, Officer / Board of Directors: BERG, LLC. R. Sarangarajan: Leadership role, Full / Part-time employment: BERG, LLC. All other authors have declared no conflicts of interest.
Resources from the same session
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract