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
5444 - Analysis of the tumor microenvironment and tumor genotype through different stages of lung adenocarcinoma
Presenter: Peter Zink
Session: Poster Display session 1
Resources:
Abstract
3124 - Does Progress achieved in the Treatment of Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) reach the Elderly Population?
Presenter: Jorune Suipyte
Session: Poster Display session 1
Resources:
Abstract
5142 - Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
Presenter: Yoshihito Ohhara
Session: Poster Display session 1
Resources:
Abstract
1580 - A novel risk classification system based on nomogram scores to predict survival of patients presenting with brain metastases at the first diagnosis of NSCLC
Presenter: Pengfei Cui
Session: Poster Display session 1
Resources:
Abstract
4442 - Comparison of real-world response rate (rwRR) to RECIST-based response rate in patients with advanced non-small cell lung cancer (aNSCLC)
Presenter: Xinran Ma
Session: Poster Display session 1
Resources:
Abstract
5405 - Estimating the cost and survival impact of new aNSCLC therapies in Canada with the iTEN model
Presenter: Parneet Kaur Cheema
Session: Poster Display session 1
Resources:
Abstract
1893 - SMARCA4 Deficient Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Genomic Profiling (CGP) Study
Presenter: Stephen Graziano
Session: Poster Display session 1
Resources:
Abstract
5582 - Exploring Resistance to Nivolumab [NIV] applying an Immune Genomic Signature (IGS) in advanced pretreated NSCLC [PRINCiPe study]
Presenter: Sara Pilotto
Session: Poster Display session 1
Resources:
Abstract
1408 - DNA damage repair deficiency is associated with early resistance to crizotinib: whole-genome analysis in non-small cell lung cancer patients with ALK-fusion
Presenter: Dongyun He
Session: Poster Display session 1
Resources:
Abstract
5751 - Phase 3 ALTA-3 study of brigatinib (BRG) vs alectinib (ALC) in patients (pts) with advanced anaplastic lymphoma kinase (ALK)−positive non–small cell lung cancer (NSCLC) that progressed on crizotinib (CRZ)
Presenter: Sanjay Popat
Session: Poster Display session 1
Resources:
Abstract