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
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC
Presenter: Petros Christopoulos
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1302 - Safety of lorlatinib in subgroups of patients from a phase 1/2 trial
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract