Abstract 2451
Background
Preclinical evidence shows that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) promote an immunosuppressive state in the tumour microenvironment, and that the combination of anti-VEGF/Ang2 with anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell mediated tumour cell killing. BI 836880, a humanised bispecific nanobody that targets VEGF and Ang2, and BI 754091, an anti-PD-1 antibody, have shown safety and preliminary antitumour activity as monotherapies in phase I studies (RP2D, 720 mg iv q3w for BI 836880 and 240 mg iv q3w for BI 754091). The safety and efficacy of BI 836880 + BI 754091 are being assessed in this phase Ib trial in patients (pts) with advanced solid tumours.
Trial design
This open-label, dose-escalation/cohort-expansion trial is being conducted in two parts: Part 1, dose escalation of BI 836880 with BI 754091 in pts with advanced/metastatic, PD-L1 positive, nonsquamous NSCLC; Part 2, exploratory expansion cohorts (A–F) in 6 pt populations (A: metastatic [m] NSCLC after checkpoint inhibitor [CPI] monotherapy; B: mNSCLC after chemotherapy [CTX] + CPI; C: mSCLC after CTX with/without CPI; D: immunotherapy-resistant m-melanoma; E: recurrent glioblastoma after 1st line CTX; F: hepatocellular carcinoma after prior sorafenib or lenvatinib with/without subsequent CPI therapy). In Part 1, pts will receive BI 836880 (cohorts of 360, 500 and 720 mg iv q3w) + fixed-dose BI 754091 240 mg iv q3w, following a Bayesian logistic regression model with overdose control, with oversight from a safety monitoring committee. The primary endpoint in Part 1 is the MTD/RP2D, based on DLTs in Cycle 1. In Part 2, pts will receive BI 836880 at the RP2D + BI 754091 240 mg iv q3w. The primary endpoint in Part 2 is objective response; secondary endpoints are disease control, duration of response, PFS and tumour shrinkage. Safety, PK and exploratory biomarkers will be assessed. ∼220 pts will enroll globally: 20–25 pts in Part 1 and ∼200 in Part 2 (40 in Cohorts A/B; 30 in Cohorts C–F). As of May 2019, 6 pts have been treated in Part 1. Part 2 will begin once the RP2D is established in Part 1. Updates will be presented.
Clinical trial identification
NCT03468426.
Editorial acknowledgement
Fiona Scott, PhD, of GeoMed, an Ashfield company, part of UDG Healthcare plc; supported financially by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim GmbH & Co, Ingelheim, Germany.
Disclosure
N. Girard: Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: BMS; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: Boehringer; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee: MSD; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: Roche; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: AstraZeneca. B. Hackanson: Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche. M. Wermke: Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self): Glenmark; Honoraria (self): Kite; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Gemoab. F. Barlesi: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Boehringer–Ingelheim; Honoraria (self), Honoraria (institution): Eli Lilly Oncology; Honoraria (self), Honoraria (institution): F. Hoffmann–La Roche Ltd; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Merck; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Pierre Fabre; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Takeda; Honoraria (institution): AbbVie; Honoraria (institution): ACEA; Honoraria (institution): Amgen; Honoraria (institution): Bayer; Honoraria (institution): Eisai; Honoraria (institution): Genentech; Honoraria (institution): Ipsen; Honoraria (institution): Ignyta; Honoraria (institution): Innate Pharma; Honoraria (institution): Loxo; Honoraria (institution): MedImmune; Honoraria (institution): Sanofi-Aventis. H.T. Landsteiner: Full / Part-time employment: Boehringer Ingelheim . G. Jayadeva: Full / Part-time employment: Boehringer Ingelheim. J. Alt: Advisory / Consultancy, Consulting fee: Boehringer Ingelheim.
Resources from the same session
3020 - Circulating tumor DNA (ctDNA) analysis depicts mechanisms of resistance and tumor response to BRAF inhibitors in BRAF-mutant non-small cell lung cancer (NSCLC)
Presenter: Sandra Ortiz - Cuaran
Session: Poster Display session 1
Resources:
Abstract
1271 - A large scale prospective concordance study of oncogene driver detection between plasma- and tissue-based NGS analysis in advanced non-small cell lung cancer (NSCLC).
Presenter: Ryo Itotani
Session: Poster Display session 1
Resources:
Abstract
1132 - Biomarker status as a mediator of age-related overall survival (OS) in advanced non-small cell lung cancer (aNSCLC)
Presenter: Aaron Cohen
Session: Poster Display session 1
Resources:
Abstract
1502 - An exploratory analysis of on-treatment ctDNA measurement as a potential surrogate for overall survival for atezolizumab benefit in the OAK Study
Presenter: David Gandara
Session: Poster Display session 1
Resources:
Abstract
3912 - Disease monitoring of EGFR mutation-positive NSCLC patients via circulating tumor DNA
Presenter: Wei Fang Hsu
Session: Poster Display session 1
Resources:
Abstract
3856 - Incidence of T790M in NSCLC patients progressed to gefitinib, erlotinib, and afatinib: a study on circulating tumor DNA
Presenter: Romano Danesi
Session: Poster Display session 1
Resources:
Abstract
1330 - Folate receptor-positive circulating tumor cells as a predictive biomarker for the efficacy of first-line pemetrexed-based therapy in patients with non-squamous non-small cell lung cancer
Presenter: Xiaoxia Chen
Session: Poster Display session 1
Resources:
Abstract
3512 - Carcinoembryonic Antigen of Cerebrospinal Fluid Predict Prognosis of Leptomeningeal Metastasis from Non-Small Cell Lung Cancer
Presenter: Junjie Zhen
Session: Poster Display session 1
Resources:
Abstract
3852 - Liquid biopsy in clinical pratice of Non-Small-Cell-Lung Cancer (NSCLC): a multi-institutional experience
Presenter: Giovanna De Maglio
Session: Poster Display session 1
Resources:
Abstract
1205 - A Phase III Study Comparing SB8, a Proposed Bevacizumab Biosimilar, and Reference Bevacizumab in Patients with Metastatic or Recurrent Non-squamous NSCLC
Presenter: Martin Reck
Session: Poster Display session 1
Resources:
Abstract