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
2935 - Correlation of progression free survival-2 and overall survival in solid tumors
Presenter: Paul Mainwaring
Session: Poster Display session 1
Resources:
Abstract
2273 - High performance of serial tumor biopsies in first in human (FIH) phase I trials.
Presenter: Jun Sato
Session: Poster Display session 1
Resources:
Abstract
5933 - Response rates and lesion-level progression patterns of solid tumor patients in an academic phase 1 program: implications for tumor heterogeneity
Presenter: Christopher Chen
Session: Poster Display session 1
Resources:
Abstract
3569 - Clinical Benefit and Response Rate in Early Phase Clinical Trials: First Report from a Single-Institution Study
Presenter: Antonio Marra
Session: Poster Display session 1
Resources:
Abstract
4139 - Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): a single Phase I Unit experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
4451 - Improving patient selection for immuno-oncology phase 1 trials: an external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O).
Presenter: Ghassan Al Darazi
Session: Poster Display session 1
Resources:
Abstract
1696 - Demonstrating the Changing Trends in Phase 1 Clinical Trials
Presenter: Christina Guo
Session: Poster Display session 1
Resources:
Abstract
3202 - Participation of Women in phase 1 oncology clinical trials
Presenter: Laura Vidal
Session: Poster Display session 1
Resources:
Abstract
4518 - Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials
Presenter: Joeri Douma
Session: Poster Display session 1
Resources:
Abstract
4368 - Safety of Tumor Treating Fields delivery to the torso: Meta analysis from TTFields clinical trials
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract