533MO - Phase Ib study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody: Initial results in patients (pts) with solid tumours

Background

Preclinical studies have shown that combining anti-VEGF/Ang2 with anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell-mediated tumour cell destruction. BI 836880 is a humanized bispecific nanobody® that targets VEGF and Ang2, and BI 754091 is an anti-PD-1 antibody. Dose-finding trials of BI 836880 and BI 754091 in advanced solid tumours determined the recommended phase II dose (RP2D) for monotherapy as 720 mg q3w and 240 mg q3w, respectively. Here, we report results from a phase Ib study assessing BI 836880 in combination with BI 754091.

Methods

In part 1 (dose escalation), pts with locally advanced or metastatic (m) non-squamous NSCLC who progressed during/after completion of ≥2 cycles of platinum-based chemotherapy (CT) ± a checkpoint inhibitor (CPI) received BI 836880 plus fixed-dose BI 754091. RP2D was determined as BI 836880 720 mg plus BI 754091 240 mg q3w. In Part 2 (expansion phase), patients are recruited to one of 7 cohorts: mNSCLC after CPI monotherapy; mNSCLC after CT + CPI; mSCLC after CT ± CPI; immunotherapy-resistant m-melanoma; recurrent glioblastoma after 1st-line CT; HCC after prior sorafenib or lenvatinib; and previously untreated/unresectable HCC.

Results

At data cut-off (April 2020), 18 pts had received BI 836880 plus BI 754091 (14 in Part 1, 4 in Part 2); 11 males; median age 59 years, 13 had received prior CPI. Seven pts remain on treatment (including 1 treated for >12 months). 16 pts experienced an adverse event (AE; any-cause), most commonly (all%/G3%) hypertension (50/28), asthenia (33/6), vomiting, nausea and cough (each 33/0). No G4 AEs were reported; 2 G5 AEs occurred (1 general physical health deterioration and 1 tracheal haemorrhage). 6 pts had immune-related AEs (including G2 hypothyroidism; G2 pruritus, G2 vomiting, G1 papular rash). To date, 3 pts have achieved confirmed partial response (two NSCLC pts in Part 1, one 2^nd-line HCC pt in Part 2), 10 pts had stable disease, 3 had progressive disease; data were not available for 2 pts.

Conclusions

The combination of BI 836880 and BI 754091 had a manageable safety profile, and preliminary antitumor activity was observed. Expansion cohorts are ongoing.

Clinical trial identification

NCT03468426.

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Jane Saunders, of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the development of this abstract.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

N. Girard: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda; Advisory/Consultancy: GSK; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Pharmamar; Travel/Accommodation/Expenses: MSD Oncology. M. Wermke: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self): Merck; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Kite Pharma; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Heidelberg Pharma; Travel/Accommodation/Expenses: Glenmark. F. Barlesi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Merck Serono; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy: Merck; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): ACEA Bioscience; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Eisai. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma; Research grant/Funding (institution): AstraZenca/Medimmune; Research grant/Funding (institution): Boehringer-Ingelheim; Research grant/Funding (institution): Hanmi; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merus; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): ONO Pharmaceutical; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): TP Therapeutics; Research grant/Funding (institution): Xcovery; Research grant/Funding (institution): Yuhan; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Daiichi Sankyo. F. Ghiringhelli: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Astra; Honoraria (self): Merck Serono; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Bayer; Honoraria (self), Travel/Accommodation/Expenses: Servier. H.T. Landsteiner: Full/Part-time employment: Boehringer Ingelheim. G. Jayadeva: Full/Part-time employment: Boehringer Ingelheim. J. Alt: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Takeda. B. Hackanson: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Takeda; Honoraria (self): Pfizer.