BI 905711

P1, N=13, Completed, Boehringer Ingelheim | Terminated --> Completed

P1, N=110, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

P1, N=13, Terminated, Boehringer Ingelheim | Phase classification: P1a/1b --> P1 | Trial completion date: Mar 2024 --> Oct 2023 | Active, not recruiting --> Terminated; Company decision

P1, N=110, Active, not recruiting, Boehringer Ingelheim | Trial primary completion date: Jan 2024 --> Jul 2023

P1a/1b, N=13, Active, not recruiting, Boehringer Ingelheim | Trial primary completion date: Mar 2024 --> Oct 2023

In heavily pretreated pts, BI 905711 was associated with a tolerable safety profile and early signs of disease control. BI 905711 will be further assessed in Phase Ib in 4 dose groups: 0.6/1.2/2.4 mg/kg every 14 days, and 0.6 mg/kg weekly. Clinical trial information: NCT04137289.

This Phase Ia/Ib, open-label, multicenter study (NCT05087992) aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), and efficacy of BI 905711 with CT (FOLFIRI; irinotecan, leucovorin, and fluorouracil) ± bevacizumab (BEV) in pts with advanced GI cancers...In the CRC cohort, pts with prior progression on oxaliplatin-based therapy will be randomized 2:1 to receive FOLFIRI and BEV ± BI 905711. In the PDAC cohort, pts with CDH17+ PDAC with prior progression on gemcitabine-based first-line therapy will receive FOLFIRI + BI 905711...The study is ongoing. Clinical trial information: NCT05087992.

Conclusions BI 905711 showed a tolerable safety profile with favourable PK properties. Early signs of disease control in these heavily pretreated pts was observed and will be further assessed in phase Ib in 4 dose groups: 0.6/1.2/2.4 mg/kg every 14 days, and 0.6 mg/kg weekly.

No abstract available

In preclinical assays, BI 905711 demonstrated a potency shift of ̃1000 fold versus the 1st-generation TRAILR2 agonist lexatumumab. Secondary endpoints include PK parameters and OR in pts with measurable disease (phase Ia), and disease control, tumor shrinkage, duration of response, and progression-free survival (phase Ib). Trial enrollment is ongoing, with 33 pts enrolled to date.

Responders to BI 905711 were identified primarily within the classical and quasi-basal/hybrid subtypes when TRAILR2 was adequately co-expressed. This correlates with an enrichment pattern of CDH17 gene expression that is mostly within the classical gene cluster and strongly anti-correlated with basal-like cluster enrichment.Robust preclinical anti-tumor activity of BI 905711 in TRAILR2 and CDH17-expressing PDAC PDX models, along with this antibody’s potential for a favorable safety profile, has justified the enrollment of pancreatic cancer patients in the ongoing BI 905711 FIH Phase I clinical trial (NCT04137289).