1030P - Phase I, first-in-human trial evaluating the STING agonist BI 1387446 alone and in combination with ezabenlimab in solid tumors

Background

Engagement of the STING pathway is involved in spontaneous and treatment-induced anti-cancer immunity. Activation of STING with a specific agonist, as a monotherapy or in combination with anti-PD1 therapy, may be a promising novel anticancer strategy. Here we report the first-in-human results for the STING agonist BI 1387446 alone (Arm A) and in combination with ezabenlimab (Arm B).

Methods

The phase 1, open-label, multicenter, dose-finding study 1426.1 (NCT04147234) evaluated BI 1387446 ± ezabenlimab in patients with advanced or metastatic solid tumors. In Arms A and B, BI 1387446 was given intratumorally starting at 50 μg (Cycles 1–3: Days 1, 8, 15; Cycle ≥4: Day 1). Patients in Arm B received ezabenlimab 240 mg intravenously on Day 1 in 21-day cycles. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Eligibility criteria included: ECOG PS 0 or 1, ≥1 lesion suitable for injection, and exhausted standard treatment options. Primary endpoint was maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs). Secondary and further endpoints included safety, efficacy, pharmacokinetics, and pharmacodynamics.

Results

Overall, 41 patients were treated (Arm A n=26; Arm B n=15). In Arm A, median age was 63 years and 46.2% had ECOG PS 1. In Arm B, median age was 56 years and 73.3% had ECOG PS 1. Maximum BI 1387446 dose was 400 μg in Arm A and 200 μg in Arm B. Median duration of BI 1387446 treatment was 1.8 months and 2.4 months in Arms A and B, respectively. DLTs were reported in 1 patient in Arm A receiving BI 1387446 200 μg (grade 3 fatigue and myalgia). No DLTs were reported in Arm B. The MTD was not reached. Safety and efficacy are summarized in the Table. Best response was stable disease (per RECIST v1.1 Arm A 46.2%, Arm B 53.3%).

Conclusions

BI 1387446 monotherapy and in combination with ezabenlimab was well tolerated. MTD for either regimen could not be determined. Table (334/600).

Table: 1030P

Clinical trial identification

NCT04147234.

Editorial acknowledgement

Medical writing support was provided by Bong-Akee Shey and Amber Wood at Meditech Media, Nucleus Global, and was funded by Boehringer Ingelheim Intl.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, TargImmune, T-knife, Chugai, Elevation Oncology, Ellipses Pharmacy, SyneosHealth, Genmab, Diaccurate; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Advisory Role: PsiOxus; Non-Financial Interests, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Member: ASCO, ESMO, SEOM, EORTC. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. V. Gambardella: Financial Interests, Personal, Advisory Board: Boehringer; Financial Interests, Institutional, Other, Research: Research Funding: Bayer, Boehringer, Roche; Financial Interests, Institutional, Other, Institutional: Institutional Funding: Genentech, Merck, Roche, Bayer, Lilly, Novartis, Takeda, AstraZeneca, BM. J. Thompson: Other, Institutional, Speaker’s Bureau: AstraZeneca. R. Latek: Financial Interests, Personal and Institutional, Other, Employee: Boehringer-Ingelheim Pharmaceutics, Inc. P. Sikken: Financial Interests, Institutional, Other, Employee: Boehringer-Ingelheim Pharmaceutics, Inc. M. Schmohl: Financial Interests, Institutional, Other, Employee: Boehringer-Ingelheim Pharma GmbH & Co KG . K.J. Harrington: Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim; Financial Interests, Institutional, Other: AstraZeneca. All other authors have declared no conflicts of interest.