Abstract 1030P
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
Arm A n=26 | Arm B n=15 | |
AEs, n (%) | ||
Any | 25 (96.2) | 15 (100) |
Immune-related | 1 (3.8) | 0 |
DLTs | 1 (3.8) | 0 |
Leading to BI 1387446 dose reduction | 0 | 0 |
Leading to BI 1387446 discontinuation | 1 (3.8) | 2 (13.3) |
BI 1387446-related AEs, n (%) | ||
Any grade | 14 (53.8) | 9 (60.0) |
Injection site pain | 4 (15.4) | 0 |
Fatigue | 3 (11.5) | 1 (6.7) |
Pyrexia | 3 (11.5) | 1 (6.7) |
Asthenia | 1 (3.8) | 4 (26.7) |
Hyperthyroidism | 0 | 1 (6.7) |
Grade 3 | 3 (11.5) | 0 |
Grade 4 or 5 | 0 | 0 |
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.
Resources from the same session
1343P - Amivantimab as a salvage strategy post TKI (osimertinib/mobocertinib) in EGFRm NSCLC
Presenter: Bilal Krayim
Session: Poster session 19
1344P - A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC)
Presenter: Jorge Nieva
Session: Poster session 19
1345P - Preclinical activity of ORIC-114, a highly selective, brain penetrant, irreversible kinase inhibitor, against atypical mutations in EGFR
Presenter: Melissa Junttila
Session: Poster session 19
1346P - Efficacy and safety of high dose furmonertinib combined with intrathecal injection in EGFR-mutated advanced NSCLC patients with LM progressed on osimertinib
Presenter: Xiaoyan Li
Session: Poster session 19
1348P - Management of paresthesia in patients treated with lazertinib: Integrated analysis of LASER201 and LASER301 studies
Presenter: Yun-Gyoo Lee
Session: Poster session 19
1349P - Continuing osimertinib in combination with chemotherapy after osimertinib failure reduces CNS progression in patients with EGFR-mutated NSCLC and CNS metastases
Presenter: Molly Li
Session: Poster session 19
1350P - Survival benefits of local treatment (LT) for brain metastases (BMs) in patients (pts) with EGFR-mutant non-small cell lung cancer (EGFR-mt NSCLC) treated with osimertinib
Presenter: Takehiro Tozuka
Session: Poster session 19
1351P - Efficacy of early stereotactic body radiotherapy to the primary lung lesion in patients with NSCLC harboring sensitive EGFR mutations treated with first-line EGFR-TKIs
Presenter: Dan Tao
Session: Poster session 19
1352P - Plasma metabolic signatures uncover therapeutic response and prognosis of third-generation EGFR-TKI treatment in patients with NSCLC
Presenter: Ruyun Gao
Session: Poster session 19