A Study to Test How Different Doses of BI 1703880 in Combination With Ezabenlimab Are Tolerated in People With Different Types of Advanced Cancer (Solid Tumours)

Official title

Phase Ia, First in Human Open Label Dose Escalation Trial Evaluating Intravenous BI 1703880 in Combination With Intravenous Ezabenlimab for Treatment of Advanced Solid Tumours

Overview

This study is open to adults with different types of advanced cancer. People can take part if previous treatment was not successful, or no treatment exists. The purpose of this study is to find the highest dose of a medicine called BI 1703880 that people with advanced cancer can tolerate when taken together with ezabenlimab. BI 1703880 and ezabenlimab are medicines that may help the immune system fight cancer. In this study, BI 1703880 is given to people for the first time. Participants get BI 1703880 and ezabenlimab as infusions into a vein. During the first 6 weeks, they get BI 1703880 once a week. Later, they get BI 1703880 every 3 weeks. After the first 3 weeks, they get ezabenlimab in addition every 3 weeks. Participants can get BI 1703880 for up to 1 year and ezabenlimab for up to 2 years as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. At these visits, the doctors check participants' health and take note of any unwanted effects.

Interventions

• Drug BI 1703880
  BI 1703880
• Drug Ezabenlimab
  Ezabenlimab

Primary outcome measures

• Occurrence of dose limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period [Time frame: up to 6 weeks]

Secondary outcome measures (3)

• Occurrence of DLTs during the on-treatment period [Time frame: up to 804 days]
• Maximum measured concentration of BI 1703880 in plasma (Cmax) [Time frame: up to 804 days]
• Area under the concentration-time curve of BI 1703880 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) [Time frame: up to 804 days]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic or relapsed/refractory solid tumour. Patient must have at least one measurable lesion (according to Response Criteria in Solid Tumours (RECIST 1.1)).
• Patient must have exhausted or refused established treatment options for the malignant disease, or is not eligible for established treatment options.
• Has a lesion amenable to pre-treatment and on-treatment biopsy and patient consents to both biopsies.
• Medically fit and willing to undergo all mandatory trial procedures.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate organ function or bone marrow reserve as demonstrated at screening by the following laboratory values:

• Absolute neutrophil count ≥ 1.5x10\^9/L (≥ 1.5x10\^3/μL, ≥ 1500/mm3); platelet count ≥ 100x10\^9/L (≥ 100x10\^3/μL, ≥ 100x10\^3/mm3), without the use of hematopoietic growth factors within 4 weeks of start of trial medication
• Haemoglobin ≥ 90 g/L (≥ 9.0 g/dL, ≥ 5.6 mmol/L)
• Estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73m\^2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases.
• Total bilirubin ≤ 1.5 x ULN, except for patients with Gilbert's syndrome: total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
• partial thromboplastin time (PTT) / activated partial thromboplastin time (aPTT) <1.5 x ULN
• Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF).
• Signed and dated written ICF in accordance with International Council for Harmonisation- Good Clinical Practice (ICH-GCP) and local legislation, obtained before performing any protocol related procedures that are not part of normal standard of practice care. Note: If a patient declines to participate in the voluntary biobanking component of the trial, he/she will not be excluded from other aspects of the trial.

Further inclusion criteria apply

Exclusion criteria

• Any investigational or antitumour treatment within 4 weeks or 5 half-life periods prior to the first treatment whichever is shorter.
• Prior STING agonist therapy.
• Prior intolerability of a anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy.
• History of allergy or hypersensitivity to study agent components.
• Immunosuppressive therapies including, but not limited to, systemic corticosteroids at doses exceeding >10 mg/day of prednisone or equivalent, and tumour necrosis factor-alpha blockers.
• Persistent toxicity from previous treatments (including immune related Adverse Events (irAEs)) that has not resolved to Grade ≤1, except for alopecia, xerostomia, and immunotherapy related endocrinopathies.
• Evidence of active, non-treatment related autoimmune disease, except for endocrinopathies.
• History or complication of pneumonitis or interstitial lung disease within the last 12 months, or any prior pneumonitis related to immunotherapy.

Further exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 4 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• CIO Clara Campal — Madrid
• Instituto Valenciano de Oncología — Valencia
• Hospital Clinico Universitario de Valencia — Valencia

United States · 3 centers

• Valkyrie Clinical Trials — Los Angeles
• Yale University School of Medicine — New Haven
• John Theurer Cancer Center — Hackensack

Japan · 3 centers

• National Cancer Center Hospital East — Chiba, Kashiwa
• Saitama Medical University International Medical Center — Saitama, Hidaka
• Japanese Foundation for Cancer Research — Tokyo, Koto-ku

United Kingdom · 3 centers

• The Royal Marsden Hospital, Chelsea — London
• Churchill Hospital — Oxford
• The Royal Marsden Hospital, Sutton — Sutton

Publications

• Harrington K, Kitano S, Gambardella V, Parkes EE, Moreno I, Alonso G, Doi T, Berz D, Gutierrez ME, Fernandez N, Schmohl M, Barrueco J, LoRusso P. Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors. Future Oncol. 2025 Jan;21(2):195-200. doi: 10.1080/14796694.2024.2441107. Epub 2025 Jan 16. PMID 39817655

Identifiers

NCT: NCT05471856 · 1480-0001 · 2022-000298-22 · U1111-1303-5359 · 2024-511501-37-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗