A study to test different doses of BI 836880 combined with ezabenlimab in patients with advanced non-small cell lung cancer followed by other types of advanced solid tumours

JRCT ID: jRCT2031200207

Registered date:18/11/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: advanced solid tumours
• Date of first enrollment: 08/03/2021
• Target sample size: 6
• Countries of recruitment: Australia,Japan,China,Japan,France,Japan,Germany,Japan,Hong Kong,Japan,Korea,Japan,Poland,Japan,Russian,Japan,Spain,Japan,Taiwan,Japan,Ukraine,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional
• Intervention(s): i.v. infusion of each 3-week cycle with BI836880 and ezabenlimab

Outcome(s)

• Primary Outcome: the shrinkage estimator of objective response(OR) based on BHM

Secondary Outcome

-Adverse events (AEs), drug related AEs, drug related AEs leading to dose reduction or discontinuation during treatment period
-Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) (RANO for GBM and RECIST1.1 for all other cohorts) from first treatment infusion until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, lost to follow-up or withdrawal of consent.
-Duration of objective response (DoR), defined as the time from first documented CR or PR (RANO for GBM and RECIST1.1 for all other cohorts) until the earliest of disease progression or death among patients with OR.
-Progression-free survival (PFS) (RANO for GBM and RECIST1.1 for all other cohorts), defined as the time from first treatment infusion until disease progression or death from any cause, whichever occurs earlier.
-Tumour shrinkage (in millimeters), defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions in case of RECIST. In GBM, using RANO criteria, tumor shrinkage will be calculated based on the difference between the post-baseline and baseline measurements of the sum of product of the largest bi-dimensional measurements for all target lesions.
-Pharmacokinetic parameters Cmax, tmax, AUC0-504h after the first and fourth infusion cycle.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Of full age (according to local legislation, usually >= 18 years) at screening
2.At least one measurable target lesion outside the brain (excluding the glioblastoma patients), that can be accurately measured per RECIST v 1.1
3.ECOG performance status <= 1 (Karnofsky status for GBM)
4.Adequate hepatic, renal and bone marrow functions
5.Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression on or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen obtained up to 6 months prior to cycle 1, visit 1 (C1V1) may be submitted in case no systemic antineoplastic therapy has been administered between the biopsy and C1V1 (except for cohort D). For cohorts E, F and G, a fresh on-treatment biopsy is mandatory at C3D1, if possible from the same lesion as the pre-treatment biopsy.
6.Life expectancy >= 3 months after start of the treatment in the opinion of the investigator

Exclude criteria

1.Not more than one CPI based treatment regimen prior to entering study (eg. anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibody) unless combination CPIs approved by the local regulatory agencies; For eg., Melanoma cohort (Cohort E)
2.Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (exception for patients in HCC cohorts; Cohort F & cohort G).
3.Prior treatment with any antiangiogenic treatment (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc) except for sorafenib and lenvatinib in 2nd line HCC cohort (Cohort F).
4.Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening

Further exclusion criteria:

Exclusion criteria for Glioblastoma:
5.Tumor primarily localized to the brainstem or spinal cord.
6.Presence of diffuse leptomeningeal disease or extracranial disease.
7.Is known to have IDH mutant variety of recurrent glioblastoma.
8.Any prior treatment with prolifeprospan 20 with carmustine wafer.
9.Any prior treatment with an intracerebral agent.

Exclusion criteria for Melanoma cohort:
10.Uveal or ocular melanoma

Exclusion criteria for HCC cohorts (Cohorts F & G):
11.Co-infection with HBV and HCV or HBV and hepatitis D virus (HDV)
12. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
13.History of hepatic encephalopathy
14.Untreated or incompletely treated varices with bleeding or high-risk for bleeding
15. Untreated active Hepatitis B virus (HBV)
16. Treatment with any HCV anti-viral therapy within 4 weeks prior to Cycle 1 Day 1

Related Information

• Primary Sponsor: Yamagami Tomohiro
• Secondary ID(s): NCT03468426