The main objective of the dose-escalation parts of the trial is to determine the maximum
tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting
toxicities (DLTs), and/or the recommended dose for further development of BI 891065
monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety
and tolerability by monitoring the occurrence and severity of adverse events (AEs).
Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065
monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary
assessment of anti-tumour activity.
- Provision of signed and dated, written ICF in accordance with ICH-GCP and local
legislation prior to any trial-specific procedures, sampling, or analyses
- Patients ≥18 years-of-age at the time of signature of the ICF
- Male or female patients. Women of childbearing potential (WOCBP) and men able to
father a child must be ready and able to use highly effective methods of birth control
(that result in a low failure rate of less than 1% per year when used consistently and
correctly)during trial participation and for at least 6 months after the last
administration of trial medication. A list of contraception methods meeting these
criteria is provided in the patient information.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
- Life expectancy of at least 12 weeks after the start of the treatment according to the
- For Parts A and B: Patients with a confirmed diagnosis of advanced, unresectable
and/or metastatic solid tumours, who have failed standard treatment, or for whom no
therapy of proven efficacy exists, or who are not amenable to standard therapies.
Measurable lesions according to RECIST Version 1.1 must be present. Eligibility is
limited to the following tumour subtypes in Part B: bladder, colon, breast, Non-small
cell lung cancer (NSCLC), ovarian, pancreatic, renal, esophagogastric, sarcoma,
prostate, and melanoma.
- For Parts B and C: Patients must have measurable disease per RECIST v1.1, must have at
least 1 tumour lesion amenable to biopsy, and must be willing to undergo a biopsy
prior to first treatment and another biopsy while on therapy unless clinically
- For Part C: Patients with metastatic NSCLC who developed disease progression (per
RECIST v1.1) after the first scan (where SD, PR, or CR was demonstrated at the first
scan), and require new anti-cancer therapy after first line treatment with an anti
PD-1/anti PD-L1 mAb (given either as single agent therapy or in combination with a
platinum-based chemotherapy regimen).
- Major surgery (major according to the Investigator's and/or Medical Monitor's
assessment) performed within 12 weeks prior to randomization or planned within 12
months after screening (e.g., hip replacement)
- Presence of other active invasive cancers other than the one treated in this trial
within 5 years prior to screening, except appropriately treated basal cell carcinoma
of the skin, or in situ carcinoma of uterine cervix, or other local tumours considered
cured by local treatment
- Patients who must or wish to continue the intake of restricted medications or any drug
considered likely to interfere with the safe conduct of the trial
- Previous administration of BI 891065 or BI 754091
- Currently enrolled in another investigational device or drug trial, or less than 30
days since ending another investigational device or drug trial(s), or receiving other
- Patients who have been treated with any other anticancer drug within 4 weeks or within
5 half-life periods (whichever come earlier) prior to first administration of BI
891065. At least 7 days must have elapsed between the last dose of such agent and the
first dose of study drug.
- Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1
(except for alopecia and Grade 2 neuropathy due to prior platinum-based therapy)
- Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy
- Interstitial lung disease
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) >470 msec
- Any clinically important abnormalities (as assessed by the investigator) in
rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle
branch block, third degree heart block
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years-of-age, or
any concomitant medication with known or possible risk of QT interval
- Patients with an ejection fraction (EF) <55% or the lower limit of normal of the
institutional standard will be excluded. Only in cases where the Investigator (or
the treating physician or both) suspects cardiac disease with negative effect on
the EF, will the EF be measured during screening using an appropriate method
according to local standards to confirm eligibility (e.g., echocardiogram [ECHO],
multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than
6 months prior to first administration of study drug can be accepted provided
that there is clinical evidence that the EF value has not worsened since this
measurement in the opinion of the Investigator or of the treating physician or
- Out of range laboratory values are defined as:
- Alanine transaminase (ALT) and aspartate amino transferase (AST) >3 times the ULN
if no demonstrable liver metastases or >5 times ULN in the presence of liver
- Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who
are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN
- Human immunodeficiency virus (HIV) infection, acute or chronic viral hepatitis
- Known hypersensitivity to the trial drugs or their excipients
- Serious concomitant disease or medical condition affecting compliance with trial
requirements or which are considered relevant for the evaluation of the efficacy or
safety of the trial drug, such as cardiac, neurologic, psychiatric, infectious disease
or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may
increase the risk associated with trial participation or trial drug administration,
and in the judgment of the Investigator and/or Medical Monitor would make the patient
inappropriate for entry into the trial.
- Chronic alcohol or drug abuse or any condition that, in the Investigator's and/or
Medical Monitor's opinion, makes them an unreliable trial patient or unlikely to
complete the trial
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial and
for at least 6 months after the last administration of trial medication.
- Men who plan to father a child while in the trial and for at least 6 months after the
last administration of trial medication.
- Known presence of symptomatic central nervous system (CNS) metastases, unless
asymptomatic and off corticosteroids and/or anti-convulsant therapy for at least 2
weeks prior start of treatment. Patients with asymptomatic CNS metastases may be
enrolled following a 2-week washout period.
- Patients receiving systemic treatment with any immunosuppressive medication within 1
week prior treatment start (steroids of max. 10 mg prednisolone equivalent per day are
allowed, topical and inhaled steroids are not considered as immunosuppressive).
- For Parts A and B: Patients with known epidermal growth factor receptor (EGFR), known
anaplastic lymphoma kinase (ALK), or known ROS Proto-Oncogene 1 (ROS1) genomic tumour
aberrations, unless disease has progressed following available EGFR or ALK targeted
therapy (including osimertinib for EGFR T790M-mutated NSCLC)
- Out of range lab values as defined:
- Absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm3)
- Platelet (PLT) count <100 x 109/L
- Haemoglobin <90 g/L (<9 g/dL)
-- Creatinine >1.5 times ULN (patients may enter if creatinine is >1.5 x ULN and
estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2) (Chronic Kidney
Disease Epidemiology [CKD-EPI] Collaboration equation); confirmation of eGRF is only
required when creatinine is >1.5 X ULN.
- For Part C: Patients with EGFR, ALK, or (if known) ROS1 genomic tumor aberrations
- For Part C: Patients with any CTLA-4 therapy
- For Part C: One or more lines of anti-cancer therapy between previous
anti-PD-1/anti-PDL1 mAb therapy and study entry.