Inclusion Criteria:
- Provision of signed and dated, written Informed consent form (ICF) prior to any
trial-specific procedures, sampling, or analyses
- Patients ≥18 years of age at the time of signature of the ICF
- Part I (dose escalation):
--Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic
solid tumours (any type)
- For whom no therapy of proven efficacy exists, or who are not amenable to
standard therapies.
- Must have measurable lesions according to Response Evaluation Criteria in Solid
Tumours (RECIST) v1.1
- Previous treatment with an anti-programmed cell death 1 (receptor) (PD-1)
monoclonal antibody (mAb) is allowed as long as the last administration of the
anti-PD-1 mAb on the previous treatment is a minimum of 60 days prior to starting
treatment in this trial.
- Part II (dose expansion):
- Patients must have measurable disease per RECIST v1.1 criteria, must have at
least 1 tumour lesion amenable to biopsy, and must be medically fit and willing
to undergo a biopsy before first treatment (if adequate archival tissue is not
available) and, unless clinically contraindicated, after 6 weeks on therapy.
- Dose Expansion Cohorts: Patients with a confirmed diagnosis of advanced,
unresectable, and/or metastatic solid tumours of one of the following types:
- Second and 3rd line Non-small cell lung cancer (NSCLC) patients:
- Must have progressed on anti-PD-1 or anti-programmed cell death ligand
1 (PD-L1) treatment after having achieved radiologically confirmed
benefit (minimum of stable disease)
- Must have had a minimum duration of benefit of 4 months and minimum
treatment duration of 2 months on the previous anti- PD-1 or anti-PD-L1
treatment without experiencing disease progression during that period.
- The anti-PD-1- or anti-PD-L1-containing treatment must have been the
latest treatment regimen prior to enrolling in this trial
- Must be within >4 and <12 weeks since the latest treatment and their
first dose in this trial. Patients who have had anti-PD-1 or anti-PD-L1
monotherapy as their first-line NSCLC treatment regimen must have a
PD-L1 expression level of ≥1% at baseline (local validated testing).
- Anti-PD-1 or anti-PD-L1 treatment-naïve patients with microsatellite stable
Metastatic colorectal Cancer (mCRC):
- Patients must have had ≥ 1 line treatment
- Must have microsatellite stable disease (identified using any validated
test)
- Must be anti-PD-1 and anti-PD-L1 treatment naïve
- Anti-PD-1 or anti-PD-L1 pretreated patients with any high Tumour mutational
burden (TMB) (≥10 mutations/Mb) and/or Microsatellite instability high
(MSI-H) and/or DNA MMRd solid tumours
- Patients must have high TMB (≥ 10 mutations/Mb) and/or MSI-H and/or DNA
mismatch repair deficient (MMRd) (measured using any validated test).
- Patients must have received 1 prior anti-PD-1 or anti-PD-L1 treatment
regimen.
- 1st-line squamous or non-squamous NSCLC patients:
- Patients must be treatment naïve
- Must be epidermal growth factor receptor (EGFR) and anaplastic lymphoma
kinase (ALK) wild type (only applicable to patients with non-squamous
NSCLC)
- Regardless of PD-L1 expression level. However, the number of patients
with high level of PD-L1 expression (≥50% PD-L1) will be limited to a
maximum of 10 patients
- Eastern Cooperative Oncology Group (ECOG, R01-0787) score: 0 to 1
- Life expectancy of at least 12 weeks after the start of the treatment according to the
Investigator's judgement
- 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.
Exclusion Criteria:
- Major surgery (major according to the Investigator's assessment) performed within 12
weeks prior to first trial treatment or planned within 12 months after screening,
e.g., hip replacement
- Patients who must or wish to continue the intake of restricted medications (see
Section 4.2.2.2) or any drug considered likely to interfere with the safe conduct of
the trial
- Previous enrolment in this trial
- Any investigational or anti-tumour treatment, except BI 754091, within 4 weeks or
within 5 half-life periods (whichever is shorter) prior to the initiation of trial
treatment.
- Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
starting study treatment with the exception of alopecia and Grade 2 neuropathy due to
prior platinum-based therapy
- Prior treatment with anti-Lymphocyte-activation gene 3 (LAG-3) agents
- Patients with NSCLC that has EGFR mutations or ALK rearrangements (only applicable to
patients with non-squamous NSCLC).
- Presence of other active invasive cancers other than the one treated in this trial
within 5 years prior to screening, with the exception of appropriately treated
basal-cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or other
local tumours considered cured by local treatment
- Untreated brain metastasis(es) that may be considered active. Patients with previously
treated brain metastases may participate provided they are stable (i.e., without
evidence of PD by imaging for at least 4 weeks prior to the first dose of trial
treatment, and any neurologic symptoms have returned to baseline), and there is no
evidence of new or enlarging brain metastases.
- Inadequate organ function or bone marrow reserve as demonstrated by the laboratory
values presented in Table 3.3.3: 1.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >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 known to prolong the 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,
multi-gated acquisition scan). 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
both.
- History of pneumonitis within the last 5 years
- History of severe hypersensitivity reactions to other mAbs
- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of study treatment.
- Active autoimmune disease or a documented history of autoimmune disease, except
vitiligo or resolved childhood asthma/atopy
- Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal
therapy) at start of treatment in this trial
- Known history of human immunodeficiency virus infection or an active hepatitis B or C
virus infection
- Interstitial lung disease
- Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion,
makes him/her an unreliable trial subject, unlikely to complete the trial, or unable
to comply with the protocol procedures.
