Inclusion Criteria
Master Protocol:
- Provision of signed and dated, written Master informed consent form (ICF) prior to any
trial-specific procedures, sampling, or analyses.
- Patient ≥18 years of age at the time of signature of the ICF.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1.
- Patient must agree to a pre-treatment biopsy (if archival tissue is not available) and
on-treatment tumour biopsy.
- 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 willing 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.
Module A:
- Histologically confirmed diagnosis of one of the following cohorts:
- Cohort 1 GEC - Locally advanced, unresectable or metastatic gastric adenocarcinoma or
gastro oesophageal adenocarcinoma (GEC) (defined as primary tumour localisation below
the gastro oesophageal junction (GEJ) with prior anti-PD-1 or anti-PD-L1 based treated
tumour.
- Cohort 2 Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy:
Any advanced or metastatic solid tumour with previously anti-PD-1 or anti-PD-L1 based
treatment who progressed after achieving benefit
- Cohort 3 Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy:
Select advanced or metastatic solid tumour types with previous anti-PD- 1/PD-L1 based
treated tumour without achieving benefit.
- All patients must have measurable lesions according to RECIST v1.1
- Patient must agree to pre- and on-treatment tumour biopsies. If archived tumour tissue
is available from the last treatment failure, sections may be supplied instead of a
pre-treatment biopsy.
Module C:
- Histologically confirmed diagnosis of one of the following cohorts:
- Cohort 1: GEC: Locally advanced, unresectable or metastatic gastric
adenocarcinoma or GEC.
- Cohort 2: Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based
therapy: Any advanced or metastatic solid tumour (excluding NSCLC and melanoma)
with previously anti-PD-1 or anti-PD-L1 based treatment which progressed after
achieving benefit.
- Cohort 3: Patients with primary resistance to anti-PD-1 or anti-PD-L1 based
therapy: Select advanced or metastatic solid tumour types with previous
anti-PD-1/PD-L1 based treated tumour without achieving benefit.
- Cohort 4: Locally advanced, unresectable or metastatic second line or greater,
microsatellite stable (MSS) colorectal cancer.
- Cohort 5: Advanced Endometrial cancer: Endometrial carcinoma that is pMMR
(Mismatch Repair-Proficient)/MSS and is advanced, recurrent, or persistent and
has relapsed or is refractory to curative therapy.
- All patients must have at least one measurable lesion according to RECIST v1.1
- Further inclusion criteria apply
Exclusion Criteria
Master Protocol:
- Any investigational treatment anti-tumour treatment within 4 weeks or within 5
half-life periods (whichever is shorter) prior to the initiation of trial treatment.
- More than one anti-PD-(L)1-based treatment regimen prior to entering study
- 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.
- Known history of severe hypersensitivity reactions to other mAbs or known
hypersensitivity to the trial drugs or their excipients.
- Presence of central nervous system (CNS) metastases, unless treated and asymptomatic
and off corticosteroids and/or anticonvulsant therapy for at least 2 weeks prior to
start of treatment.
- 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. Patients who were permanently
discontinued from previous anti-PD-1 or anti-PD-L1 therapy because of a immune-related
adverse event (irAE).
Module A:
- Previous treatment with an anti-LAG-3 Agent
Module C:
- Unresolved, Grade >1 toxicity before the start of treatment with the study drug except
for hair loss (alopecia) and hypothyroidism that requires thyroid hormone supplements
but is asymptomatic under therapy.
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension,
unstable angina, history of infarction within past 6 months, congestive heart failure
> New York Heart Association [NYHA] II)
- History of severe haemorrhagic or thromboembolic event in the past 12 months
- Known inherited predisposition to bleeding or to thrombosis, in the opinion of the
investigator - Further exclusion criteria apply