An open label, randomized Phase II study of BI 754091 alone or in combination with BI 836880 in patients with chemotherapy resistant, unresectable, metastatic squamous cell carcinoma of the anal canal

1) Signed and dated written Informed Consent Form (ICF) in accordance with
ICH-GCP and local legislation prior to admission to the trial.
2) 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 ICF.
3) Patients must have histologically or cytologically documented surgically
unresectable
locally-advanced or metastatic SCCA.
4) Patients with loco-regional anal cancer as initial diagnosis must have
unresectable
progressive locally advanced or metastatic SCCA after failure of at least one
line (but
not more than two lines) of previous systemic treatment unless ineligible for or
intolerant to this systemic therapy.
Note 1: the primary treatment (chemoradiotherapy) for loco-regional disease is
not
considered as a previous line of systemic treatment
Note 2: If palliative radiotherapy was given, this radiotherapy must have been
completed at least 30 days prior to the start of the trial treatment and lesions
previously receiving palliative radiotherapy must not be selected as target
lesions for
RECIST 1.1 evaluation during this trial.
Patients with metastatic anal cancer as initial diagnosis (no prior treatment
for
loco-regional cancer) must have failed one line of previous systemic treatment
(chemotherapy ± radiotherapy) for the metastatic anal cancer unless ineligible
for or
intolerant to this systemic treatment. (Patients with metastatic anal cancer as
initial
diagnosis who have received two or more lines of systemic treatment for the
metastatic
anal cancer are not eligible for the study.)
5) All patients must have at least one measurable lesion according to RECIST
v1.1
criteria.
6) Eastern Cooperative Oncology Group performance status [ECOG, R01-0787]
score 0 to 1
7) All patients must be willing to undergo blood testing for human
immunodeficiency
virus (HIV) presence in the blood if not tested within the past 6 months prior
to
signature of ICF for this trial.
For patients confirmed as HIV positive, all of the following (a-d) applies:
a) CD4+ count * 250 cells/*L
b) Undetectable viral load (local lab assessment)
c) Must be currently receiving Highly Active Antiretroviral Therapy
d) A HIV/Infectious Diseases specialist must be consulted or patient must be
under
the care of the HIV/Infectious Diseases specialist
8) Patients must be willing to allow PD-L1 status assessment by one of
following options.
Preference is given to fresh tumour biopsy sample collection at baseline before
receiving first trial medication. In case a fresh tumour biopsy cannot be
obtained (e.g.
inaccessible lesions or patient safety concern), archival tissue will be
requested. If
neither is available any previous historical information regarding PD-L1 status
should
be collected via eCRF. Exceptions may be considered after consultation with and
approval by the Sponsor.
9) Male or female patients. Women of childbearing potential (WOCBP)1 and men
able to
father a child must be ready and able to use highly effective methods of birth
control
Boehringer Ingelheim 29 Apr 2020
BI Trial No.: 1381-0011
c29383028-03 Clinical Trial Protocol Page 37 of 127
Proprietary confidential information © 2020 Boehringer Ingelheim International
GmbH or one or more of its affiliated companies
001-MCS-40-106_RD-03 (18.0) / Saved on: 10 Jul 2019
per ICH M3 (R2) that result in a low failure rate of less than 1% per year when
used
consistently and correctly, for the entire duration of the trial treatment
intake and for 6
months after the end of the trial treatment. A list of contraception methods
meeting
these criteria is provided in the patient information. For further detail refer
to Section
4.2.2.3 and FlowChart

- Current or prior treatment with any systemic anti-cancer therapy or any
investigational product (or device) either within 28 days or less than 5
half-lives (whichever is shorter) before start of trial treatment.
- Major injuries and/or surgery or bone fracture within 4 weeks of start of
treatment, or planned surgical procedures during the trial period.
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled
hypertension, unstable angina, history of infarction within past 6 months,
congestive heart failure > NYHA II).
- Known inherited predisposition to bleeding or to thrombosis in the opinion of
the investigator.
- History of severe hemorrhagic or thromboembolic event in the past 12 months
(excluding central venous catheter thrombosis and peripheral deep vein
thrombosis).
- Patients who require full-dose anticoagulation (according to local
guidelines). No Vitamin K antagonist and other anticoagulation allowed; LMWH
and acetylsalicylic acid (ASA) allowed only for prevention not for curative
treatment.
- Prior treatment with anti-PD-1, anti-PD-L1, or anti CTLA-4 treatment
- Prior treatment with any antiangiogenic agent (e.g. bevacizumab, cediranib,
aflibercept, vandetanib, XL-184, sunitinib, etc.)
- Further criteria apply.