BI13181-0011: This phase II trial is trying to assess how well a form of targeted therapy works for the treatment of advanced anal cancer that has spread to other parts of the body and has progressed on or after chemotherapyAn 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

Inclusion

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 Squamous cell carcinoma of the anal canal (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.

   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 (ECOG) performance status 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:

   1. CD4+ count ≥ 250 cells/μL
   2. Undetectable viral load (local lab assessment)
   3. Must be currently receiving Highly Active Antiretroviral Therapy
   4. 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 programmed cell death ligand 1 (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) and men able to father a child must be ready and able to use highly effective methods of birth control 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.