A Study of BI 853520 in Patients With Various Types of Advanced or Metastatic Cancer

An Open Label Phase I Dose Finding Study of BI 853520 Administered Orally in a Continuous Dosing Schedule in Patients With Various Advanced or Metastatic Non-hematologic Malignancies

The primary objective of this trial is to determine the safety and tolerability of BI 853520 monotherapy by defining the maximum tolerated dose (MTD) and recommending the dose for further trials in the development of this compound.

Secondary objectives are

• determination of the pharmacokinetic (PK) profile;
• exploratory pharmacodynamic analysis; and
• collection of preliminary data on anti-tumour efficacy.

Inclusion criteria:

Inclusion criteria

1. Patients with a confirmed diagnosis of advanced, measurable or evaluable, nonresectable and/or metastatic non-hematologic malignancy, which has shown to be progressive in the last 6 months as demonstrated by serial imaging

2. Patients who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to established treatment options

3. Tumour tissue must be available for the determination of E-cadherin expression (archived tissue or fresh biopsy).

4. Recovery from reversible toxicities (alopecia excluded) of prior anti-cancer therapies (CTCAE grade < 2)

5. Age = 18 years

6. Life expectancy = 3 months

7. Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation, including consent for PK samples, for using an archived tumour sample for determination of Ecadherin status, for reviewing previous tumour scans (and for providing skin biopsies, in patients in dose finding phase enrolled before protocol amendment 03)

8. Eastern Cooperative Oncology Group (ECOG), R01-0787) performance score 0-1

   Additional inclusion criteria in the expansion phase:

9. Patients must have measurable progressive disease within the last 6 months, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1, R09-0262)

10. deleted

11. Patients must be willing to provide paired tumour biopsies for PD determination. Refer to section 5.6.3

12. Patients should fit into one of the categories described below:

I. Metastatic adenocarcinoma of the pancreas Patients should have preferably received at least one line of systemic treatment for metastatic disease and preferably not more than 2 prior regimens for metastatic disease.

II. Platinum-resistant ovarian carcinoma, defined as recurrence within 6 months after completion of prior platinum-based chemotherapy Patients should have received preferably no more than 5 previous lines of systemic treatment for metastatic disease.

III. Oesophageal carcinoma Patients with oesophageal carcinoma of adenocarcinoma- or squamous cell histology who have received preferably not more than 2 previous lines of systemic treatment for metastatic disease.

IV. Soft tissue sarcoma Patients should preferably have received no more than 2 previous lines of systemic treatment for metastatic disease.

Exclusion criteria:

• Serious concomitant non-oncological disease/illness
• Active/symptomatic brain metastases
• Second malignancy
• Pregnancy or breastfeeding
• Women or men who are sexually active and unwilling to use a medically acceptable method of contraception.
• Treatment with cytotoxic anti-cancer-therapies or investigational drugs within four weeks of the first treatment with the study medication