Open-Label Multicenter 2-Arm Phase I Study of RO5429083 with Dose-Escalation and Extension Cohorts, and Imaging Cohorts with RO5429083 and 89Zr-labeled RO5429083, in Patients with Metastatic and/or Locally Advanced, CD44-Expressing, Malignant Solid Tumors

Cancer remains a major cause of mortality and morbidity worldwide despite
recent progress with drugs providing survival benefit to patients. For most
solid tumors and for many hematologic malignancies, the risk for the
development of metastases and the rate of tumor recurrence are substantial.
Therefore, the medical need for new, effective, and safe treatments of
malignant diseases remains high.
It is widely reported that hyaluronan-CD44 interactions are important in both
malignancy and resistance to therapy. Prevalence data with human tumor samples
further supports the clinical evaluation in various solid tumors and
hematological malignancies

Arm A-Dose Escalation Cohort
Primary Objectives
* To describe the pharmacokinetics (PK) and safety profiles (including the
maximum tolerated dose (MTD) or Optimal Biological Dose) of escalating doses
of RO5429083 in patients with metastatic and/or locally advanced malignant
CD44-expressing solid tumors.


Arm A-Extension Cohort
Primary Objectives
• To investigate the Tumor Growth Control Rate (TGCR): complete response (CR),
partial response (PR), and stable disease (SD).
• To describe the safety profile of RO5429083 in patients with metastatic
and/or locally advanced malignant CD44-expressing solid tumors.
• To determine the recommended Phase II dose.


Arm B: Imaging Study with 89Zr labeled RO5429083
Primary Objectives
• To evaluate the in vivo biodistribution and organ pharmacokinetics of 89Zr
labeled RO5429083 in patients with CD44-expressing solid tumors.

This is a first in human, open-label, multicenter, Phase I clinical study of
RO5429083 and 89Zr labeled RO5429083. The study will be conducted with two
arms. Arm A will be a dose-escalation schedule with an extension cohort which
will seek to evaluate the PK, safety, recommended Phase II dose, and efficacy
of RO5429083 in patients with metastatic and/or locally advanced malignant
CD44-expressing solid tumors. Arm B will be performed at VUmc in the
Netherlands. Arm B will explore body distribution and kinetics using PET with
89 Zr labeled RO5429083 in CD44-expressing patients with advanced squamous cell
carcinoma of the head and neck as well as squamous cell carcinoma of the
esophagus with an option to add other indications if needed.

Arm A will be a multi-center standard *3+3* design and will consist of cohorts
of a minimum of 3 patients which will be sequentially enrolled in one of the
dose levels of RO5429083 administered intravenous on a q2W (defined as 1 dose
of RO5429083 followed by 13 days without treatment every 2 weeks; 1 cycle = 2
weeks) schedule. Dose-escalation will be based on the safety evaluation of
patients after two cycles (q2W x 2) at each dose level

Arm B: 89Zr-labeled RO5429083 will be administered intravenously.

There is the risk of slight pain, bruising or infection when your blood is
drawn. Drawing blood may cause some people to faint.
Having a CT, MRI or PET scan may mean some added discomfort to you. In
particular, you may be bothered by feelings of claustrophobia and the noise
during the test.
The glue used to keep the electrodes in place during the ECG may irritate your
skin and cause redness.

This is the first research study to use RO5429083 in patients currently. No new
information about possible side effects of RO5429083 in patients has been found
other than already formulated upfront the study (based on similar antibody
products).