A Two Part Study of RO6870810. Dose-Escalation Study in Participants With Advanced Solid Tumors and Expansion Study in Participants With Selected Malignancies

Status:	Completed
Conditions:	Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	1/7/2018
Start Date:	October 16, 2013
End Date:	October 11, 2017

A Two-Part, Phase I, Multicenter, Open-Label Study of RO6870810/TEN-010 Given Subcutaneously: Part A: A Dose-Escalation Study in Patients With Advanced Solid Tumors. Part B: An Expansion Cohort in Patients With Selected Malignancies

This is a Phase 1, non-randomized, dose-escalating, open label, multi-center study to be
conducted in two parts (Part A and Part B). RO6870810 is a small molecule, non-covalent
inhibitor of bromodomain and extra-terminal (BET) family of bromodomains. This study is
designed to characterize the safety, tolerability, pharmacokinetics and anti-tumor activity
of RO6870810 in participants with histologically confirmed solid tumors with progressive
disease (PD) which is refractory or intolerant to standard/approved therapies. In Part A,
RO6870810 will be administered by subcutaneous (SC) injection daily for either 21 consecutive
days in a 28-day cycle or for 14 consecutive days in a 21-day treatment cycle in participants
with advanced solid tumor malignancies to determine the maximum tolerated dose (MTD) and
dose-limiting toxicities (DLT). In Part B, RO6870810 will be administered at a dose up to the
MTD to further characterize the safety profile and biological effect in a subset of
participants with advanced solid tumor malignancies. It is anticipated that a total of 84
participants will be enrolled in to this study (54 in Part A and 30 in Part B). In addition,
it is expected that up to 20 participants with histologically confirmed nuclear protein in
testis (NUT)-midline carcinoma (NMC) with progressive disease requiring therapy will be
enrolled in the sub-study of Parts A and B. In addition, up to 20 participants with diffuse
large B-cell lymphoma (DLBCL) may be enrolled at selected study sites.

Inclusion Criteria:

General:

- Participants with solid tumors must have one or more metastatic tumors evaluable or
measurable on radiographic imaging

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (or 2 upon
approval by the medical monitor)

- Life expectancy of greater than or equal to (>/=) 3 months

- Disease-free of active second/secondary or prior malignancies >/= 2 years with the
exception of currently treated basal cell, squamous cell carcinoma of the skin, or
carcinoma "in-situ" of the cervix or breast

- Adequate hematological, renal, hepatic and coagulation laboratory test results

- Women of child bearing potential and men must agree to use adequate contraception
during the study and for 4 months after the last dose of study drug

Advanced Solid Malignancies:

- Participants with previously treated, histologically confirmed advanced solid
malignancy with progressive disease requiring therapy

- Participants must be refractory or intolerant to standard therapy

NUT-midline carcinoma:

- Participants with histologically confirmed newly diagnosed or relapsed/refractory NMC
with PD requiring therapy

- Diagnosis of one of the following is required:

1. NUT Midline Carcinoma based on ectopic expression of NUT protein as determined by
Immunohistochemistry (IHC) and/or;

2. Detection of NUT gene translocation as determined by Fluorescence In-Situ
Hybridization (FISH) Advanced Aggressive DLBCL

- Histologically confirmed advanced aggressive B-cell lymphoma with abnormal MYC
expression with persistent disease requiring treatment

- Participants must have relapsed or progressed after at least 2 lines of prior therapy
and not eligible for any curative treatment

- Participants must have measurable disease

Exclusion Criteria:

- Participants with hematologic malignancies

- New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia

- Have Fridericia-corrected QT interval (QTcF) greater than (>) 470 milliseconds (msec)
(female) or > 450 (male), or history of congenital long QT syndrome

- Active, uncontrolled bacterial, viral, or fungal infections

- Known clinically important respiratory impairment

- Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen, or
hepatitis C antibodies

- History of major organ transplant

- History of an autologous or allogeneic bone marrow transplant. For DLBCL participants
only: DLBCL participants may have had a previous autologous transplant but not within
90 days of study entry

- Symptomatic central nervous system malignancy or metastasis

- Pregnant or nursing

- Treatment with surgery or chemotherapy within 28 days prior to study entry

- Prior treatment with small molecule (BET) family inhibitor

- Radiation for symptomatic lesions within 14 days of study enrollment

We found this trial at

sites

Karmanos Cancer Center

Detroit, Michigan 48202

from

Detroit, MI