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

NCT01987362

CompletedPhase 1

Sponsor: Hoffmann-La Roche

Conditions: Solid Tumors, Advanced Solid Tumors

Interventions: RO6870810

Countries: United States

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.

Eligibility overview

Sex: ALL

Age: 18 Years to

Healthy volunteers: Yes

Study type: INTERVENTIONAL

Eligibility criteria
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
Locations (4)
  • New Haven, Connecticut, United States
  • Boston, Massachusetts, United States
  • Detroit, Michigan, United States
  • Cleveland, Ohio, United States