a two part study of ro6870810. dose-escalation study in participants with advanced solid tumors and expansion study in participants with selected malignancies

Conditions: Solid Tumors, Advanced Solid Tumors

Summary: 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 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