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
Overview
- Phase
- Phase 1
- Intervention
- RO6870810
- Conditions
- Solid Tumors, Advanced Solid Tumors
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 52
- Locations
- 4
- Primary Endpoint
- Number of Participants with DLTs
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
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
Arms & Interventions
RO6870810 (Part 1)
Participants will receive escalated doses of RO67870810 SC. RO6870810 will be escalated at a starting dose of 0.03 milligrams per kilogram (mg/kg) to a maximum of 0.85 mg/kg. Treatment will be administered in treatment cycles of either 21 days or 28 days and continued until PD, adverse events which justify treatment withdrawal, non-adherence, non-compliance, investigator decision, lost to follow-up, enrollment in other clinical study, or unacceptable toxicity.
Intervention: RO6870810
RO6870810 (Part 2)
Participants will receive RO6870810 at doses up to the MTD or up to the highest dose tested if the MTD is not defined. Treatment will be administered in treatment cycles of either 21 days or 28 days and continued until PD, adverse events which justify treatment withdrawal, non-adherence, non-compliance, investigator decision, lost to follow-up, enrollment in other clinical study, or unacceptable toxicity.
Intervention: RO6870810
Outcomes
Primary Outcomes
Number of Participants with DLTs
Time Frame: Day 1 up to Day 28 (or Day 21)
MTD of RO6870810
Time Frame: Day 1 up to Day 28 (or Day 21)
Percentage of Participants with Adverse Events
Time Frame: Baseline up to approximately 47 months
Secondary Outcomes
- Area Under the Concentration Versus Time Curve from Time 0 (Pre-dose) to Time 24 Hours (AUC0-24) of RO6870810(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Median Time Taken for the Best Overall Response Based on RECIST v 1.1 as Determined by the Investigator(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Time to Reach Cmax (Tmax) of RO6870810(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Median Time Taken for the First Response Based on RECIST v 1.1 as Determined by the Investigator(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Overall Survival(Screening up to death due to any cause (up to approximately 47 months))
- Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR]) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Progression Free Survival Based on RECIST v 1.1 as Determined by the Investigator(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Maximum Plasma Concentration (Cmax) of RO6870810(Baseline up to 47 months (detailed timeframe is provided in the outcome description))
- Duration of Response Based on RECIST v 1.1 as Determined by the Investigator(Baseline up to 47 months (detailed timeframe is provided in the outcome description))