Study CC-90010-ST-001 is an open-label, Phase 1a, dose escalation and expansion, First-in-human (FIH) clinical study of CC-90010 in subjects with advanced or unresectable solid tumors and relapsed and/or refractory advanced Non-Hodgkin's lymphoma (NHL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90010 to estimate the maximum tolerated dose (MTD) of CC-90010. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90010 administered at or below the MTD in the following cohorts: Cohort 1: relapsed and/or refractory DLBCL approximately 20-25 evaluable subjects at 45 mg CC-90010 4-days-on/24-days-off in each 28-day cycle Cohort 2: advanced BCC -enrollment stopped due to recruitment challenges Cohort 3: relapsed and/or refractory DLBCL -approximately 15 evaluable subjects at 30mg CC-90010 3-dayson/11-days-offin each 28-day cycle. The enrollment of subjects with R/R DLBCL in Cohort 1 and Cohort 3 was closed due to Company's strategic decision and not due to any safety concern or lack of preliminary antitumor efficacy. The food effect assessment (Part C, Spain only) will evaluate the impact of food on CC-90010 when administered at the RP2D of 45 mg 4-days-on/24-days-off (180 mg per 28-day cycle), by comparison of the PK parameters following fasted and fed (high-fat, high-calorie meal) conditions.
Parts A, B and C will consist of 3 periods: Screening, Treatment and Follow-up. Screening Period: The Screening Period starts 28 days (± 3 days) prior to first dose of CC-90010. The informed document (ICD) must be signed and dated by the subject and the administering staff prior to the start of any other study procedures. All screening tests and procedures must be completed within the 28 days (±3 days) prior to the first dose of CC-90010. Treatment Period: During the Treatment Period, CC-90010 was initially administered orally once daily for 3 consecutive days followed by 4 consecutive days off drug every week (3/7-days schedule) in each 28-day cycle in Part A. Alternative dosing schedules (eg, 2-days-on/5-days- off each week, 3-days-on/4-days-off every other week, 4-days on/24 days off) may be evaluated one dosing schedule at a time or ≥ 2 dosing schedules given in parallel, based on the review of available safety, PK, pharmacodynamic (PD), and efficacy data by the SRC. Following completion of dose escalation in Part A, selected expansion cohorts will receive CC-90010 in Part B. The SRC determined the RP2D for Part B to be 45 mg CC-90010 given once daily for 4 consecutive days on followed by 24 consecutive days off (4-days-on/24-days-off) in each 28-day cycle. There are 3 cohorts in Part B expansion. A cohort of up to approximately 20-25 subjects with relapsed and/or refractory DLBCL (Cohort 1) enrolled at the RP2D.. Enrollment in advanced BCC (Cohort 2) will be stopped due to recruitment challenges. An additional cohort of approximately 15 evaluable subjects with R/R DLBCL (Cohort 3) will be enrolled under an alternative dosing regimen of 30 mg CC-90010 3days-on/11-days off in each 28-day cycle. The enrollment of subjects with R/R DLBCL in Cohort 1 and Cohort 3 was closed due to Company's strategic decision and not due to any safety concern or lack of preliminary antitumor efficacy. The food effect assessment (Part C, Spain only) will evaluate the impact of food on CC-90010 when administered at the RP2D of 45 mg 4-days-on/24-days-off, by comparison of PK parameters following fasted and fed (high-fat, high-calorie meal) conditions in approximately 24 subjects with advanced solid tumors. Follow-up Period: In the Follow-up Period, subjects will be followed for 28 days (± 3 days) after the last dose of CC-90010 for safety. After the Safety Follow-up visit, all subjects will be followed every subsequent 3 months (± 2 weeks) for survival follow-up for up until 2 years or until death, lost to follow-up, or the End of Trial, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
139
CC-90010 is an oral, potent and reversible inhibitor of the epigenetic target bromodomain and extra-terminal (BET) proteins.
Local Institution - 102
Bordeaux, France
Local Institution - 100
Villejuif, France
Local Institution - 303
Meldola, Italy
Local Institution - 301
Napoli, Campania, Italy
Local Institution - 302
Rozzano (MI), Italy
Local Institution - 400
Kashiwa-shi, Chiba, Japan
Local Institution - 402
Koto-ku, Tokyo, Japan
Local Institution - 401
Chikusa-ku, Japan
Local Institution - 200
Barcelona, Spain
Local Institution - 201
Madrid, Spain
...and 1 more locations
Adverse Events (AEs)
Number of participants with adverse events
Time frame: Up to 7 years
Dose Limiting Toxicities (DLTs)
A DLT is defined as any of the toxicities described in the protocol occurring within the DLT assessment unless the event can clearly be determined to be unrelated to CC-90010
Time frame: Up to 7 years
Maximum tolerated dose (MTD)
The MTD is the highest dose that causes DLTs in not more than 33% of the subjects treated with CC-90010 in the first cycle with at least 6 evaluable subjects treated at this dose.
Time frame: Up to 7 years
Clinical benefit rate (CBR)
Is defined as tumor responses (as assessed by the Investigators) of complete response (CR), partial response (PR) and stable disease (SD) (SD of ≥ 4 months duration).
Time frame: Up to 7 years
Objective response rate (ORR)
Is defined as the percent of subjects whose best response is CR or PR.
Time frame: Up to 7 years
Duration of Response Rate
Is measured from the time when criteria for CR/PR are first met (whichever is first recorded) until the first date at which progressive disease is objectively documented
Time frame: Up to 7 years
Duration of stable disease
For subjects with best response of SD, duration of SD is measured from the first dose date until the criteria for progression are met
Time frame: Up to 7 years
Progression-free survival (PFS)
Is defined as the time from the first dose of CC-90010 to the first occurrence of disease progression or death from any cause.
Time frame: Up to 7 years
Overall survival
Is measured as the time from the first dose of CC-90010 to death due to any cause.
Time frame: Up to 7 years
Pharmacokinetic- Cmax
Maximum observed plasma concentration on first and last day of dosing within a cycle
Time frame: Up to 7 years
Pharmacokinetic- AUC
Area under the plasma concentration time-curve on first and last day of dosing within a cycle
Time frame: Up to 7 years
Pharmacokinetic- Tmax
Time to maximum plasma concentration on first and last day of dosing within a cycle
Time frame: Up to 7 years
Pharmacokinetic- t1/2
Terminal half-life on last day of dosing within a cycle
Time frame: Up to 7 years
Apparent Clearance
Apparent total systemic clearance to be estimated following the last dose in cycle 1
Time frame: Up to 7 years
Apparent Volume of Distribution
Apparent steady state volume of distribution to be estimated following the last dose in cycle 1
Time frame: Up to 7 years
Pharmacokinetic- AUClast
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Time frame: Up to 7 years
Pharmacokinetic- AUC0-24
Area under the plasma concentration-time curve calculated from time zero to 24 hours
Time frame: Up to 7 years
Pharmacokinetic- AUC0-∞
Area under the concentration-time curve calculated from time zero to infinity
Time frame: Up to 7 years
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