A Phase 1, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- CC-90011
- Conditions
- Lymphoma, Non-Hodgkin
- Sponsor
- Celgene
- Enrollment
- 75
- Locations
- 15
- Primary Endpoint
- Part A - Number of Participants With Dose Limiting Toxicities (DLTs)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
Study CC-90011-ST-001 is an open-label, Phase 1, dose escalation and expansion, First-In-Human (FIH) clinical study of CC-90011 in subjects with advanced unresectable solid tumors (enriched for grade 2 NENs, grade 2 NETs and NECs) and R/R NHL (MZL, including extranodal MZL [EMZL], splenic MZL [SMZL], nodal MZL [NMZL], and histologic transformation of MZL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90011 to estimate the maximum tolerated dose (MTD) of CC-90011. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90011 administered at or below the MTD in 3 selected expansion cohorts of approximately 10-20 evaluable subjects each, in order to further define the RP2D.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Advanced or unresectable solid tumors including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conventional therapy exists
- •Eastern Cooperative Oncology Group Performance Status of 0 to 1
Exclusion Criteria
- •Prior autologous stem cell transplant ≤ 3 months before first dose or those who have not recovered
- •Symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and gastrointestinal tract hemorrhages
- •Impaired cardiac function or clinically significant cardiac diseases
- •Poor bone marrow reserve as assessed by Investigator
- •Refer to protocol defined exclusion criteria for parts C and D. Other protocol-defined inclusion/exclusion criteria apply
Arms & Interventions
CC-90011 and Rifampicin
Intervention: CC-90011
CC-90011 and Rifampicin
Intervention: Rifampicin
CC-90011 and Itraconazole
Intervention: CC-90011
CC-90011 and Itraconazole
Intervention: Itraconazole
Outcomes
Primary Outcomes
Part A - Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (Each cycle is of 28 days)
Dose-limiting toxicities (DLTs) during dose escalation are defined as follows, occurring within the Cycle 1 (28 days) DLT assessment period, unless clearly unrelated to CC-90011: Any Grade 4 non-hematologic toxicity; any non-hematologic toxicity Grade ≥ 3 except Grade 3 diarrhea, nausea, or vomiting of ≤ 3 days duration, Grade 3 rash resolving to Grade ≤ 2 within 7 days without recurrence, and Grade 3 fatigue resolving to Grade ≤ 2 within 7 days without recurrence. Hematological toxicities include febrile neutropenia, Grade 4 neutropenia \> 7 days, Grade 4 thrombocytopenia \> 7 days, or Grade ≥ 3 thrombocytopenia with significant bleeding. Any AE necessitating dose reduction during Cycle 1, or any other toxicity deemed dose-limiting by the safety committee. The MTD is the highest dose at which less than 33% of the population treated with CC-90011 suffer a DLT in the first cycle and at least 6 evaluable participants have been treated at this dose.
Part A - Maximum Tolerated Dose (MTDs)
Time Frame: Cycle 1 (Each cycle is of 28 days)
The MTD is the highest dose at which less than 33% of the population treated with CC-90011 suffer a DLT in the first cycle and at least 6 evaluable participants have been treated at this dose. Dose-limiting toxicities (DLTs) during dose escalation are defined as follows, occurring within the Cycle 1 (28 days) DLT assessment period, unless clearly unrelated to CC-90011: Any Grade 4 non-hematologic toxicity; any non-hematologic toxicity Grade ≥ 3 except Grade 3 diarrhea, nausea, or vomiting of ≤ 3 days duration, Grade 3 rash resolving to Grade ≤ 2 within 7 days without recurrence, and Grade 3 fatigue resolving to Grade ≤ 2 within 7 days without recurrence. Hematological toxicities include febrile neutropenia, Grade 4 neutropenia \> 7 days, Grade 4 thrombocytopenia \> 7 days, or Grade ≥ 3 thrombocytopenia with significant bleeding. Any AE necessitating dose reduction during Cycle 1, or any other toxicity deemed dose-limiting by the safety committee.
Secondary Outcomes
- Part A - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)(From first dose (Day 1) till disease progression or death due to any cause (up to 803 days))
- Part A - Objective Response Rate as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)(From first dose (Day 1) untill disease progression or death due to any cause (up to 803 days))
- Part A - Duration of Response (DoR) Based on Confirmed Responses(From first dose (Day 1) until disease progression or death due to any cause (up to 803 days))
- Part A - Progression-Free Survival (PFS)(From first dose (Day 1) until disease progression or death due to any cause (up to 803 days))
- Part A - Overall Survival (OS)(From first dose (Day 1) until death due to any cause (up to 803 days))
- Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part A - Time to Cmax (Tmax) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part A - Half-life (t1/2) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part A - Apparent Clearance (CL/F) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part A- Volume of Distribution (Vz/F) of CC-90011(Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days))
- Part B - Clinical Benefit Rate (CBR) as Per Confirmed Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)(From first dose (Day 1) until disease progression or death due to any cause (up to 720 days))
- Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)(From first dose (Day 1) till disease progression or death due to any cause (up to 720 days))
- Part B - Duration of Response (DoR)(From first dose (Day 1) until disease progression or death due to any cause (up to 720 days))
- Part B - Progression Free Survival (PFS)(From first dose (Day 1) until disease progression or death due to any cause (up to 720 days))
- Part B - Overall Survival (OS)(From first dose (Day 1) until death due to any cause (up to 720 days))