Lymphoma, Non-Hodgkin, Neoplasms
Conditions
Keywords
Safety, CC-90011, Advanced unresectable solid Tumors, Low intermediate-grade lung neuroendocrine tumors (Typical and Atypical carcinoids), Neuroendocrine prostate cancer (NEPC), R/R Non-Hodgkin's Lymphomas
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.
Interventions
DRUGCC-90011
Specified dose on specified days
DRUGRifampicin
Specified dose on specified days
DRUGItraconazole
Specified dose on specified days
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | Duration of response 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. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part A - Progression-Free Survival (PFS) | From first dose (Day 1) until disease progression or death due to any cause (up to 803 days) | Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part A - Overall Survival (OS) | From first dose (Day 1) until death due to any cause (up to 803 days) | Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology. |
| Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) | Blood samples were collected to assess Cmax. Prespecified to be reported for Part A only. |
| 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) | Blood samples were collected to assess AUCt. Prespecified to be reported for Part A only. |
| Part A - Time to Cmax (Tmax) of CC-90011 | Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) | Blood samples were collected to assess Tmax. Prespecified to be reported for Part A only. |
| Part A - Half-life (t1/2) of CC-90011 | Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) | Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only. |
| 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) | The Clinical benefit rate (CBR) is defined as percentage of participants with tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part A- Volume of Distribution (Vz/F) of CC-90011 | Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) | Blood samples were collected to assess Vz/F. Prespecified to be reported for Part A only. |
| 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) | The Clinical Benefit Rate (CBR) is defined as tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| 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) | The Objective Response Rate (ORR) is defined as the percent of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part B - Duration of Response (DoR) | From first dose (Day 1) until disease progression or death due to any cause (up to 720 days) | Duration of response 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. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part B - Progression Free Survival (PFS) | From first dose (Day 1) until disease progression or death due to any cause (up to 720 days) | Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
| Part B - Overall Survival (OS) | From first dose (Day 1) until death due to any cause (up to 720 days) | Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology. |
| Part A - Apparent Clearance (CL/F) of CC-90011 | Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days) | Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only. |
| 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) | The Objective Response Rate (ORR) is defined as the percentage of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm. |
Countries
France, Italy, Japan, Spain, United Kingdom
Participant flow
Pre-assignment details
Participants were not enrolled in Part C and Part D as the study was terminated early.
Participants by arm
| Arm | Count |
|---|---|
| Part A 1.25 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received CC-90011 capsule orally once per week of different doses. | 4 |
| Part A 2.5 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 2.5 mg of CC-90011 capsule orally once per week. | 5 |
| Part A 5 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 5 mg of CC-90011 capsule orally once per week. | 6 |
| Part A 10 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 10 mg of CC-90011 capsule orally once per week. | 4 |
| Part A 20 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 20 mg of CC-90011 capsule orally once per week. | 5 |
| Part A 40 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 40 mg of CC-90011 capsule orally once per week. | 6 |
| Part A 60 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 60 mg of CC-90011 capsule orally once per week. | 6 |
| Part A 80 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 80 mg of CC-90011 capsule orally once per week. | 10 |
| Part A 120 mg Participants with Advanced Solid Tumors and Non-Hodgkin Lymphomas received 120 mg of CC-90011 capsule orally once per week. | 4 |
| Part B - Lung NETs - 60 mg Participants with advanced low/intermediate-grade Lung Neuroendocrine tumors (NETs) received 60 mg of CC-90011 capsule orally once per week. | 14 |
| Part B - NEPC - 60 mg Participants with neuroendocrine prostate carcinoma (NEPC) received 60 mg of CC-90011 capsule orally once per week. | 2 |
| Part B - MZL - 60 mg Participants with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL) (marginal zone lymphoma \[MZL\], including extranodal marginal zone lymphoma \[EMZL\], splenic marginal zone lymphoma \[SMZL\], nodal marginal zone lymphoma \[NMZL\], and histologic transformation of marginal zone lymphoma (MZL) received 60 mg of CC-90011 capsule orally once per week. | 3 |
| Part B - Japanese Cohort - 60 mg Japanese participants with relapsed and/or refractory (R/R) advanced unresectable solid tumors (including grade 2 neuroendocrine neoplasm \[NENs\]/NETs) and R/R non-Hodgkin lymphoma (NHLs) (including diffuse large B-cell lymphoma \[DLBCL\] and follicular lymphoma \[FL\] or MZL) received 60 mg of CC-90011 capsule orally once per week | 6 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 4 | 3 | 4 | 2 | 3 | 5 | 7 | 3 | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other reasons | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 2 | 3 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A 2.5 mg | Part A 5 mg | Part A 1.25 mg | Part A 10 mg | Part A 20 mg | Part A 40 mg | Part A 60 mg | Part A 80 mg | Part A 120 mg | Part B - Lung NETs - 60 mg | Part B - NEPC - 60 mg | Part B - MZL - 60 mg | Part B - Japanese Cohort - 60 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 7 Participants | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 2 Participants | 3 Participants | 8 Participants | 2 Participants | 7 Participants | 2 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 3 Participants | 7 Participants | 1 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 7 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 7 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 3 Participants | 7 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 34 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 4 Participants | 3 Participants | 7 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 41 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 6 Participants | 1 Participants | 7 Participants | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 4 / 5 | 3 / 6 | 4 / 4 | 2 / 5 | 3 / 6 | 5 / 6 | 7 / 10 | 3 / 4 | 14 / 25 |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 5 / 6 | 3 / 4 | 5 / 5 | 6 / 6 | 6 / 6 | 10 / 10 | 4 / 4 | 25 / 25 |
| serious Total, serious adverse events | 2 / 4 | 2 / 5 | 2 / 6 | 0 / 4 | 0 / 5 | 5 / 6 | 3 / 6 | 6 / 10 | 3 / 4 | 7 / 25 |
Outcome results
Primary
Part A - Maximum Tolerated Dose (MTDs)
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.
Time frame: Cycle 1 (Each cycle is of 28 days)
Population: DLT Evaluable Population includes participants in Part A are evaluable for DLT if they received at least 75% of the total planned dose of CC-90011 during Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 1.25 mg | Part A - Maximum Tolerated Dose (MTDs) | 60 milligram |
Primary
Part A - Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Time frame: Cycle 1 (Each cycle is of 28 days)
Population: DLT Evaluable Population includes participants in Part A are evaluable for DLT if they received at least 75% of the total planned dose of CC-90011 during Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A 1.25 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 2.5 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 5 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 10 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 20 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 40 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A 60 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part A 80 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Part A 120 mg | Part A - Number of Participants With Dose Limiting Toxicities (DLTs) | 4 Participants |
Secondary
Part A - Apparent Clearance (CL/F) of CC-90011
Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A 2.5 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 35.61 Litres per hours | — |
| Part A 5 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 95.70 Litres per hours | Geometric Coefficient of Variation 20.82 |
| Part A 10 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 80.08 Litres per hours | Geometric Coefficient of Variation 44.68 |
| Part A 20 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 64.69 Litres per hours | Geometric Coefficient of Variation 79.21 |
| Part A 40 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 63.23 Litres per hours | Geometric Coefficient of Variation 23.92 |
| Part A 60 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 73.37 Litres per hours | Geometric Coefficient of Variation 65.85 |
| Part A 80 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 81.99 Litres per hours | Geometric Coefficient of Variation 50.36 |
| Part A 120 mg | Part A - Apparent Clearance (CL/F) of CC-90011 | Cycle 1 Day 1 | 57.51 Litres per hours | Geometric Coefficient of Variation 27.62 |
Secondary
Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011
Blood samples were collected to assess AUCt. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A 1.25 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 5.806 h*ng/mL | Geometric Coefficient of Variation 55.98 |
| Part A 1.25 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 11.48 h*ng/mL | Geometric Coefficient of Variation 40.94 |
| Part A 2.5 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 24.47 h*ng/mL | Geometric Coefficient of Variation 76.85 |
| Part A 2.5 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 23.54 h*ng/mL | Geometric Coefficient of Variation 25.12 |
| Part A 5 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 45.30 h*ng/mL | Geometric Coefficient of Variation 46.78 |
| Part A 5 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 44.77 h*ng/mL | Geometric Coefficient of Variation 35.77 |
| Part A 10 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 125.53 h*ng/mL | Geometric Coefficient of Variation 8.738 |
| Part A 10 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 103.07 h*ng/mL | Geometric Coefficient of Variation 42.47 |
| Part A 20 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 237.12 h*ng/mL | Geometric Coefficient of Variation 83.11 |
| Part A 20 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 179.48 h*ng/mL | Geometric Coefficient of Variation 136.69 |
| Part A 40 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 551.55 h*ng/mL | Geometric Coefficient of Variation 19.29 |
| Part A 40 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 337.92 h*ng/mL | Geometric Coefficient of Variation 30.72 |
| Part A 60 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 704.82 h*ng/mL | Geometric Coefficient of Variation 60.95 |
| Part A 60 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 625.53 h*ng/mL | Geometric Coefficient of Variation 24.73 |
| Part A 80 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle Day 22 | 654.76 h*ng/mL | Geometric Coefficient of Variation 55.42 |
| Part A 80 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 849.47 h*ng/mL | Geometric Coefficient of Variation 45.94 |
| Part A 120 mg | Part A - Area Under the Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt) of CC-90011 | Cycle 1 Day 1 | 1736.85 h*ng/mL | Geometric Coefficient of Variation 25.11 |
Secondary
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)
The Clinical benefit rate (CBR) is defined as percentage of participants with tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) till disease progression or death due to any cause (up to 803 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011 and prespecified to be reported for Part A only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 1.25 mg | 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) | 0.0 percentage of participants |
| Part A 2.5 mg | 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) | 0.0 percentage of participants |
| Part A 5 mg | 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) | 16.7 percentage of participants |
| Part A 10 mg | 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) | 0.0 percentage of participants |
| Part A 20 mg | 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) | 20.0 percentage of participants |
| Part A 40 mg | 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) | 50.0 percentage of participants |
| Part A 60 mg | 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) | 33.3 percentage of participants |
| Part A 80 mg | 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) | 30.0 percentage of participants |
| Part A 120 mg | 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) | 0.0 percentage of participants |
Secondary
Part A - Duration of Response (DoR) Based on Confirmed Responses
Duration of response 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. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) until disease progression or death due to any cause (up to 803 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Treated Population with Confirmed Best Response of CR or PR. Prespecified to be reported for Part A only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 80 mg | Part A - Duration of Response (DoR) Based on Confirmed Responses | NA months |
Secondary
Part A - Half-life (t1/2) of CC-90011
Blood samples were collected to assess CL/F. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A 1.25 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 34.33 hour |
| Part A 1.25 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 77.27 hour |
| Part A 2.5 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 73.07 hour |
| Part A 2.5 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 73.25 hour |
| Part A 5 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 53.62 hour |
| Part A 5 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 79.30 hour |
| Part A 10 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 72.52 hour |
| Part A 10 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 70.54 hour |
| Part A 20 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 55.76 hour |
| Part A 20 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 68.35 hour |
| Part A 40 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 59.82 hour |
| Part A 40 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 71.88 hour |
| Part A 60 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 63.88 hour |
| Part A 60 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 61.03 hour |
| Part A 80 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle Day 22 | 56.03 hour |
| Part A 80 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 58.52 hour |
| Part A 120 mg | Part A - Half-life (t1/2) of CC-90011 | Cycle 1 Day 1 | 67.33 hour |
Secondary
Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011
Blood samples were collected to assess Cmax. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis. Prespecified to be reported for Part A only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A 1.25 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 0.4077 ng/mL | Geometric Coefficient of Variation 35.18 |
| Part A 1.25 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 0.4181 ng/mL | Geometric Coefficient of Variation 48.3 |
| Part A 2.5 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 0.8042 ng/mL | Geometric Coefficient of Variation 46.38 |
| Part A 2.5 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 0.7708 ng/mL | Geometric Coefficient of Variation 42.21 |
| Part A 5 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 1.651 ng/mL | Geometric Coefficient of Variation 45.37 |
| Part A 5 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 1.520 ng/mL | Geometric Coefficient of Variation 39.99 |
| Part A 10 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 3.886 ng/mL | Geometric Coefficient of Variation 28.94 |
| Part A 10 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 2.514 ng/mL | Geometric Coefficient of Variation 32.41 |
| Part A 20 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 6.924 ng/mL | Geometric Coefficient of Variation 62.53 |
| Part A 20 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 4.526 ng/mL | Geometric Coefficient of Variation 75.8 |
| Part A 40 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 16.28 ng/mL | Geometric Coefficient of Variation 40.03 |
| Part A 40 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 10.85 ng/mL | Geometric Coefficient of Variation 29.33 |
| Part A 60 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 23.02 ng/mL | Geometric Coefficient of Variation 55.31 |
| Part A 60 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 20.43 ng/mL | Geometric Coefficient of Variation 51.67 |
| Part A 80 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle Day 22 | 25.26 ng/mL | Geometric Coefficient of Variation 62.11 |
| Part A 80 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 23.66 ng/mL | Geometric Coefficient of Variation 37.6 |
| Part A 120 mg | Part A - Maximum Observed Plasma Concentration (Cmax) of CC-90011 | Cycle 1 Day 1 | 42.03 ng/mL | Geometric Coefficient of Variation 45.99 |
Secondary
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)
The Objective Response Rate (ORR) is defined as the percentage of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) untill disease progression or death due to any cause (up to 803 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011 and prespecified to be reported for Part A only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 1.25 mg | 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) | 0.0 percentage of participants |
| Part A 2.5 mg | 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) | 0.0 percentage of participants |
| Part A 5 mg | 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) | 0.0 percentage of participants |
| Part A 10 mg | 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) | 0.0 percentage of participants |
| Part A 20 mg | 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) | 0.0 percentage of participants |
| Part A 40 mg | 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) | 0.0 percentage of participants |
| Part A 60 mg | 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) | 0.0 percentage of participants |
| Part A 80 mg | 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) | 10.0 percentage of participants |
| Part A 120 mg | 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) | 0.0 percentage of participants |
Secondary
Part A - Overall Survival (OS)
Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology.
Time frame: From first dose (Day 1) until death due to any cause (up to 803 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part A only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 1.25 mg | Part A - Overall Survival (OS) | 315.0 days |
| Part A 2.5 mg | Part A - Overall Survival (OS) | 189.0 days |
| Part A 5 mg | Part A - Overall Survival (OS) | 611.0 days |
| Part A 10 mg | Part A - Overall Survival (OS) | 322.5 days |
| Part A 20 mg | Part A - Overall Survival (OS) | NA days |
| Part A 40 mg | Part A - Overall Survival (OS) | NA days |
| Part A 60 mg | Part A - Overall Survival (OS) | NA days |
| Part A 80 mg | Part A - Overall Survival (OS) | 139.0 days |
| Part A 120 mg | Part A - Overall Survival (OS) | 238.0 days |
Secondary
Part A - Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) until disease progression or death due to any cause (up to 803 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part A only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 1.25 mg | Part A - Progression-Free Survival (PFS) | 96.0 days |
| Part A 2.5 mg | Part A - Progression-Free Survival (PFS) | 53.0 days |
| Part A 5 mg | Part A - Progression-Free Survival (PFS) | 107.0 days |
| Part A 10 mg | Part A - Progression-Free Survival (PFS) | 51.5 days |
| Part A 20 mg | Part A - Progression-Free Survival (PFS) | 588.0 days |
| Part A 40 mg | Part A - Progression-Free Survival (PFS) | 162.0 days |
| Part A 60 mg | Part A - Progression-Free Survival (PFS) | 111.5 days |
| Part A 80 mg | Part A - Progression-Free Survival (PFS) | 52.0 days |
| Part A 120 mg | Part A - Progression-Free Survival (PFS) | 107.0 days |
Secondary
Part A - Time to Cmax (Tmax) of CC-90011
Blood samples were collected to assess Tmax. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A 1.25 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 2.083 hours |
| Part A 1.25 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 2.008 hours |
| Part A 2.5 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 2.017 hours |
| Part A 2.5 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 2.992 hours |
| Part A 5 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 3.917 hours |
| Part A 5 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 4.042 hours |
| Part A 10 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 4.000 hours |
| Part A 10 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 2.000 hours |
| Part A 20 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 4.567 hours |
| Part A 20 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 4.183 hours |
| Part A 40 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 4.117 hours |
| Part A 40 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 4.067 hours |
| Part A 60 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 4.075 hours |
| Part A 60 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 3.950 hours |
| Part A 80 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle Day 22 | 2.083 hours |
| Part A 80 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 4.042 hours |
| Part A 120 mg | Part A - Time to Cmax (Tmax) of CC-90011 | Cycle 1 Day 1 | 3.242 hours |
Secondary
Part A- Volume of Distribution (Vz/F) of CC-90011
Blood samples were collected to assess Vz/F. Prespecified to be reported for Part A only.
Time frame: Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Population: The PK Evaluable Population included all participants who enrolled, received at least 1 dose of CC-90011, and had at least 1 measurable concentration of CC-90011. Only participants with data available at the specified timepoints are included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A 2.5 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 3400.66 Litre | — |
| Part A 5 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 7814.20 Litre | Geometric Coefficient of Variation 50.12 |
| Part A 10 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 8076.70 Litre | Geometric Coefficient of Variation 44.02 |
| Part A 20 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 5734.70 Litre | Geometric Coefficient of Variation 64 |
| Part A 40 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 5506.05 Litre | Geometric Coefficient of Variation 20.02 |
| Part A 60 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 7245.99 Litre | Geometric Coefficient of Variation 73.93 |
| Part A 80 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 6984.46 Litre | Geometric Coefficient of Variation 37.88 |
| Part A 120 mg | Part A- Volume of Distribution (Vz/F) of CC-90011 | Cycle 1 Day 1 | 5598.55 Litre | Geometric Coefficient of Variation 19.95 |
Secondary
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)
The Clinical Benefit Rate (CBR) is defined as tumor responses (as assessed by the Investigators) of CR, PR and durable SD (SD of ≥ 4 months duration). Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part B only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 1.25 mg | 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) | 50.0 percentage of participants |
| Part A 2.5 mg | 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) | 0.0 percentage of participants |
| Part A 5 mg | 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) | 0.0 percentage of participants |
| Part A 10 mg | 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) | 16.7 percentage of participants |
Secondary
Part B - Duration of Response (DoR)
Duration of response 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. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Treated Population with Confirmed Best Response of CR or PR. Prespecified to be reported for Part B only.
Secondary
Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1)
The Objective Response Rate (ORR) is defined as the percent of participants whose best response is CR or PR. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as \\\>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) till disease progression or death due to any cause (up to 720 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part B only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A 1.25 mg | Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) | 0.0 percentage of participants |
| Part A 2.5 mg | Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) | 0.0 percentage of participants |
| Part A 5 mg | Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) | 0.0 percentage of participants |
| Part A 10 mg | Part B - Objective Response Rate as Per Confirmed Best Overall Response Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (RECIST 1.1) | 0.0 percentage of participants |
Secondary
Part B - Overall Survival (OS)
Overall Survival (OS) is defined as the time from the first dose of study drug to death due to any cause based on Kaplan-Meier methodology.
Time frame: From first dose (Day 1) until death due to any cause (up to 720 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part B only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 1.25 mg | Part B - Overall Survival (OS) | 720.0 days |
| Part A 2.5 mg | Part B - Overall Survival (OS) | 307.0 days |
| Part A 5 mg | Part B - Overall Survival (OS) | NA days |
| Part A 10 mg | Part B - Overall Survival (OS) | 180.0 days |
Secondary
Part B - Progression Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause based on Kaplan-Meier methodology Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.
Time frame: From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
Population: The Treated Population included all participants who enrolled and received at least 1 dose of CC-90011. Prespecified to be reported for Part B only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A 1.25 mg | Part B - Progression Free Survival (PFS) | 140.5 days |
| Part A 2.5 mg | Part B - Progression Free Survival (PFS) | 38.0 days |
| Part A 5 mg | Part B - Progression Free Survival (PFS) | 28.0 days |
| Part A 10 mg | Part B - Progression Free Survival (PFS) | 81.5 days |