A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas

Phase 1TerminatedNCT02875223

Celgene75 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphoma, Non-Hodgkin Neoplasms

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (15)

Local Institution - 101

Dijon, France

Local Institution - 102

Marseille, France

Local Institution - 100

Villejuif, France

Local Institution - 200

Bologna, Italy

Local Institution - 201

Milan, Italy

Local Institution - 202

Milan, Italy

Local Institution - 501

Chuo-ku, Tokyo, Japan

Local Institution - 502

Koto-Ku, Tokyo, Japan

Local Institution - 500

Kashiwa, Japan

Local Institution - 400

Barcelona, Spain

...and 5 more locations

Outcomes

Primary Outcomes

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)

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)

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)

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)

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)

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)

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)

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)

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.