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

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

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 Overview

• Status: Terminated
• Conditions: Neoplasms; Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Itraconazole; Drug: CC-90011; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21079
    • Local Institution - 101
  • Marseille Cedex 9, France, 13273
    • Local Institution - 102
  • Villejuif Cedex, France, 94805
    • Local Institution - 100
• Italy
  • Bologna, Italy, 40123
    • Local Institution - 200
  • Milano, Italy, 20133
    • Local Institution - 201
  • Milano, Italy, 20141
    • Local Institution - 202
• Japan
  • Kashiwa, Japan, 277-8577
    • Local Institution - 500
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Local Institution - 501
    • Koto-Ku, Tokyo, Japan, 135-8550
      • Local Institution - 502
• Spain
  • Barcelona, Spain, 08035
    • Local Institution - 400
  • Madrid, Spain, 28040
    • Local Institution - 402
  • Madrid, Spain, 28041
    • Local Institution - 404
  • Santander, Spain, 39008
    • Local Institution - 401
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Local Institution - 300
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Local Institution - 301

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CC-90011 and Rifampicin	Drug: CC-90011; Specified dose on specified days; Drug: Rifampicin; Specified dose on specified days
Experimental: CC-90011 and Itraconazole	Drug: Itraconazole; Specified dose on specified days; Drug: CC-90011; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Cycle 1 (Each cycle is of 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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	Blood samples were collected to assess AUCt. Prespecified to be reported for Part A only.	Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
Part A - Time to Cmax (Tmax) of CC-90011	Blood samples were collected to assess Tmax. Prespecified to be reported for Part A only.	Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
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.	Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
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.	Day 1 and Day 22 of Cycle 1 (Each cycle consist of 28 days)
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.	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)	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.	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)	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.	From first dose (Day 1) till disease progression or death due to any cause (up to 720 days)
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.	From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
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.	From first dose (Day 1) until disease progression or death due to any cause (up to 720 days)
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.	From first dose (Day 1) until death due to any cause (up to 720 days)

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Hollebecque A, Salvagni S, Plummer R, Isambert N, Niccoli P, Capdevila J, Curigliano G, Moreno V, Martin-Romano P, Baudin E, Arias M, Mora S, de Alvaro J, Di Martino J, Parra-Palau JL, Sanchez-Perez T, Aronchik I, Filvaroff EH, Lamba M, Nikolova Z, de Bono JS. Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma. Clin Cancer Res. 2021 Jan 15;27(2):438-446. doi: 10.1158/1078-0432.CCR-20-2380. Epub 2020 Oct 12.
• Hollebecque A, Salvagni S, Plummer R, Niccoli P, Capdevila J, Curigliano G, Moreno V, de Braud F, de Villambrosia SG, Martin-Romano P, Baudin E, Arias M, de Alvaro J, Parra-Palau JL, Sanchez-Perez T, Aronchik I, Filvaroff EH, Lamba M, Nikolova Z, de Bono JS. Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies. Cancer. 2022 Sep 1;128(17):3185-3195. doi: 10.1002/cncr.34366. Epub 2022 Jun 23.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): March 25, 2024
• Study Completion (Actual): March 25, 2024

Study Registration Dates

• First Submitted: August 18, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (Estimated): August 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Cytochrome P-450 CYP3A Inhibitors; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Pulrodemstat besilate; Rifampin; Itraconazole
• Other Study ID Numbers: CC-90011-ST-001