NeoplasmsPhase 2NCT04350463
A Safety and Efficacy Study of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers
A Phase 2 study testing CC-90011 and Nivolumab in people with Neoplasms, run by Celgene at 37 sites in 6 countries.
Trial summary
This is a Phase 2, multicenter, open-label, multi-cohort study to assess safety and efficacy of CC-90011 in combination with nivolumab in subjects with small cell lung cancer or squamous non-small cell lung cancer who have progressed after 1 or 2 lines of therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- CC-90011 and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 37 sitesin 6 countries
- Study dates
- 14 Jul 2020to 19 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Subject with histological or cytological confirmation of extensive stage Small Cell Lung Cancer (ES SCLC) or Stage IIIb or IV squamous Non-Small Cell Lung Cancer (sqNSCLC)
- Subject has received 1 or 2 prior lines of therapies, defined as:
- Cohort A (SCLC, Immune Checkpoint Inhibitor naïve):
- At least 1 prior treatment including a platinum-based chemotherapy doublet
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- A minimum of 3 cycles of platinum-based chemotherapy in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity
- Cohort B (SCLC, ICI progressors):
- At least 1 prior first or second line treatment includes an ICI
- If treatment includes an ICI as maintenance therapy, at least 1 cycle of ICI in maintenance should have been completed
- At least 1 prior treatment including a platinum-based chemotherapy doublet
- A minimum of 3 cycles of platinum-based chemotherapy, with or without ICI, in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity
- Subject must have progressed during ICI therapy, defined as unequivocal progression on or within 3 months of the last dose of ICI therapy (if no subsequent therapy)
- Cohort C (sqNSCLC, ICI progressors):
- At least 1 prior first or second line treatment includes an ICI
- If treatment includes an ICI as maintenance therapy, at least 1 cycle of ICI in maintenance should have been completed
- At least 1 prior treatment including a platinum-based chemotherapy doublet
- A minimum of 3 cycles of platinum-based chemotherapy, with or without an ICI, in first line treatment, unless stopped at 2 cycles due to treatment-related toxicity
- Subject must have progressed during ICI therapy, defined as unequivocal progression on or within 3 months of the last dose of ICI therapy (if no subsequent therapy)
- Subject has progressed at the last line of therapy.
- Subject has a measurable disease defined by RECIST v1.1.
- Subject agrees to provide a tumor biopsy from primary or metastatic site prior to first dose and at a pre-specified timepoint during treatment. Core biopsy is required however, in the event a core biopsy may not otherwise be feasible in the opinion of the treating physician, an endobronchial ultrasound-guided fine needle aspirate [EBUS-FNA]) biopsy, using the largest gauge needle, may be performed instead.
- Subject has ECOG Performance Status of 0 to 1.
- Subject must have the following laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL (one-time blood transfusion is allowed)
- Platelet (Plt) Count ≥ 150 x 109/L
- White blood cells (WBC) ≥ 2 x 109L
- Serum AST/serum glutamic oxaloacetic transaminase (SGOT) or ALT/serum glutamic pyruvic transaminase (SGPT) ≤ 3 x upper limit of normal (ULN) or ≤ 5 x ULN if presence of liver metastases
- Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN, if Gilbert's syndrome or if indirect bilirubin concentrations are suggestive of extrahepatic source of the elevation)
- Creatinine clearance (CrCl) ≥ 60 mL/minute based on Cockcroft-Gault or modification of diet in renal disease (MDRD) or ≥ 60 mL/min/1.73 m2
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Subject has not recovered to Grade 2 or lower clinically significant toxicities related to the prior therapy (alopecia excluded).
- Subject has received prior LSD1 therapies.
- Subject has a history of severe hypersensitivity reactions to other monoclonal antibodies
- Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
- Subject has recently been treated with whole brain radiation or stereotactic radiosurgery for CNS metastases must have completed therapy at least 2 weeks prior to Cycle 1 Day 1 and has a follow-up brain computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating either stable or improving metastases 2 or more weeks after completion of radiotherapy.
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- Subject must be asymptomatic and off steroids or on stable dose of steroids for at least 2 weeks (≤ 10 mg daily prednisone or equivalent) prior to first dose.
- Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of the study treatments.
- Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
- Subject with any hemorrhage/bleeding event > NCI CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose.
- Subject has any of the following cardiovascular criteria:
- Evidence of acute or ongoing cardiac ischemia
- Current symptomatic pulmonary embolism
- Unstable angina pectoris or myocardial infarction ≤ 6 months prior to enrollment
- Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to enrollment
- Persistent or clinically meaningful ventricular arrhythmias prior to enrollment
- Cerebral vascular accident or transient ischemic attack ≤ 6 months prior to enrollment
- QT corrected based on Fridericia's equation (QTcF) ≥ 450 milliseconds (msec) on Screening ECG, a baseline prolongation of QTcF interval ≥ 450 msec (NCI CTCAE Grade ≥ 2)
- A history of additional risk factors for Torsades de pointes (TdP) (eg, heart failure, hypokalemia, family history of Long QT Syndrome)
- Uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg)
- Subject has known human immunodeficiency virus (HIV) infection.
- Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.
- Subject who is seropositive due to HBV vaccination is eligible.
- Subject who has no active viral infection and is under adequate prophylaxis against HBV reactivation is eligible.
- Subject has any other malignancy within 2 years prior to enrollment, with the exception of adequately treated in-situ bladder cancer, in-situ carcinoma of the cervix, uteri, nonmelanomatous skin cancer, ductal in situ breast carcinoma, thyroid cancer, or early stage prostate cancer (all treatment of which should have been completed 6 months prior to enrollment).
- Subject has medical conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment.
- A brief (≤ 7 days) course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
- Adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease.
- Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted.
- Subject has active autoimmune diseases or history of autoimmune diseases that may relapse. Subjects with the following diseases are allowed to be enrolled after further screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia), or diseases not expected to recur in the absence of external triggering factors.
- Subject is pregnant or nursing.
- Subject has a history of persistent skin rash ≥ NCI CTCAE Grade 2 related to prior ICI therapy.
- Subject has organ transplant history, including allogeneic stem cell transplant.
- Subject has interstitial lung disease history.
- Subject has received a live/attenuated vaccine within 30 days of first dose.
- Subject has previous SARS-CoV-2 infection either suspected or confirmed within 4 weeks prior to screening.
- Acute symptoms must have resolved and based on Investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the subject at a higher risk of receiving investigational treatment.
Trial locations and contacts
37 sites in 6 countries.
37 sites in 6 countries
Spain12 sites
Local Institution - 361
A Coruña, 15006
Local Institution - 351
Badalona (Barcelona), 08916
Local Institution - 355
Barcelona, 08023
Local Institution - 356
Barcelona, 08035
Local Institution - 359
Las Palmas de Gran Canaria, 35016
Local Institution - 358
Madrid, 28027
Local Institution - 353
Madrid, 28040
Local Institution - 357
Madrid, 28041
Local Institution - 360
Majadahonda, Madrid, 28222
Local Institution - 352
Pamplona, 31008
Local Institution - 362
Valencia, 46014
Local Institution - 354
Valencia, 46026
United States8 sites
Local Institution - 105
Canton, Ohio, 44718
Local Institution - 104
Cleveland, Ohio, 44106
Local Institution - 111
Fairfax, Virginia, 22031
Local Institution - 107
Fort Sam Houston, Texas, 78235-8200
Local Institution - 110
Houston, Texas, 77090
Local Institution - 102
Indianapolis, Indiana, 46260
Local Institution - 106
New York, New York, 10021
Local Institution - 109
Pittsburgh, Pennsylvania, 15232
France5 sites
Local Institution - 156
Lyon, 69500
Local Institution - 153
Marseille, 13385
Local Institution - 154
Rennes, 35033
Local Institution - 151
Saint-Herblain, 44800
Local Institution - 152
Villejuif, 94805
Italy5 sites
Local Institution - 301
Aviano, 33081
Local Institution - 306
Meldola, 47014
Local Institution - 303
Milan, 20133
Local Institution - 305
Roma, 00128
Local Institution - 304
Verona, 37134
Poland4 sites
Local Institution - 451
Lodz, 90-242
Local Institution - 452
Lodz, 93-338
Local Institution - 454
Poznan, 60-693
Local Institution - 453
Warsaw, 02-781
United Kingdom3 sites
Local Institution - 254
London, SW3 6JJ
Local Institution - 251
Manchester, M20 4BX
Local Institution - 255
Sutton-Surrey, SM2 5PT
About this study
Official title: A Phase 2, Multicenter, Open-label, Multi-cohort Study to Assess Safety and Efficacy of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers
This is a Phase 2, multicenter, open-label, multi-cohort study to assess safety and efficacy of CC-90011 in combination with nivolumab in subjects with small cell lung cancer or squamous non-small cell lung cancer who have progressed after 1 or 2 lines of therapies.
The primary objectives of the study are to evaluate the overall response rate of subjects treated with CC-90011 in combination with nivolumab in three cohorts:
Read more
- Cohort A: SCLC in ICI naïve subjects
- Cohort B: SCLC in ICI progressor subjects
- Cohort C: sqNSCLC in ICI progressor subjects Overall response rate is defined as the proportion of subjects in the treated population who had complete response (CR) or partial response (PR) as assessed by Investigator review per RECIST v1.1.
In Cohort A, expected ORR for nivolumab monotherapy is 14% while target ORR is 30%. To achieve at least 80% power with one-sided type 1 error 0.1, 39 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 12 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 2 or more subjects responding, Cohort A will continue to enroll an additional 27 subjects. If 1 or less subjects respond in stage 1, Cohort A will stop for futility.
In Cohort B and C, expected ORR for nivolumab monotherapy is 5% while target ORR is 15%. To achieve at least 80% power with one-sided type 1 error 0.1, 48 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 14 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 1 or more subjects responding, Cohort B and C will continue to enroll an additional 34 subjects each. If 0 subjects respond in stage 1, Cohort B and C will stop for futility.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-90011Drug
CC-90011
NivolumabDrug
Nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Arm A: SCLC in ICI naïve subjects | Experimental | CC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle.
Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. Receives: Drug: CC-90011; Drug: Nivolumab |
| Cohort B: SCLC in ICI progressor subjects | Experimental | CC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle.
Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. Receives: Drug: CC-90011; Drug: Nivolumab |
| Cohort C: sqNSCLC in ICI progressor subjects | Experimental | CC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle.
Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. Receives: Drug: CC-90011; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall response rate was defined as the percentage of participants in the treated population who had confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator review per RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression (PD) is defined as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the diameters of new measurable lesions compared to the time of the initial PD.
Measured: Every 6 weeks post Cycle 1 (each cycle is of 28 days) Day 1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participants (up to approximately 33 months)
Secondary outcomes (16)
Number of Participants With Treatment Emergent Adverse Events by Maximal National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Treatment-emergent Adverse Events are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of nivolumab study treatment. AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 1=mild, Grade 2=Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Death).
Measured: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Laboratory Results With CTCAE Toxicity Grade >=3 for Hematology Parameters
Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 =Severe, Grade 4 = Life-threatening).
Measured: Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 18 (each cycle is of 28 days)
Number of Participants With Laboratory Results With CTCAE Toxicity Grade >=3 for Chemistry Parameters
Laboratory results were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 =Severe, Grade 4 = Life-threatening).
Measured: Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 18 (Each cycle is of 28 days)
Number of Participants Receiving Concomitant Medication
Concomitant medication is defined as medications that were either initiated before the first dose of study drug and continued during the study treatment, or initiated on/after the date of the first dose of study drug and on/before the date of treatment discontinuation.
Measured: From first dose till treatment discontinuation due to any reason (Up to approximately 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Weight
Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.
Measured: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.
Measured: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Temperature
Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.
Measured: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Pulse Rate
Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.
Measured: Baseline and End of Treatment (Up to 107 weeks)
Number of Participants With Post-Baseline Grade Shift in Eastern Cooperative Oncology Group Performance (ECOG) Status
ECOG Scale was used to assess performance status. Grades: 0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory, able to carry out work of light nature. 2: Ambulatory, capable of self-care, unable to carry out work activities. Up and about more than 50% waking hours. 3: Capable of limited self-care, confined to bed/chair more than 50% waking hours. 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed/chair. 5: Dead. Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.
Measured: Baseline and up to End of Treatment (107 weeks)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Reduction of CC-90011
Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Treatment-emergent Adverse Events are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of nivolumab study treatment.
Measured: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Interruption of CC-90011
Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Treatment-emergent Adverse Events are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of nivolumab study treatment.
Measured: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Interruption of Nivolumab
Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Treatment-emergent Adverse Events are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of nivolumab study treatment.
Measured: From the start of study drug until 100 days after last dose of Nivolumab (up to 849 days)
Duration of Response
Duration of Response was defined as the time from the first occurrence of a confirmed documented response to the time of the first documented tumor progression, as determined by Investigator review per RECIST v1.1, or death from any cause, whichever comes first. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression (PD) is defined as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the diameters of new measurable lesions compared to the time of the initial PD.
Measured: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Time to Response
Time to response was defined as the time from the first dose of the study drug to the date of the first confirmed documented response (CR or PR), as assessed by Investigator review per RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression (PD) is defined as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the diameters of new measurable lesions compared to the time of the initial PD.
Measured: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Progression-Free Survival
Progression-Free Survival is the time from first dose of study treatment to the date of the first objectively documented tumor progression as assessed by Investigator review per RECIST v1.1 or death from any cause, whichever occurs first. Disease progression (PD) is defined as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the diameters of new measurable lesions compared to the time of the initial PD.
Measured: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Time to First Subsequent Therapy
Time to First Subsequent Therapy was defined as the time from the first dose of the study drug to the date of the next cancer therapy or death.
Measured: From the first dose of study drug to the date of next cancer therapy or death due to any cause (up to approximately 33 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start14 Jul 2020
- Primary completion19 Dec 2023
- Study completion19 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04350463
- Sponsor's protocol ID
- CC-90011-ST-002
- Other IDs
- U1111-1248-8352, 2019-004194-95, 2019
- Status last verified
- Jan 2025
- First submitted
- 20 Mar 2020
- Last updated
- 22 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Open-label, Multi-cohort Study to Assess Safety and Efficacy of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers
- ClinicalTrials.gov ID
- NCT04350463
- Acronym / sponsor ID
- CC-90011-ST-002
- Conditions
- Neoplasms
- Keywords
- CC-90011, Nivolumab, Advanced Cancers, Small cell lung cancer, Squamous non-small cell lung cancer, LSD1 inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 14 Jul 2020 (actual)
- Primary completion
- 19 Dec 2023 (actual)
- Study completion
- 19 Dec 2023 (actual)
- First posted
- 17 Apr 2020 (actual)
- Results
- Posted 22 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, multicenter, open-label, multi-cohort study to assess safety and efficacy of CC-90011 in combination with nivolumab in subjects with small cell lung cancer or squamous non-small cell lung cancer who have progressed after 1 or 2 lines of therapies.
The primary objectives of the study are to evaluate the overall response rate of subjects treated with CC-90011 in combination with nivolumab in three cohorts:
- Cohort A: SCLC in ICI naïve subjects
- Cohort B: SCLC in ICI progressor subjects
- Cohort C: sqNSCLC in ICI progressor subjects Overall response rate is defined as the proportion of subjects in the treated population who had complete response (CR) or partial response (PR) as assessed by Investigator review per RECIST v1.1.
In Cohort A, expected ORR for nivolumab monotherapy is 14% while target ORR is 30%. To achieve at least 80% power with one-sided type 1 error 0.1, 39 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 12 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 2 or more subjects responding, Cohort A will continue to enroll an additional 27 subjects. If 1 or less subjects respond in stage 1, Cohort A will stop for futility.
In Cohort B and C, expected ORR for nivolumab monotherapy is 5% while target ORR is 15%. To achieve at least 80% power with one-sided type 1 error 0.1, 48 subjects will be enrolled according to a 2-stage group sequential design based on a binomial test. In stage 1, 14 subjects will be enrolled and treated with CC-90011 in combination with nivolumab. If there are 1 or more subjects responding, Cohort B and C will continue to enroll an additional 34 subjects each. If 0 subjects respond in stage 1, Cohort B and C will stop for futility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: SCLC in ICI naïve subjects | Experimental | Drug: CC-90011, Drug: NivolumabCC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle. Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. |
| Cohort B: SCLC in ICI progressor subjects | Experimental | Drug: CC-90011, Drug: NivolumabCC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle. Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. |
| Cohort C: sqNSCLC in ICI progressor subjects | Experimental | Drug: CC-90011, Drug: NivolumabCC-90011 will be given orally (PO) at a dose of 40 mg on a once weekly basis in a continuous 28-day cycle. Nivolumab will be administered intravenously at a dose of 480 mg every 4 weeks per local practice as a 30 minute or a 60-minute infusion as per local practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Subject with histological or cytological confirmation of extensive stage Small Cell Lung Cancer (ES SCLC) or Stage IIIb or IV squamous Non-Small Cell Lung Cancer (sqNSCLC)
- Subject has received 1 or 2 prior lines of therapies, defined as:
- Subject has progressed at the last line of therapy.
- Subject has a measurable disease defined by RECIST v1.1.
Key exclusion criteria (37 listed)
- Subject has not recovered to Grade 2 or lower clinically significant toxicities related to the prior therapy (alopecia excluded).
- Subject has received prior LSD1 therapies.
- Subject has a history of severe hypersensitivity reactions to other monoclonal antibodies
- Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
- Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of the study treatments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-90011CC-90011 | Drug | Arm A: SCLC in ICI naïve subjects, Cohort B: SCLC in ICI progressor subjects, Cohort C: sqNSCLC in ICI progressor subjects |
| NivolumabNivolumab | Drug | Arm A: SCLC in ICI naïve subjects, Cohort B: SCLC in ICI progressor subjects, Cohort C: sqNSCLC in ICI progressor subjects |
Primary outcome
Overall Response Rate
Time frame: Every 6 weeks post Cycle 1 (each cycle is of 28 days) Day 1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participants (up to approximately 33 months)
Overall response rate was defined as the percentage of participants in the treated population who had confirmed complete response (CR) or confirmed partial response (PR) as assessed by Investigator review per RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression (PD) is defined as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the diameters of new measurable lesions compared to the time of the initial PD.
16 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events by Maximal National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Time frame: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Laboratory Results With CTCAE Toxicity Grade >=3 for Hematology Parameters
Time frame: Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 18 (each cycle is of 28 days)
Number of Participants With Laboratory Results With CTCAE Toxicity Grade >=3 for Chemistry Parameters
Time frame: Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 and 18 (Each cycle is of 28 days)
Number of Participants Receiving Concomitant Medication
Time frame: From first dose till treatment discontinuation due to any reason (Up to approximately 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Weight
Time frame: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Temperature
Time frame: Baseline and End of Treatment (Up to 107 weeks)
Change From Baseline at End of Treatment in Vital Sign - Pulse Rate
Time frame: Baseline and End of Treatment (Up to 107 weeks)
Number of Participants With Post-Baseline Grade Shift in Eastern Cooperative Oncology Group Performance (ECOG) Status
Time frame: Baseline and up to End of Treatment (107 weeks)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Reduction of CC-90011
Time frame: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Interruption of CC-90011
Time frame: From the start of study drug through 28 days after the last dose of CC-90011 or until 100 days after last dose of Nivolumab (up to 849 days)
Number of Participants With Treatment-emergent Adverse Events Leading to Dose Interruption of Nivolumab
Time frame: From the start of study drug until 100 days after last dose of Nivolumab (up to 849 days)
Duration of Response
Time frame: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Time to Response
Time frame: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Progression-Free Survival
Time frame: Every 6 weeks post cycle 1 day 1 (each cycle is of 28 days) for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participant (up to approximately 33 months))
Time to First Subsequent Therapy
Time frame: From the first dose of study drug to the date of next cancer therapy or death due to any cause (up to approximately 33 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
37 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CC-90011 and Nivolumab in people with Neoplasms, run by Celgene at 37 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in Spain, United States, France, Italy, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: Every 6 weeks post Cycle 1 (each cycle is of 28 days) Day 1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by participants (up to approximately 33 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.