A Safety and Efficacy Study of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers

Completed · Phase 2

Conditions studied: Neoplasms

In brief

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.

Key facts

Study ID

NCT04350463

Run by

Celgene

People needed

92

Starts

2020-07-14

Expected to finish

2023-12-19

Last updated by the study team

2025-01-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• 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

You may not qualify if…

• 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.
• 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).

Where it is running

• Local Institution - 102 — Indianapolis, Indiana, United States
• Local Institution - 106 — New York, New York, United States
• Local Institution - 105 — Canton, Ohio, United States
• Local Institution - 104 — Cleveland, Ohio, United States
• Local Institution - 109 — Pittsburgh, Pennsylvania, United States
• Local Institution - 107 — Fort Sam Houston, Texas, United States
• Local Institution - 110 — Houston, Texas, United States
• Local Institution - 111 — Fairfax, Virginia, United States
• Local Institution - 156 — Lyon, France
• Local Institution - 153 — Marseille, France
• Local Institution - 154 — Rennes, France
• Local Institution - 151 — Saint-Herblain, France
• Local Institution - 152 — Villejuif, France
• Local Institution - 301 — Aviano, Italy
• Local Institution - 306 — Meldola, Italy
• Local Institution - 303 — Milan, Italy
• Local Institution - 305 — Roma, Italy
• Local Institution - 304 — Verona, Italy
• Local Institution - 451 — Lodz, Poland
• Local Institution - 452 — Lodz, Poland
• Local Institution - 454 — Poznan, Poland
• Local Institution - 453 — Warsaw, Poland
• Local Institution - 361 — A Coruña, Spain
• Local Institution - 351 — Badalona (Barcelona), Spain
• Local Institution - 355 — Barcelona, Spain

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.