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

NCT04350463

Description:

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.

Related Conditions:
  • Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Efficacy Study of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers
  • Official Title: A Phase 2, Multicenter, Open-label, Multi-cohort Study to Assess Safety and Efficacy of CC-90011 in Combination With Checkpoint Inhibitor(s) in Subjects With Advanced Cancers

Clinical Trial IDs

  • ORG STUDY ID: CC-90011-ST-002
  • SECONDARY ID: U1111-1248-8352
  • SECONDARY ID: 2019-004194-95
  • NCT ID: NCT04350463

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
CC-90011Arm A: SCLC in ICI naïve subjects
NivolumabArm A: SCLC in ICI naïve subjects

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: SCLC in ICI naïve subjectsExperimentalCC-90011 will be given orally (PO) at a dose of 60 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.
  • CC-90011
  • Nivolumab
Cohort B: SCLC in ICI progressor subjectsExperimentalCC-90011 will be given orally (PO) at a dose of 60 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.
  • CC-90011
  • Nivolumab
Cohort C: sqNSCLC in ICI progressor subjectsExperimentalCC-90011 will be given orally (PO) at a dose of 60 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.:
  • CC-90011
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).

          2. 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)

          3. Subject has received 1 or 2 prior lines of therapies, defined as:

               1. 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

               2. 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)

               3. 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)

          4. Subject has progressed at the last line of therapy.

          5. Subject has a measurable disease defined by RECIST v1.1.

          6. 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.

          7. Subject has ECOG Performance Status of 0 to 1.

          8. Subject must have the following laboratory values:

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               2. Hemoglobin (Hgb) ≥ 9 g/dL (one-time blood transfusion is allowed)

               3. Platelet (Plt) Count ≥ 150 x 109/L

               4. White blood cells (WBC) ≥ 2 x 109L

               5. 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

               6. 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)

               7. 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

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. Subject has not recovered to Grade 2 or lower clinically significant toxicities
             related to the prior therapy (alopecia excluded).

          2. Subject has received prior LSD1 therapies.

          3. Subject has a history of severe hypersensitivity reactions to other monoclonal
             antibodies

          4. Subject with symptomatic and untreated or unstable central nervous system (CNS)
             metastases.

               1. 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.

               2. 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.

          5. 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.

          6. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly
             those with a history of and/or risk of perforation and GI tract hemorrhages.

          7. Subject with any hemorrhage/bleeding event > NCI CTCAE Grade 2 or haemoptysis > 1
             teaspoon within 4 weeks prior to the first dose.

          8. Subject has any of the following cardiovascular criteria:

               1. Evidence of acute or ongoing cardiac ischemia

               2. Current symptomatic pulmonary embolism

               3. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to enrollment

               4. Heart failure of New York Heart Association Classification III or IV ≤ 6 months
                  prior to enrollment

               5. Persistent or clinically meaningful ventricular arrhythmias prior to enrollment

               6. Cerebral vascular accident or transient ischemic attack ≤ 6 months prior to
                  enrollment

               7. 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)

               8. A history of additional risk factors for Torsades de pointes (TdP) (eg, heart
                  failure, hypokalemia, family history of Long QT Syndrome)

               9. Uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg)

          9. Subject has known human immunodeficiency virus (HIV) infection.

         10. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.

               1. Subject who is seropositive due to HBV vaccination is eligible.

               2. Subject who has no active viral infection and is under adequate prophylaxis
                  against HBV reactivation is eligible.

         11. 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).

         12. 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.

               1. 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.

               2. Adrenal replacement steroid doses ≤ 10 mg daily prednisone or equivalent are
                  permitted in the absence of active autoimmune disease.

               3. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
                  (with minimal systemic absorption) are permitted.

         13. 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.

         14. Subject is pregnant or nursing.

         15. Subject has a history of persistent skin rash ≥ NCI CTCAE Grade 2 related to prior ICI
             therapy.

         16. Subject has organ transplant history, including allogeneic stem cell transplant.

         17. Subject has severe infection requiring a parenteral antibiotic treatment.

         18. Subject has interstitial lung disease history.

         19. Subject has received a live/attenuated vaccine within 30 days of first dose.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 24 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:Up to 24 months
Safety Issue:
Description:An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. All adverse events will be collected and collated according to grade and frequency. This will include all events considered related or unrelated to study therapy.
Measure:Duration of response
Time Frame:Up to 24 months
Safety Issue:
Description:Every 6 weeks post C1D1 for the first 24 weeks and then every 8 weeks until disease progression, new anticancer therapy, death or withdrawal by subject.
Measure:Progression-free survival
Time Frame:Up to 24 months
Safety Issue:
Description:The time from the first dose of the study drug 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.
Measure:Overall Survival
Time Frame:Up to 48 months
Safety Issue:
Description:The time from the first dose of the study drug to the date of death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • CC-90011
  • Nivolumab
  • Advanced Cancers
  • Small cell lung cancer
  • Squamous non-small cell lung cancer
  • LSD1 inhibitor

Last Updated

April 27, 2020