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

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04350463
Collaborator
(none)
92
Enrollment
78
Locations
3
Arms
32.7
Anticipated Duration (Months)
1.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
92 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 14, 2020
Anticipated Primary Completion Date :
Apr 5, 2023
Anticipated Study Completion Date :
Apr 5, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A: SCLC in ICI naïve subjects

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.

Drug: CC-90011
CC-90011

Drug: Nivolumab
Nivolumab
Experimental: Cohort B: SCLC in ICI progressor subjects

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.

Drug: CC-90011
CC-90011

Drug: Nivolumab
Nivolumab
Experimental: Cohort C: sqNSCLC in ICI progressor subjects

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.

Drug: CC-90011
CC-90011

Drug: Nivolumab
Nivolumab

Outcome Measures

Primary Outcome Measures

  1. Overall response rate [Until 100-day safety follow-up of the last participant on treatment]

    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

  1. Adverse Events (AEs) [Until 100-day safety follow-up of the last participant on treatment]

    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.

  2. Duration of response [Until 100-day safety follow-up of the last participant on treatment]

    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.

  3. Progression-free survival [Until 100-day safety follow-up of the last participant on treatment]

    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.

  4. Time to Response [Until 100-day safety follow-up of the last participant on treatment]

    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.

  5. Time to first subsequent therapy [Until 100-day safety follow-up of the last participant on treatment]

    The time from the first dose of the study drug to the date of the next cancer therapy or death.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:

  4. 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

  1. 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)

  1. 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)

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

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

  3. 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.

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

  5. Subject must have the following laboratory values:

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

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

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

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

  10. 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

  11. 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)

  12. 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.

  5. 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.

  6. 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.

  7. 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.

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

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

  10. Subject has any of the following cardiovascular criteria:

  11. Evidence of acute or ongoing cardiac ischemia

  12. Current symptomatic pulmonary embolism

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

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

  15. Persistent or clinically meaningful ventricular arrhythmias prior to enrollment

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

  17. 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)

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

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

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

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

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

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

  24. 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).

  25. 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.

  26. 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.

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

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

  29. 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.

  30. Subject is pregnant or nursing.

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

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

  33. Subject has interstitial lung disease history.

  34. Subject has received a live/attenuated vaccine within 30 days of first dose.

  35. Subject has previous SARS-CoV-2 infection either suspected or confirmed within 4 weeks prior to screening.

  36. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Augusta University - Georgia Cancer Center Augusta Georgia United States 30912
2 Investigative Clinical Research of Indiana, LLC Indianapolis Indiana United States 46260
3 Local Institution - 102 Indianapolis Indiana United States 46260
4 Local Institution - 106 New York New York United States 10021
5 Memorial Sloan-Kettering Cancer Center - David H. Koch Center for Cancer Care New York New York United States 10021
6 Novant Health Presbyterian Medical Center Charlotte North Carolina United States 28204
7 Piedmont Hematology Oncology Associates Winston-Salem North Carolina United States 27103
8 Gabrail Cancer Center Research Canton Ohio United States 44718
9 Local Institution - 105 Canton Ohio United States 44718
10 Local Institution - 104 Cleveland Ohio United States 44106
11 University Hospitals Cleveland Medical Center Cleveland Ohio United States 44106
12 Local Institution - 109 Pittsburgh Pennsylvania United States 15232
13 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15232
14 Brooke Army Medical Center Francis Street Medical Center Fort Sam Houston Texas United States 78235-8200
15 Local Institution - 107 Fort Sam Houston Texas United States 78235-8200
16 Local Institution - 110 Houston Texas United States 77090
17 Millennium Oncology Houston Texas United States 77090
18 Local Institution - 111 Fairfax Virginia United States 22031
19 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
20 Hopital Louis Pradel Lyon Cedex France 69500
21 Local Institution - 156 Lyon Cedex France 69500
22 Hospital Le Timone Marseille Cedex 5 France 13385
23 Local Institution - 153 Marseille Cedex 5 France 13385
24 Hospital Pontchaillou Rennes France 35033
25 Local Institution - 154 Rennes France 35033
26 CHU Nantes Hopital Nord Laennec Saint-Herblain France 44800
27 Local Institution - 151 Saint-Herblain France 44800
28 Gustave Roussy Villejuif CEDEX France 94805
29 Local Institution - 152 Villejuif CEDEX France 94805
30 Centro di Riferimento Oncologico Aviano Italy 33081
31 Local Institution - 301 Aviano Italy 33081
32 Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.) Meldola Italy 47014
33 Local Institution - 306 Meldola Italy 47014
34 Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy 20133
35 Local Institution - 303 Milan Italy 20133
36 Local Institution - 305 Roma Italy 00128
37 Policlinico Universitario Campus Biomedico Di Roma Roma Italy 00128
38 Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy 37134
39 Local Institution - 304 Verona Italy 37134
40 Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna Lodz Poland 90-242
41 Local Institution - 451 Lodz Poland 90-242
42 Instytut Centrum Zdrowia Matki Polki Lodz Poland 93-338
43 Local Institution - 452 Lodz Poland 93-338
44 Local Institution - 454 Poznan Poland 60-693
45 Med Polonia Sp. z o.o. NSZOZ Poznan Poland 60-693
46 Local Institution - 453 Warsaw Poland 02-781
47 Maria Sklodowska-Curie National Research Institute of Oncology Warsaw Poland 02-781
48 Hospital Universitari Germans Trias i Pujol Can Ruti Badalona (Barcelona) Spain 08916
49 Local Institution - 351 Badalona (Barcelona) Spain 08916
50 Hospital Quiron Barcelona Barcelona Spain 08023
51 Local Institution - 355 Barcelona Spain 08023
52 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
53 Local Institution - 356 Barcelona Spain 08035
54 Complejo Universitario La Coruna La Coruna Spain 15006
55 Local Institution - 361 La Coruna Spain 15006
56 Insular-Maternal and Child University Hospital Complex Las Palmas de Gran Canaria Spain 35016
57 Local Institution - 359 Las Palmas de Gran Canaria Spain 35016
58 Clinica Universidad de Navarra Madrid Spain 28027
59 Local Institution - 358 Madrid Spain 28027
60 Hospital Universitario Fundacion Jimenez Diaz Madrid Spain 28040
61 Local Institution - 353 Madrid Spain 28040
62 Hospital Universitario 12 de Octubre Madrid Spain 28041
63 Local Institution - 357 Madrid Spain 28041
64 Hospital Puerta de Hierro Majadahonda, Madrid Spain 28222
65 Local Institution - 360 Majadahonda, Madrid Spain 28222
66 Clinica Universidad de Navarra Pamplona Spain 31008
67 Local Institution - 352 Pamplona Spain 31008
68 Hospital General de Valencia Valencia Spain 46014
69 Local Institution - 362 Valencia Spain 46014
70 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain 46026
71 Local Institution - 354 Valencia Spain 46026
72 Clatterbridge Centre for Oncology NHS Trust Bebington, Wirral United Kingdom CH63 4JY
73 Local Institution - 254 London United Kingdom SW3 6JJ
74 The Royal Marsden Hospital London United Kingdom SW3 6JJ
75 Local Institution - 251 Manchester United Kingdom M20 4BX
76 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
77 Local Institution - 255 Sutton-Surrey United Kingdom SM2 5PT
78 Royal Marsden Hospital Sutton-Surrey United Kingdom SM2 5PT

Sponsors and Collaborators

  • Celgene

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT04350463
Other Study ID Numbers:
  • CC-90011-ST-002
  • U1111-1248-8352
  • 2019-004194-95
First Posted:
Apr 17, 2020
Last Update Posted:
Aug 1, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Celgene
CC-90011
Nivolumab
Advanced Cancers
Small cell lung cancer
Squamous non-small cell lung cancer
LSD1 inhibitor
Additional relevant MeSH terms:
Nivolumab
Pulrodemstat besilate

Study Results

No Results Posted as of Aug 1, 2022