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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04350463

Studienbeginn:
Juli 2020

Letztes Update:
02.03.2021

Wirkstoff:
CC-90011, Nivolumab

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Celgene

Collaborator:
-

Studienleiter

Ileana Elias, Medical Director
Study Director
Celgene

Kontakt

Associate Director, Clinical Trial Disclosure
Kontakt:
Phone: 1-888-260-1599
E-Mail: clinicaltrialdisclosure@celgene.com
» Kontaktdaten anzeigen

Studienlocations (3 von 41)

Augusta University - Georgia Cancer Center
30912 Augusta
United StatesNoch nicht rekrutierend» Google-Maps
Investigative Clinical Research of Indiana, LLC
46260 Indianapolis
United StatesNoch nicht rekrutierend» Google-Maps
Memorial Sloan-Kettering Cancer Center - David H. Koch Center for Cancer Care
10021 New York
United StatesNoch nicht rekrutierend» Google-Maps
Novant Health Presbyterian Medical Center
28204 Charlotte
United StatesNoch nicht rekrutierend» Google-Maps
Piedmont Hematology Oncology Associates
27103 Winston-Salem
United StatesNoch nicht rekrutierend» Google-Maps
Gabrail Cancer Center Research
44718 Canton
United StatesRekrutierend» Google-Maps
University Hospitals Cleveland Medical Center
44106 Cleveland
United StatesNoch nicht rekrutierend» Google-Maps
University of Pittsburgh Medical Center
15232 Pittsburgh
United StatesRekrutierend» Google-Maps
Brooke Army Medical Center Francis Street Medical Center
78235-8200 Fort Sam Houston
United StatesRekrutierend» Google-Maps
Virginia Cancer Specialists, PC
22031 Fairfax
United StatesRekrutierend» Google-Maps
Hopital Louis Pradel
69500 Lyon Cedex
FranceNoch nicht rekrutierend» Google-Maps
CHU Nantes Hopital Nord Laennec
44800 Saint-Herblain
FranceRekrutierend» Google-Maps
Centro di Riferimento Oncologico
33081 Aviano
ItalyRekrutierend» Google-Maps
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori (I.R.S.T.)
47014 Meldola
ItalyNoch nicht rekrutierend» Google-Maps
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan
ItalyRekrutierend» Google-Maps
Policlinico Universitario Campus Biomedico Di Roma
00128 Roma
ItalyNoch nicht rekrutierend» Google-Maps
Azienda Ospedaliera Universitaria Integrata di Verona
37134 Verona
ItalyNoch nicht rekrutierend» Google-Maps
Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akcyjna
90-242 Lodz
PolandNoch nicht rekrutierend» Google-Maps
Instytut Centrum Zdrowia Matki Polki
93-338 Lodz
PolandNoch nicht rekrutierend» Google-Maps
Med Polonia Sp. z o.o. NSZOZ
60-693 Poznan
PolandNoch nicht rekrutierend» Google-Maps
Maria Sklodowska-Curie National Research Institute of Oncology
02-781 Warsaw
PolandNoch nicht rekrutierend» Google-Maps
Hospital Universitari Germans Trias i Pujol Can Ruti
08916 Badalona (Barcelona)
SpainRekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Complejo Universitario La Coruna
15006 La Coruna
SpainNoch nicht rekrutierend» Google-Maps
Insular-Maternal and Child University Hospital Complex
35016 Las Palmas de Gran Canaria
SpainNoch nicht rekrutierend» Google-Maps
Hospital Universitario Fundacion Jimenez Diaz
28040 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario 12 de Octubre
28041 Madrid
SpainRekrutierend» Google-Maps
Hospital Puerta de Hierro
28222 Majadahonda, Madrid
SpainNoch nicht rekrutierend» Google-Maps
Clinica Universidad de Navarra
31008 Pamplona
SpainRekrutierend» Google-Maps
Hospital General de Valencia
46014 Valencia
SpainNoch nicht rekrutierend» Google-Maps
Hospital Universitari i Politecnic La Fe de Valencia
46026 Valencia
SpainRekrutierend» Google-Maps
Clatterbridge Centre for Oncology NHS Trust
CH63 4JY Bebington, Wirral
United KingdomNoch nicht rekrutierend» Google-Maps
The Royal Marsden Hospital
SW3 6JJ London
United KingdomRekrutierend» Google-Maps
The Christie NHS Foundation Trust
M20 4BX Manchester
United KingdomNoch nicht rekrutierend» Google-Maps
Royal Marsden Hospital
SM2 5PT Sutton-Surrey
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Overall response rate (Time Frame - Up to 24 months):
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:

1. Adverse Events (AEs) (Time Frame - Up to 24 months):
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 (Time Frame - Up to 24 months):
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 (Time Frame - Up to 24 months):
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. Overall Survival (Time Frame - Up to 48 months):
The time from the first dose of the study drug to the date of death due to any cause.

5. Time to Response (Time Frame - Up to 24 months):
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.

6. Time to first subsequent therapy (Time Frame - Up to 48 months):
The time from the first dose of the study drug to the date of the next cancer therapy or death.

Studien-Arme

  • 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.
  • 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.
  • 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.

Geprüfte Regime

  • CC-90011:
    CC-90011
  • Nivolumab:
    Nivolumab

Quelle: ClinicalTrials.gov


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