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

NCT04350463 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CC-90011-ST-002U1111-1248-83522019-004194-95
• Study Type: interventional
• Target: 92
• Locations: 6 countries
• Sites: 37

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.

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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

  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

  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

  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 and End of Treatment (Up to 107 weeks)

Study Arms (3)

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.

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.

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.

Drug: CC-90011; Drug: Nivolumab

Interventions

CC-90011 DRUG

CC-90011

Arm A: SCLC in ICI naïve subjects; Cohort B: SCLC in ICI progressor subjects; Cohort C: sqNSCLC in ICI progressor subjects

Nivolumab DRUG

Nivolumab

Arm A: SCLC in ICI naïve subjects; Cohort B: SCLC in ICI progressor subjects; Cohort C: sqNSCLC in ICI progressor subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Celgene: lead

Study Sites (37)

Local Institution - 102

Indianapolis, Indiana, 46260, United States

Location

Local Institution - 106

New York, New York, 10021, United States

Location

Local Institution - 105

Canton, Ohio, 44718, United States

Location

Local Institution - 104

Cleveland, Ohio, 44106, United States

Location

Local Institution - 109

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 107

Fort Sam Houston, Texas, 78235-8200, United States

Location

Local Institution - 110

Houston, Texas, 77090, United States

Location

Local Institution - 111

Fairfax, Virginia, 22031, United States

Location

Local Institution - 156

Lyon, 69500, France

Location

Local Institution - 153

Marseille, 13385, France

Location

Local Institution - 154

Rennes, 35033, France

Location

Local Institution - 151

Saint-Herblain, 44800, France

Location

Local Institution - 152

Villejuif, 94805, France

Location

Local Institution - 301

Aviano, 33081, Italy

Location

Local Institution - 306

Meldola, 47014, Italy

Location

Local Institution - 303

Milan, 20133, Italy

Location

Local Institution - 305

Roma, 00128, Italy

Location

Local Institution - 304

Verona, 37134, Italy

Location

Local Institution - 451

Lodz, 90-242, Poland

Location

Local Institution - 452

Lodz, 93-338, Poland

Location

Local Institution - 454

Poznan, 60-693, Poland

Location

Local Institution - 453

Warsaw, 02-781, Poland

Location

Local Institution - 361

A Coruña, 15006, Spain

Location

Local Institution - 351

Badalona (Barcelona), 08916, Spain

Location

Local Institution - 355

Barcelona, 08023, Spain

Location

Local Institution - 356

Barcelona, 08035, Spain

Location

Local Institution - 359

Las Palmas de Gran Canaria, 35016, Spain

Location

Local Institution - 358

Madrid, 28027, Spain

Location

Local Institution - 353

Madrid, 28040, Spain

Location

Local Institution - 357

Madrid, 28041, Spain

Location

Local Institution - 360

Majadahonda, Madrid, 28222, Spain

Location

Local Institution - 352

Pamplona, 31008, Spain

Location

Local Institution - 362

Valencia, 46014, Spain

Location

Local Institution - 354

Valencia, 46026, Spain

Location

Local Institution - 254

London, SW3 6JJ, United Kingdom

Location

Local Institution - 251

Manchester, M20 4BX, United Kingdom

Location

Local Institution - 255

Sutton-Surrey, SM2 5PT, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasms; Small Cell Lung Carcinoma

Interventions

pulrodemstat besilate; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: April 17, 2020
• Study Start: July 14, 2020
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2025-01

Locations

IT (5); FR (5); PL (4); GB (3); US (8); ES (12)