A Safety Trial of Nivolumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Chemotherapy Regimen (CheckMate153)

• ClinicalTrials.gov Identifier: NCT02066636
• Recruitment Status: Completed
• First Posted: February 19, 2014
• Results First Posted: October 27, 2022
• Last Update Posted: October 27, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: February 14, 2014
• First Posted Date: February 19, 2014
• Results First Submitted Date: September 29, 2022
• Results First Posted Date: October 27, 2022
• Last Update Posted Date: October 27, 2022
• Actual Study Start Date: April 9, 2014
• Actual Primary Completion Date: October 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 29, 2022)

The Number of Participants With Treatment Related Select Adverse Events (Grade 3-4 and Grade 5) [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]

A treatment related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that has a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

• Original Primary Outcome Measures (submitted: February 18, 2014): Incidence for high grade (Grade 3-4 and Grade 5) treatment related select adverse events (AEs) [ Time Frame: Up to 100 days after last dose date (approximately up to 6.5 years) ]

Current Secondary Outcome Measures (submitted: September 29, 2022)

• Median Time to Onset of Select Adverse Events (Grade 3-5) [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  The time from first dose to the first occurrence of any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
• Median Time to Resolution of Select Adverse Events (Grade 3-5) [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  The time from the onset of any select adverse event of interest to its resolution or stabilization. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
• The Number of Participants Who Received Immune Modulating Medication (or Hormonal Replacement Therapy) for Any Grade Select Adverse Events [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  The number of participants receiving medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
• The Number of Participants Who Received ≥ 40 mg Prednisone Equivalents for Any Grade Select Adverse Events [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  The number of participants receiving > 40mg prednisone equivalents for any select adverse event of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
• The Total Duration of All Immune Modulating Medications for Any Grade Select Adverse Events [ Time Frame: From first dose first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  The duration of time participants received medication meant to trigger an immune response for any select Adverse events of interest. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.
• The Number of Participants With High Grade (Grade 3-4 and Grade 5) Select Adverse Events [ Time Frame: From first dose and 100 days after last dose (last dose up to randomization for cohort B) (up to approximately 88 months) ]
  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. The select AEs categories are those that are expected to be most commonly used to describe pneumonitis, interstitial nephritis, diarrhea/colitis, hepatitis, rash, and endocrinopathies and hypersensitivity/infusion reactions. AEs are graded according to NCI CTCAE (Version 4.0) guidelines where Grade 3= Severe, Grade 4 = Life-threatening, Grade 5 = Death.

Original Secondary Outcome Measures (submitted: February 18, 2014)

• Incidence for high grade (Grade 3-4 and Grade 5) select AEs [ Time Frame: Up to 100 days after last dose date (approximately up to 6.5 years) ]
• Median time to onset and median time to resolution (Grade 3-4) [ Time Frame: Up to 100 days after last dose date (approximately up to 6.5 years) ]
• Percentage of subjects who received immune modulating medication or hormonal replacement therapy, percentage of subjects who received ≥40 mg Prednisone equivalents, total duration of all immune modulating medications given for select event [ Time Frame: Up to 100 days after last dose date (approximately up to 6.5 years) ]
  Immune modulating medication (e.g. corticosteroids, Infliximab, Cyclophosphamide, intravenous immune globulin (IVIG), and Mycophenolate Mofetil)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety Trial of Nivolumab in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Chemotherapy Regimen
• Official Title: A Phase IIIb/IV Safety Trial of Nivolumab (BMS-936558) in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed During or After Receiving At Least One Prior Systemic Regimen
• Brief Summary: The purpose of this study is to estimate the incidence and characterize the outcome of high grade, select adverse events in subjects with advanced or metastatic NSCLC treated with Nivolumab.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer (NSCLC)

Intervention

Drug: Nivolumab

Other Name: BMS-936558

Study Arms

• Experimental: Cohort A: Nivolumab
  Nivolumab 3 mg/kg solution intravenous infusion over 30 minutes every two weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent
  Intervention: Drug: Nivolumab
• Experimental: Cohort B: Nivolumab

  Nivolumab 3 mg/kg solution intravenous infusion over 30 minutes every two weeks until 1 year (52 weeks).

  Discontinue treatment and at progression, retreatment allowed

  Intervention: Drug: Nivolumab

• Publications *: Spigel DR, McCleod M, Jotte RM, Einhorn L, Horn L, Waterhouse DM, Creelan B, Babu S, Leighl NB, Chandler JC, Couture F, Keogh G, Goss G, Daniel DB, Garon EB, Schwartzberg LS, Sen R, Korytowsky B, Li A, Aanur N, Hussein MA. Safety, Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non-Small Cell Lung Cancer, Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153). J Thorac Oncol. 2019 Sep;14(9):1628-1639. doi: 10.1016/j.jtho.2019.05.010. Epub 2019 May 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 29, 2022): 1428
• Original Estimated Enrollment (submitted: February 18, 2014): 780
• Actual Study Completion Date: October 6, 2021
• Actual Primary Completion Date: October 6, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Target Population

• Subjects with histologically-or cytologically-documented NSCLC [squamous (SQ) or nonsquamous (NSQ)] who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiotherapy for locally advanced disease)
• Subjects must have experienced disease progression or recurrence during or after at least one systemic therapy for advanced or metastatic disease
• Each subsequent line of therapy must be preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy
• Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy
• Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible
• Subjects with recurrent disease >6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence are eligible
• Subjects with non-squamous histology must be tested for Epithelial Growth Factor Receptor (EGFR) mutations (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution) and Anaplastic Lymphoma Kinase (ALK) rearrangement if tests have not been previously performed. Subjects with progressive disease during or after EGFR or ALK tyrosine kinase inhibitor (TKI) regimens are eligible. Subjects are eligible if genetic test results are indeterminate or if no tumor tissue is available or accessible for testing as long as they have received one prior systemic therapy
• Experimental therapies when given as separate regimen are considered as separate line of therapy
• Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria (radiographic tumor assessment performed within 28 days of first dose of study drug) or clinically apparent disease that the investigator can follow for response per RECIST 1.1
• Eastern Cooperative Oncology Arm (ECOG) performance status (PS)
• PS 0 to 1
• PS 2

Exclusion Criteria:

1. Target Disease Exceptions

   • Subjects with active central nervous system (CNS) metastases are excluded
   • Subjects with carcinomatous meningitis

2. Medical History and Concurrent Diseases

   • Subjects with a history of interstitial lung disease
   • Subjects with active, known or suspected autoimmune disease
   • Subject whom participated in either arm of the following clinical trials CA209-017, CA209-057, CA209-026, and CA184-104 or received prior treatment with anti-programmed death 1 (PD-1) or anti-programmed death-ligand 1 (PDL1) experimental agents

3. Prohibited Treatments and/or Restricted Therapies

   • Ongoing or planned administration of anti-cancer therapies other than those specified in this study
   • Use of corticosteroids or other immunosuppressive medications

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02066636
• Other Study ID Numbers: CA209-153
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: September 2022