An Investigational Immuno-therapy Study to Test Combination Treatments in Patients With Advanced Non-Small Cell Lung Cancer (FRACTION-Lung)

• ClinicalTrials.gov Identifier: NCT02750514
• Recruitment Status: Terminated
• First Posted: April 25, 2016
• Results First Posted: March 22, 2021
• Last Update Posted: March 22, 2021
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: April 21, 2016
• First Posted Date: April 25, 2016
• Results First Submitted Date: January 27, 2021
• Results First Posted Date: March 22, 2021
• Last Update Posted Date: March 22, 2021
• Actual Study Start Date: May 9, 2016
• Actual Primary Completion Date: January 29, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 23, 2021)

• Objective Response Rate (ORR) [ Time Frame: From first dose to 2 years following last dose (up to 30 months) ]
  ORR is defined as the percentage of participants whose confirmed best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR was assessed by investigator per RECIST1.1. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.
• Duration of Response (DOR) [ Time Frame: From first dose to 2 years following last dose (up to 30 months) ]
  DOR, computed for all treated participants with a confirmed BOR of CR or PR, is defined as the time between the date of first response and the date of first documented disease progression (as determined by RECIST 1.1) or death due to any cause. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.
• Progression Free Survival Rate (PFSR) at 24 Weeks [ Time Frame: From first dose to 24 weeks after first dose ]
  The PFSR at 24 weeks is defined as the proportion of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. Results are presented by study track. Track 1 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 positive (>=1%) Track 2 = participants naive for prior immuno-oncology (IO) therapy and PD-L1 negative (<1%) Track 3 = participants with prior anti-PD-1/PD-L1 therapy Track 4 = participants naive for prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3) Track 5 = participants with prior anti-PD-1/PD-L1 therapy (established upon enrollment closure of tracks 1,2 and 3). Results for each study track are presented only for treatment groups who received a treatment in that specific track.

Original Primary Outcome Measures (submitted: April 22, 2016)

• Objective Response Rate (ORR) [ Time Frame: 24 weeks ]
• Duration of Response (DOR) [ Time Frame: 24 weeks ]
• Progression-free Survival Rate (PFSR) [ Time Frame: 24 weeks ]

Current Secondary Outcome Measures (submitted: February 23, 2021)

• Percentage of Participants Experiencing Adverse Events (AEs) [ Time Frame: From first dose to 100 days following last dose ]
  This outcome measure describes the percentage of participants who experienced any grade, all causality AEs during the specified time frame
• Percentage of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: From first dose to 100 days following last dose ]
  This outcome measure describes the percentage of participants who experienced any grade, all causality SAEs during the specified time frame
• Percentage of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [ Time Frame: From first dose to 100 days following last dose ]
  This outcome measure describes the percentage of participants who experienced all causality AEs leading to discontinuation of study therapy during the specified time frame
• Percentage of Participants Experiencing Death [ Time Frame: From first dose to up to 45 months following first dose ]
  This outcome measure describes the percentage of participants who died (due to any cause) during the specified time frame
• Number of Participants Experiencing Laboratory Abnormalities in Hepatic Tests [ Time Frame: From first dose to 100 days following last dose (approximately 9 months) ]
  The following measurements will be considered laboratory abnormalities for hepatic tests:

  • ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN
  • Total bilirubin > 2 x ULN
  • Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN
  • Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN ALT=Alanine aminotransferase AST=Aspartate aminotransferase ULN=Upper Limit of Normal
• Number of Participants Experiencing Laboratory Abnormalities in Thyroid Tests [ Time Frame: From first dose to 100 days following last dose (approximately 9 months) ]
  The following measurements will be considered laboratory abnormalities for thyroid tests:

  • TSH value > ULN and
  • With baseline TSH value ≤ ULN
  • At least one T3/T4 test value < LLN
  • Low TSH < LLN and
  • With baseline TSH value ≥ LLN
  • At least one T3/T4 test value > ULN TSH = thyroid stimulating hormone ULN=Upper Limit of Normal LLN=Lower Limit of Normal T3=Triiodothyronine T4=Thyroxine

Original Secondary Outcome Measures (submitted: April 22, 2016)

• Safety and tolerability of Nivolumab based on incidence of adverse events, serious adverse events, adverse events leading to discontinuation and deaths [ Time Frame: approximately 38 weeks ]
• Safety and tolerability of Nivolumab & Dasatinib combination based on incidence of adverse events, serious adverse events, adverse events leading to discontinuation and deaths [ Time Frame: approximately 38 weeks ]
• Safety and tolerability of Nivolumab & BMS-986016 combination based on incidence of adverse events, serious adverse events, adverse events leading to discontinuation and deaths [ Time Frame: approximately 38 weeks ]

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

Descriptive Information

• Brief Title: An Investigational Immuno-therapy Study to Test Combination Treatments in Patients With Advanced Non-Small Cell Lung Cancer
• Official Title: A Phase 2, Fast Real Time Assessment of Combination Therapies in Immuno-Oncology Study in Subjects With Advanced Non-Small Cell Lung Cancer (FRACTION-Lung)
• Brief Summary: The purpose of this study is to determine whether Nivolumab, in combination with other therapies, is effective in patients with advanced Non-Small Cell lung cancer
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Cancer

Intervention

• Biological: Nivolumab
  Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator.
  Other Names:

  • BMS-936558
  • MDX-1106
  • OPDIVO
• Drug: Dasatinib
  Other Names:

  • BMS-354825
  • SPRYCEL
• Biological: Relatlimab
  Other Name: BMS-986016
• Biological: Ipilimumab
  Other Names:

  • BMS-734016
  • Yervoy
• Drug: BMS-986205
  Specified dose on specified days

Study Arms

• Active Comparator: Nivolumab
  Nivolumab Monotherapy - Arm associated with this intervention is closed. Nivolumab is no longer given as an active comparator
  Intervention: Biological: Nivolumab
• Experimental: Nivolumab & Dasatinib
  Nivolumab in combination with Dasatinib
  Interventions:

  • Biological: Nivolumab
  • Drug: Dasatinib
• Experimental: Nivolumab & Relatlimab
  Nivolumab in combination with Relatlimab
  Interventions:

  • Biological: Nivolumab
  • Biological: Relatlimab
• Experimental: Nivolumab & Ipilimumab
  Nivolumab in combination with Ipilimumab
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Nivolumab & BMS-986205
  Nivolumab in combination with BMS- 986205
  Interventions:

  • Biological: Nivolumab
  • Drug: BMS-986205

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 23, 2021): 295
• Original Estimated Enrollment (submitted: April 22, 2016): 685
• Actual Study Completion Date: January 29, 2020
• Actual Primary Completion Date: January 29, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Advanced Non Small Cell Lung Cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1
• Life expectancy of at least 3 months from most recent chemotherapy or immunotherapy treatment
• Must have at least 1 lesion with measurable disease

Exclusion Criteria:

• Subjects with certain mutations that have not been treated with a targeted therapy prior to enrollment
• Subjects who need daily oxygen therapy
• People with autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply

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: Australia, Austria, Canada, France, Italy, Spain, Switzerland, United States
• Removed Location Countries: Denmark, Netherlands, Norway, Sweden, United Kingdom

Administrative Information

• NCT Number: NCT02750514
• Other Study ID Numbers: CA018-001
• Has Data Monitoring Committee: Yes

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: February 2021