A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT01928394
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2013
• Results First Posted: March 24, 2020
• Last Update Posted: April 18, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: August 21, 2013
• First Posted Date: August 23, 2013
• Results First Submitted Date: February 5, 2020
• Results First Posted Date: March 24, 2020
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: October 24, 2013
• Actual Primary Completion Date: February 5, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2020)

Objective Response Rate ( ORR ) [ Time Frame: 60 months ]

The number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants.

Original Primary Outcome Measures (submitted: August 21, 2013)

Objective response rate (ORR) in all assigned subjects as determined by the investigators [ Time Frame: Up until time of first documented tumor progression or death (approximately up to 17 months) ]

ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of assigned subjects

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: August 21, 2013): Rate of treatment-related adverse events (AEs) leading to drug discontinuations during the first 12 weeks of treatment [ Time Frame: Up to Week 12 of treatment ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors
• Official Title: A Phase 1/2, Open-label Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab in Subjects With Advanced or Metastatic Solid Tumors
• Brief Summary: To investigate the safety and efficacy of nivolumab as a single agent or in combination with ipilimumab in 6 tumor types - triple-negative breast cancer (TNBC), gastric cancer (GC), pancreatic adenocarcinoma (PC), small cell lung cancer (SCLC), bladder cancer (BC), and ovarian cancer (OC). A combination of nivolumab with ipilimumab and cobimetinib is also investigated in PC.

Detailed Description

All tumor types are now closed for enrollment:

Triple Negative Breast Cancer

Gastric Cancer

Pancreatic Cancer

Small Cell Lung Cancer

Bladder Cancer

Ovarian Cancer

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Solid Tumors

Intervention

• Biological: Nivolumab
  Other Names:

  • BMS-936558
  • MDX-1106
• Biological: Ipilimumab
  Other Names:

  • Yervoy
  • BMS-734016
  • MDX-010
• Drug: Cobimetinib
  Other Name: Cotellic

Study Arms

• Experimental: Arm N - Nivolumab
  Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Intervention: Biological: Nivolumab
• Experimental: Arm N-I, Level 1: Nivolumab+Ipilimumab
  Nivolumab 1 mg/kg solution intravenously plus Ipilimumab 1 mg/kg solution every 3 weeks for 4 doses followed by Nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Arm N-I, Level 2: Nivolumab+Ipilimumab
  Nivolumab 1 mg/kg solution intravenously plus Ipilimumab 3 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Arm N-I, Level 2b: Nivolumab+Ipilimumab
  Nivolumab 3 mg/kg solution intravenously plus Ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Arm N-I, Level 2c: Nivolumab+Ipilimumab
  Nivolumab 3 mg/kg solution intravenously every 3 weeks combined with ipilimumab 1 mg/kg every 6 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
• Experimental: Arm N-I, Level 2d: Nivolumab+Ipilimumab+Cobimetinib
  Nivolumab 3 mg/kg solution intravenously every 3 weeks combined with ipilimumab 1 mg/kg every 6 weeks and cobimetinib 60mg once daily 21days on/7 days off until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab
  • Drug: Cobimetinib

Publications *

• Sharma P, Siefker-Radtke A, de Braud F, Basso U, Calvo E, Bono P, Morse MA, Ascierto PA, Lopez-Martin J, Brossart P, Rohrberg K, Mellado B, Fischer BS, Meadows-Shropshire S, Abdel Saci, Callahan MK, Rosenberg J. Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. J Clin Oncol. 2019 Jul 1;37(19):1608-1616. doi: 10.1200/JCO.19.00538. Epub 2019 May 17. Erratum In: J Clin Oncol. 2019 Aug 10;37(23):2094.
• Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. doi: 10.1200/JCO.2017.76.6212. Epub 2018 Aug 15. Erratum In: J Clin Oncol. 2019 Feb 10;37(5):443.
• Teo MY, Seier K, Ostrovnaya I, Regazzi AM, Kania BE, Moran MM, Cipolla CK, Bluth MJ, Chaim J, Al-Ahmadie H, Snyder A, Carlo MI, Solit DB, Berger MF, Funt S, Wolchok JD, Iyer G, Bajorin DF, Callahan MK, Rosenberg JE. Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers. J Clin Oncol. 2018 Jun 10;36(17):1685-1694. doi: 10.1200/JCO.2017.75.7740. Epub 2018 Feb 28.
• Sharma P, Callahan MK, Bono P, Kim J, Spiliopoulou P, Calvo E, Pillai RN, Ott PA, de Braud F, Morse M, Le DT, Jaeger D, Chan E, Harbison C, Lin CS, Tschaika M, Azrilevich A, Rosenberg JE. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016 Nov;17(11):1590-1598. doi: 10.1016/S1470-2045(16)30496-X. Epub 2016 Oct 9. Erratum In: Lancet Oncol. 2019 Feb;20(2):e71.
• Antonia SJ, Lopez-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jager D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin CS, Christensen O, Calvo E. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-895. doi: 10.1016/S1470-2045(16)30098-5. Epub 2016 Jun 4. Erratum In: Lancet Oncol. 2016 Jul;17 (7):e270. Lancet Oncol. 2019 Feb;20(2):e70.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 21, 2022): 1163
• Original Estimated Enrollment (submitted: August 21, 2013): 160
• Estimated Study Completion Date: December 31, 2023
• Actual Primary Completion Date: February 5, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects with histologically or cytologically confirmed locally advanced or metastatic disease of the following tumor types:
• Triple Negative Breast Cancer
• Gastric Cancer
• Pancreatic Cancer
• Small Cell Lung Cancer
• Bladder Cancer
• Ovarian Cancer
• Subjects must have measurable disease
• Eastern Cooperative Oncology Group (ECOG) of 0 or 1
• Adequate hematological and organ function as confirmed by laboratory values

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases
• Subjects with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
• Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including Ipilimumab; or other medicines specifically targeting T cell is also prohibited

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, Denmark, Finland, Germany, Italy, Spain, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT01928394
• Other Study ID Numbers: CA209-032; 2013-002844-10 ( EudraCT Number )
• 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: April 2023