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An Investigational Immuno-Therapy Study of Experimental Medication BMS-986277 Given Alone and in Combination With Nivolumab in Epithelial Cancers

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ClinicalTrials.gov Identifier: NCT03363776
Recruitment Status : Terminated (Business objectives have changed)
First Posted : December 6, 2017
Results First Posted : December 19, 2020
Last Update Posted : December 19, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief Summary:
The purpose of this study is to investigate experimental medication BMS-986277 given alone and in combination with Nivolumab in patients with epithelial cancers.

Condition or disease Intervention/treatment Phase
Cancer Biological: BMS-986277 Biological: Nivolumab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2a First in Human Study of BMS-986277 Administered Alone and in Combination With Nivolumab in Advanced Epithelial Tumors
Actual Study Start Date : December 6, 2017
Actual Primary Completion Date : November 22, 2019
Actual Study Completion Date : November 22, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Monotherapy
BMS-986277 administered alone
 Biological: BMS-986277
Specified dose on specified days
Experimental: Combination Dose Escalation Therapy
BMS-986277 administered in combination with Nivolumab
 Biological: BMS-986277
Specified dose on specified days

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-963558
Experimental: Combination Expansion Therapy
BMS-986277 monotherapy with option for subsequent Nivolumab therapy
 Biological: BMS-986277
Specified dose on specified days

Biological: Nivolumab
Specified dose on specified days
Other Names:
  • Opdivo
  • BMS-963558


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With an Adverse Event (AE) [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced an AE during the course of the study.

  2. Number of Participants With a Serious Adverse Event (SAE) [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced a SAE during the course of the study.

  3. Number of Participants With an Adverse Event (AE) Meeting Protocol-defined Dose Limiting Toxicity (DLT) Criteria [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced an AE meeting protocol-defined DLT criteria during the course of the study.

  4. Number of Participants With an Adverse Event (AE) Leading to Discontinuation [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced an AE leading to discontinuation during the course of the study.

  5. Number of Participants With an Adverse Event (AE) Leading to Death [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced an AE leading to death during the course of the study.

  6. Number of Participants With a Clinical Laboratory Test Abnormality [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced a clinical laboratory test abnormality during the course of the study.

  7. Number of Participants With a Vital Sign Abnormality or Other Safety Biomarkers [ Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) ]
    Number of participants who experienced a vital sign abnormality or other safety biomarkers during the course of the study.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: at Weeks 8, 16 and 24 ]

    ORR is defined as the proportion of all treated participants whose BOR is either CR or PR. BOR was determined by investigators for the reported data.

    Estimate of ORR and corresponding 2-sided exact 95% CI using the Clopper-Pearson method


  2. Disease Control Rate (DCR) [ Time Frame: at Weeks 8, 16 and 24 ]

    DCR includes complete response (CR), partial response (PR), and stable disease (SD).

    Estimate of DCR and corresponding 2-sided exact 95% CI using the Clopper-Pearson method


  3. Median Duration of Response (mDOR) [ Time Frame: at Weeks 8, 16 and 24 ]

    DOR for a participant with a BOR of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1/PCWG3 or death, whichever occurs first.

    Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation)


  4. Median Progression-Free Survival (mPFS) [ Time Frame: at Weeks 8, 16 and 24, to progression ]

    PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first.

    Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation) for the median and Greenwood formula for the rate.


  5. Progression-Free Survival Rate (PFSR) [ Time Frame: at Weeks 8, 16 and 24 ]

    PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first.

    Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation) for the median and Greenwood formula for the rate.


  6. Cmax [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Cmax is defined as the maximum observed blood concentration.


  7. Tmax [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Tmax is defined as the time of maximum observed blood concentration.


  8. AUC(0-T) [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    AUC(0-T) is the area under the blood concentration-time curve from time zero to time of last quantifiable concentration.


  9. AUC(INF) [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    AUC(INF) is the area under the blood concentration-time curve from time zero extrapolated to infinite time.


  10. T-HALF [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    T-HALF is defined as the apparent terminal half-life.


  11. CLT [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    CLT is defined as the total body clearance.


  12. Vss [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Vss is defined as the volume of distribution at steady-state.


  13. Vz [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Vz is defined as the volume of distribution of the elimination phase.


  14. AUC(0-48) [ Time Frame: Cycle 1 (from time zero to 48 hours postdose) ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    AUC(0-T) is the area under the blood concentration-time curve from time zero to 48 hours postdose


  15. AUC(0-8) [ Time Frame: Cycle 1 (from time zero to 8 hours postdose) ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    AUC(0-T) is the area under the blood concentration-time curve from time zero to 8 hours postdose


  16. C48 [ Time Frame: Cycle 1 at 48 hours postdose ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    C48 is defined as the blood concentration at 48 hours postdose.


  17. Css-avg [ Time Frame: Cycle 1 (from time zero to 48 hours postdose) ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Css-avg is defined as the average blood concentration over a dosing interval at steady state (AUC[0-48]/48).


  18. AI_AUC [ Time Frame: Cycle 1 (Day 19, Day 15) ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    AUC accumulation index; ratio of AUC(0-48) on Cycle 1 Day 19 to AUC(0-48) on Cycle 1 Day 15 for monotherapy.


  19. AI_Cmax [ Time Frame: Cycle 1 (Day 19, Day 15) ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Cmax accumulation index; ratio of Cmax on Cycle 1 Day 19 to Cmax on Cycle 1 Day 15 for monotherapy.


  20. T-HALFeff [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    T-HALFeff is defined as effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC, Cmax)


  21. Ctrough [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.

    Ctrough is defined as the trough observed blood concentration.


  22. Number of Participants With a Positive Antibody-Drug-Antibody (ADA) Response [ Time Frame: Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits ]

    Baseline ADA-positive participant is defined as a participant who has an ADA-detected sample at baseline.

    ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment.

    Frequency distribution of baseline ADA-positive participants and ADA-positive participants after initiation of the treatment



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion Criteria:

  • Histological or cytological confirmation of metastatic and/or unresectable metastatic colorectal, prostate, pancreatic, breast, ovarian, or urothelial carcinoma with measureable disease for solid tumors per RECIST v1.1 and for prostate carcinoma per PCWG3
  • Presence of at least 2 lesions: at least one with measurable disease as defined by RECIST v1.1 for solid tumors and by PCWG3 for prostate carcinoma for response assessment; at least 1 lesion must be accessible for biopsy in addition to the target lesion
  • Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting, if such a therapy exists, and have been considered for all other potentially efficacious therapies prior to enrollment
  • ECOG performance status less than or equal to 2

Exclusion Criteria:

  • Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease
  • Participants with carcinomatous meningitis
  • Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study treatment
  • Participants with active, known, or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363776


Locations
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United States, South Dakota
Sanford Research
Sioux Falls, South Dakota, United States, 57104
Canada, Ontario
Local Institution
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 1Z5
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] August 15, 2018
Statistical Analysis Plan  [PDF] March 12, 2018

More Information
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Additional Information:

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03363776    
Other Study ID Numbers: CA034-001
2017-002199-24 ( EudraCT Number )
First Posted: December 6, 2017    Key Record Dates
Results First Posted: December 19, 2020
Last Update Posted: December 19, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents