A Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors

Study Description

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Brief Summary:

This study will evaluate the safety profile, tolerability, PK, PD, and preliminary efficacy of BMS-813160 alone or in combination with either chemotherapy or nivolumab in participants with metastatic colorectal and pancreatic cancers.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Pancreatic Cancer	Drug: BMS-813160; Biological: Nivolumab; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: 5-fluorouracil (5-FU); Drug: Leucovorin; Drug: Irinotecan	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	348 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 1b/2 Study of BMS-813160 in Combination With Chemotherapy or Nivolumab in Patients With Advanced Solid Tumors
Actual Study Start Date :	August 4, 2017
Estimated Primary Completion Date :	December 10, 2020
Estimated Study Completion Date :	December 20, 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Combination Therapy 1; BMS-813160 with 5-fluorouracil (5-FU), leucovorin containing regimens in combination with irinotecan	Drug: BMS-813160; specified dose on specified days; Drug: 5-fluorouracil (5-FU); chemotherapy regimen; Drug: Leucovorin; chemotherapy regimen; Drug: Irinotecan; chemotherapy regimen
Experimental: Combination Therapy 2; BMS-813160, nab/paclitaxel and gemcitabine	Drug: BMS-813160; specified dose on specified days; Drug: Nab-paclitaxel; chemotherapy regimen; Drug: Gemcitabine; chemotherapy regimen
Experimental: Combination Therapy 3; BMS-813160 and Nivolumab	Drug: BMS-813160; specified dose on specified days; Biological: Nivolumab; specified dose on specified days; Other Names: Opdivo; BMS-936558
Experimental: Combination Therapy 4; BMS-813160, nab/paclitaxel + gemcitabine, and Nivolumab	Drug: BMS-813160; specified dose on specified days
Experimental: Combination Therapy 5; 5-fluorouracil (5-FU), leucovorin containing regimens in combination with irinotecan	Drug: 5-fluorouracil (5-FU); chemotherapy regimen; Drug: Leucovorin; chemotherapy regimen; Drug: Irinotecan; chemotherapy regimen
Experimental: Combination Therapy 6; Nab/paclitaxel and gemcitabine	Drug: Nab-paclitaxel; chemotherapy regimen; Drug: Gemcitabine; chemotherapy regimen
Experimental: Monotherapy; BMS-813160	Drug: BMS-813160; specified dose on specified days

Outcome Measures

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Primary Outcome Measures :

1. Adverse events (AEs) [ Time Frame: Approximately 4 years ]
   Measured by incidence of AEs
2. Serious adverse events (SAEs) [ Time Frame: Approximately 4 years ]
   Measured by incidence of SAEs
3. AEs meeting protocol-defined dose limiting toxicity criteria [ Time Frame: Approximately 6 months ]
   Measured by incidence of AEs that meet the protocol-defined dose limiting toxicity criteria
4. AEs leading to discontinuation [ Time Frame: Approximately 4 years ]
   Measured by incidence of AEs leading to discontinuation
5. Death [ Time Frame: Approximately 4 years ]
   Measured by incidence of deaths
6. Incidence of laboratory abnormalities [ Time Frame: Approximately 4 years ]
   Measured by any laboratory test result that is clinically significant or meets the definition of an SAE, any laboratory test result abnormality that required the patient to have study treatment discontinued or interrupted, or any laboratory test result abnormality that required the participant to receive specific corrective therapy
7. Electrocardiogram (ECG) [ Time Frame: Approximately 4 years ]
   ECGs will be evaluated by the investigator for any clinically significant changes or for changes meeting dose modifying criteria.
8. Summary measures of vital signs [ Time Frame: Approximately 4 years ]
   Including weight, body temperature, respiratory rate, pulse oximetry, seated blood pressure and heart rate.
9. Overall response rate (ORR) [ Time Frame: Approximately 2 years ]
   Part 2 Only: ORR is defined as the proportion of all treated participants whose Best overall response (BOR) is either complete response or partial response. BOR for a participant will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator.
10. Median duration of response (DOR) [ Time Frame: Approximately 2 years ]
    Part 2 Only: 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 or death, whichever occurs first.
11. Progression free survival (PFS) rate [ Time Frame: At 24 weeks ]
    Part 2 Only: 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.
12. Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples [ Time Frame: Approximately 4 years ]
    Part 1 Only: Examination of tumor-associated immune cells and microenvironment, through proteomics.

Secondary Outcome Measures :

1. Maximum observed plasma concentration (Cmax) [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
2. Time of maximum observed plasma concentration (Tmax) [ Time Frame: Approximately 4 years ]
   Summary statistics: medians and ranges
3. Trough observed plasma concentration (Ctrough) [ Time Frame: Approximately 4 years ]
   Summary statistics to assess attainment of steady state: geometric means and coefficients of variation; plots vs time by dose
4. Observed plasma concentration at 24 hours post dose (C24) [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
5. Area under the concentration-time curve from time 0 to 8 hours postdose [AUC(0-8)] [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
6. Area under the concentration-time curve from time 0 to 24 hours post dose [AUC(0-24)] [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
7. Apparent total body clearance (CLT/F) [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
8. Accumulation index, calculated based on ratio of AUC(0-24) and Cmax at steady state to after the first dose (AI) [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
9. Renal clearance (CLR) [ Time Frame: Approximately 4 years ]
   Summary statistics: geometric means and coefficients of variation
10. Percent urinary recovery over 24 hours corrected for molecular weight (%UR) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
11. Ratio of metabolite Cmax to parent Cmax, corrected for molecular (MR_Cmax) [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
12. Ratio of metabolite AUC(0-24) to parent AUC(0-24), corrected for molecular weight [MR_AUC(0-24)] [ Time Frame: Approximately 4 years ]
    Summary statistics: geometric means and coefficients of variation
13. Frequency of positive anti-drug antibody (ADA) to nivolumab during combination therapy [ Time Frame: Approximately 4 years ]
    Frequency distribution of baseline ADA-positive participants and ADA-positive participants after initiation of the treatment
14. Decrease in regulatory T cells (Treg) & tumor-associated macrophages (TAM) in tumor samples [ Time Frame: Approximately 4 years ]
    Part 2 Only: Examination of tumor-associated immune cells and microenvironment, through proteomics.
15. Overall response rate (ORR) [ Time Frame: Approximately 2 years ]
    Part 1 Only: ORR is defined as the proportion of all treated participants whose Best overall response (BOR) is either complete response or partial response. BOR for a participant will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator.
16. Median duration of response (DOR) [ Time Frame: Approximately 2 years ]
    Part 1 Only: 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 or death, whichever occurs first
17. Progression free survival (PFS) rate [ Time Frame: Approximately 2 years ]
    Part 1 Only: 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.

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:

• Participants must have metastatic colorectal or pancreatic cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Ability to swallow pills or capsules
• All participants will be required to undergo mandatory pre and on-treatment biopsies
• Adequate marrow function
• Adequate other organ functions
• Ability to comply with study visits, treatment, procedures, PK and PD sample collection, and required study follow-up

Exclusion Criteria:

• Histology other than adenocarcinoma (neuroendocrine or acinar cell)
• Suspected, known, or progressive CNS metastases (Imaging required only if participants are symptomatic)
• Participants with active, known or suspected autoimmune disease
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity
• Prior treatment with CCR2 and/or CCR5 inhibitors, PD-1, PD(L)-1 or CTLA-4 antibodies
• History of allergy to study treatments or any of its components of the study arm that participant is enrolling

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

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Contacts

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information.	please email:	Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT # and Site #.

  Show 33 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

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Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

Investigator Inquiry Form 

FDA Safety Alerts and Recalls 

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT03184870 History of Changes
Other Study ID Numbers:	CV202-103; 2017-001725-40 ( EudraCT Number )
First Posted:	June 14, 2017
Last Update Posted:	October 4, 2018
Last Verified:	October 2018

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

Additional relevant MeSH terms:

Colorectal Neoplasms; Pancreatic Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases	Paclitaxel; Irinotecan; Gemcitabine; Nivolumab; Albumin-Bound Paclitaxel; Fluorouracil; Antibodies, Monoclonal; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites