A Study of an Anti-KIR Antibody Lirilumab in Combination With an Anti-PD1 Antibody Nivolumab and Nivolumab Plus an Anti-CTLA-4 Ipilimumab Antibody in Patients With Advanced Solid Tumors

NCT01714739 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CA223-001
• Study Type: interventional
• Target: 337
• Locations: 6 countries
• Sites: 30

Brief Summary

To assess the safety and tolerability and preliminary anti-tumor activity of lirilumab (BMS-986015) given in combination with nivolumab (BMS-936558) and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination. In addition, to assess the combinations of lirilumab and nivolumab or lirilumab and nivolumab plus ipilimumab (BMS-734016) in subjects with advanced (metastatic and/or unresectable) refractory solid tumors.

Conditions

CANCER,NOS

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5

  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

  From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)

• Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5

  A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

  From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)

• Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5

  Number of participants that experienced an AE leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

  From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)

• The Number of Participant Deaths in the Study - Parts 1, 2 and 5

  The number of participants who died.

  From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)

• Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5

  Number of participants that experienced a clinical laboratory test abnormality, including hematology and serum chemistry, and thyroid panel abnormalities. Abnormalities considered are those Grade 3-4 events with a \>= 1 grade increase from baseline. Laboratory tests are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 3 is severe, and Grade 4 is life threatening. Baseline is defined as the last non-missing measurement prior to the first dosing date and time.

  From first dose to 150 days post last dose (up to an average of 51 weeks and a maximum of 2.5 years)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR for a participant was derived using investigator-provided tumor measurements per RECIST v1.1. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From first dose up to approximately 2.5 years

Secondary Outcomes (27)

• Disease Control Rate (DCR) - Part 3

  From first dose up to approximately 2.5 years

• Median Duration of Response (mDOR) - Parts 3 and 5

  From first dose to the date of the first documented tumor progression as determined or death due to any cause, whichever occurs first. (Up to approximately 2.5 years)

• Median Time to Response (mTTR) - Part 3

  From date of first dose of study medication to the date of the first documented objective response (up to approximately 2.5 years)

• The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5

  From first dose until progressive disease (PD) or treatment discontinuation, whichever occurs earlier. (Up to approximately 2.5 years)

• Overall Survival (OS) - Part 3

  From date of first dose of study medication to the date of death for any cause. (Up to approximately 2.5 years)

Study Arms (4)

Part 1

EXPERIMENTAL

Dose Escalation and Initial Signal Detection in Multiple Solid Tumors - Nivolumab with Lirilumab

Drug: Lirilumab; Drug: Nivolumab

Part 2 and 3: Cohort Expansion

EXPERIMENTAL

In platinum-refractory recurrent or metastatic SCCHN - Nivolumab with or without Lirilumab

Drug: Lirilumab; Drug: Nivolumab

Part 4: Cohort Expansion

EXPERIMENTAL

Additional Signal Detection in Solid Tumors - Nivolumab with Lirilumab (Study Part 4 Removed; No Subjects Enrolled)

Drug: Lirilumab; Drug: Nivolumab

Part 5 and 6

EXPERIMENTAL

Safety Lead-In and Additional Signal Detection in Solid Tumors -- Nivolumab Plus Ipilimumab with Lirilumab (Study Part 6 Removed; No Subjects Enrolled)

Drug: Lirilumab; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Lirilumab DRUG

Specified dose on specified days.

Also known as: BMS-986015, IPH-2102, ANTI-KIR (Killer-cell Immunoglobulin-like Receptors)

Part 1; Part 2 and 3: Cohort Expansion; Part 4: Cohort Expansion; Part 5 and 6

Nivolumab DRUG

Specified dose on specified days.

Also known as: BMS-936558, ANTI-PD1

Part 1; Part 2 and 3: Cohort Expansion; Part 4: Cohort Expansion; Part 5 and 6

Ipilimumab DRUG

Specified dose on specified days.

Also known as: BMS-734016, Anti-CTLA4

Part 5 and 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
• During cohort expansion, subjects with various solid tumors that have received at least one and no more than 5 prior treatment regimens
• Subjects must have measurable disease
• Subject must consent to provide previously collected tumor tissue
• Women and men ≥18 years of age with performance status of 0 or 1
• At least 4 weeks since any previous treatment for cancer

You may not qualify if:

• Active or chronic autoimmune diseases
• Uncontrolled or significant cardiovascular disease
• Chronic hepatitis (except for subjects with hepatocellular carcinoma)
• Active infection
• Active Central nervous system (CNS) metastases
• Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome((HIV/AIDS)
• Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (30)

Ucsf

San Francisco, California, 94115, United States

Location

Florida Cancer Affiliates - Ocala

Ocala, Florida, 34471, United States

Location

University Of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

Lutherville, Maryland, 21093, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Med Ctr

Portland, Oregon, 97213, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Eye and Ear Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Texas Oncology-Central Austin Cancer Center

Austin, Texas, 78731, United States

Location

University Of Texas Medical Branch Of Galveston

Galveston, Texas, 77555, United States

Location

University Of Washington

Seattle, Washington, 98195, United States

Location

Juravinski Cancer Center

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution

Bordeaux, 33075, France

Location

Local Institution

Lyon, 69373, France

Location

Local Institution

Nice, 06189, France

Location

Local Institution

Paris, 75005, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

IRCCS Istituto Nazionale Tumori Milano

Milan, MI, 20133, Italy

Location

Local Institution

Siena, 53100, Italy

Location

Local Institution

Barcelona, 08035, Spain

Location

Local Institution - 0038

Madrid, 28034, Spain

Location

Local Institution

Madrid, 28050, Spain

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Neoplasms

Interventions

lirilumab; Receptors, KIR; Nivolumab; spartalizumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Receptors, Natural Killer Cell; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

please email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: October 26, 2012
• Study Start: October 7, 2012
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: February 2, 2023
• Results First Posted: February 2, 2023

Record last verified: 2023-01

Locations

CA (2); IT (2); FR (5); ES (3); CH (2); US (16)