Phase 2
Completed N=337
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
CANCER,NOS
Source: ClinicalTrials.gov NCT01714739 ↗
Enrolled (actual)
337
Serious AEs
69.7%
Results posted
Feb 2023
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 — 4; 16; 15; 284 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) - Parts 1, 2 and 5 |
4; 16; 15; 284; 10 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) - Parts 1, 2 and 5 |
1; 8; 9; 205; 7 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Parts 1, 2 and 5 |
1; 1; 4; 49; 5 | — |
| PRIMARY The Number of Participant Deaths in the Study - Parts 1, 2 and 5 |
2; 7; 5; 219; 5 | — |
| PRIMARY Number of Participants With Clinical Laboratory Test Abnormalities - Parts 1, 2 and 5 |
0; 0; 0; 2; 0; 0 | — |
| PRIMARY Objective Response Rate (ORR) |
25.0; 37.5; 40.0; 14.6; 50.0; 0 | — |
| SECONDARY Disease Control Rate (DCR) - Part 3 |
50.0; 33.3 | — |
| SECONDARY Median Duration of Response (mDOR) - Parts 3 and 5 |
NA | — |
| SECONDARY Median Time to Response (mTTR) - Part 3 |
8.10 | — |
| SECONDARY The Number of Participants With >=50% or >=80% Tumor Reduction - Parts 3 and 5 |
1; 2; 0; 0; 1; 0 | — |
| SECONDARY Overall Survival (OS) - Part 3 |
NA; 0.3 | — |
| SECONDARY Progression Free Survival (PFS) - Part 3 |
NA; 1.6 | — |
| SECONDARY Progression Free Survival Rate (PFSR) at 6 Months - Part 3 |
50.0; 33.3 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) - Part 3 |
2; 3 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) - Part 3 |
2; 3 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part 3 |
0; 0 | — |
| SECONDARY The Number of Participant Deaths in the Study - Part 3 |
1; 3 | — |
| SECONDARY Number of Participants With Clinical Laboratory Test Abnormalities - Part 3 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADA) - Parts 1, 2 and 5 |
0; 2; 0; 21; 1; 1 | — |
| SECONDARY The Number of Participants With PD-L1 Status at Pretreatment - Parts 1, 2 and 5 |
2; 5; 9; 127; 1; 1 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) - Parts 1, 2 and 5 |
2223.10; 6509.35; 22250.96; 52034.18; 65333.91; 2277.39 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] - Parts 1, 2 and 5 |
360903.09; 734836.53; 4462883.03; 9647500.52; 8819119.61; 569516.79 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Parts 1, 2 and 5 |
366418.73; 1155363.50; 4462883.03; 11418017.10; 10843715.48; 569516.79 | — |
| SECONDARY Time of Maximum Observed Concentration (Tmax) - Parts 1, 2 and 5 |
1.13; 1.05; 1.07; 1.22; 1.03; 1.08 | — |
| SECONDARY Half-life (T-HALF) - Parts 1, 2 and 5 |
383.96; 273.89; 515.07; 281.31 | — |
| SECONDARY Clearance Per Time (CLT) - Parts 1, 2 and 5 |
0.01; 0.01; 0.01; 0.01 | — |
| SECONDARY Trough Observed Concentration (Cmin, Also Known as CTAU) - Parts 1, 2 and 5 |
87.62; 521.28; 2572.90; 6195.04; 5190.00; 358.55 | — |
| SECONDARY Area Under the Pasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time ([AUC(INF)] - Parts 1, 2 and 5 |
— | — |
| SECONDARY Apparent Volume of Distribution During Terminal Phase (Vz) - Parts 1, 2 and 5 |
— | — |
| SECONDARY End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Liri) |
2223.10; 6434.65; 22250.96; 45163.87; 65333.91; 2277.39 | — |
| SECONDARY Ctrough - Parts 1, 2 and 5 (Liri) |
192.29; 521.28; 2572.90; 6195.08; 5190.00; 327.50 | — |
| SECONDARY End of Infusion Concentration (Ceoi) - Parts 1, 2 and 5 (Nivo) |
63.16; 66.33; 66.16; 52.48; 44.75; 104.47 | — |
| SECONDARY Ctrough - Parts 1, 2 and 5 (Nivo) |
19.15; 20.14; 21.36; 15.81; 17.30; 55.67 | — |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
Other protocol defined inclusion/exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT01714739). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.