Phase 1
Completed N=170
PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma
Source: ClinicalTrials.gov NCT01621490 ↗Enrolled (actual)
170
Serious AEs
53.5%
Results posted
Dec 2019
Primary outcomePrimary: Median Change From Baseline to Week 7, of Interferon (IFN) and Interferon Gamma (IFN-gamma) Inducible Factors — 0.0130; 0.0320; 0.2310; 0.1600 pg/mL
Summary
The purpose of this study is to evaluate pharmacodynamic changes of Nivolumab and Nivolumab in combination with Ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Median Change From Baseline to Week 7, of Interferon (IFN) and Interferon Gamma (IFN-gamma) Inducible Factors |
0.0130; 0.0320; 0.2310; 0.1600; 0.0520; 0.0950 | — |
| PRIMARY Tumor Infiltrating Lymphocytes (TILs) as Measured by Medians in Percent Positive CD8 and Positive CD4 at Baseline and On-treatment Biopsy, Both Using the Mosaic Singleplex IHC Assay |
3.730; 7.230; 3.260; 11.105; 4.700; 5.615 | — |
| SECONDARY Frequency of Adverse Events or Death |
26; 25; 11; 14; 4; 2 | — |
| SECONDARY Frequency of AEs Leading to Discontinuation of Study Drug and SAEs |
20; 22; 20; 14; 2; 7 | — |
| SECONDARY Number of Laboratory Abnormalities in Specific Liver Tests |
2; 4; 8; 5; 0; 3 | — |
| SECONDARY Number of Laboratory Abnormalities in Specific Thyroid Tests |
9; 16; 7; 7; 1; 3 | — |
| SECONDARY Objective Response Rate (ORR) |
31.7; 22.7; 44.4; 40.0; 27.3; 70.0 | — |
| SECONDARY Median Duration of Response (mDOR) |
16.59; NA; NA; 26.25; NA; NA | — |
| SECONDARY Median Time to Response (mTTR) |
1.87; 2.78; 1.41; 2.51; 1.41; 1.71 | — |
| SECONDARY Progression Free Survival (PFS) |
3.68; 5.62; 7.00; 9.69; 4.93; NA | — |
| SECONDARY Immunogenicity of Nivolumab and Nivolumab in Combination With Ipilimumab as Measured by the Number of Serum Anti-drug Antibody (ADA) Positive Participants and the Number of Neutralizing ADA Positive Participants |
2; 5; 10; 1; 16; 4 | — |
| SECONDARY Objective Response Rate (ORR) by PD-L1 Expression |
40.0; 35.3; 85.7; 50.0; 50.0; 63.6 | — |
| SECONDARY Duration of Response (DOR) by PD-L1 Expression |
15.21; NA; NA; NA; NA; 26.25 | — |
| SECONDARY Progression Free Survival (PFS) by PD-L1 Expression |
4.50; 9.66; NA; NA; NA; 29.01 | — |
| SECONDARY Overall Survival Rate (OSR) |
92.7; 90.8; 85.2; 100.0; 90.0; 90.0 | — |
| SECONDARY Percent Probability for Progression Free Survival Rate (PFSR) |
53.7; 59.1; 54.6; 69.3; 54.5; 77.8 | — |
Eligibility Criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Part 1:
Inclusion Criteria
- Men and women >18 years
- Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
- Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
- Subject must have histologic or cytologic confirmation of advanced melanoma
- Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
Exclusion Criteria
- Active or progressing brain metastases
- Other concomitant malignancies (with some exceptions per protocol)
- Active or history of autoimmune disease
- Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)
- History of any hepatitis
- Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy
Part 2, 3 and 4:
Inclusion Criteria
- Men and women >16 years
- Eastern Cooperative Oncology Group (ECOG) status = 0 to 1
- Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma
- Subjects must never received anti-CTLA4 therapy
- Subjects must have histologic or cytologic confirmation of advanced melanoma
- Subjects must have at least two measurable lesions at baseline by CT or MRI as per RECIST 1.1 criteria
- Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies
- Subjects in Part 4 must have brain metastases
Exclusion Criteria
- Active or progressing brain metastases (except for Part 4 subjects)
- Other concomitant malignancies (with some exceptions per protocol)
- Active or history of autoimmune disease
- Positive test for HIV 1&2 or known AIDS
- History of any hepatitis
- Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies
Data sourced from ClinicalTrials.gov (NCT01621490). 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.