Phase 1
Completed N=11
A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer
Source: ClinicalTrials.gov NCT02133742 ↗Enrolled (actual)
11
Serious AEs
55.8%
Results posted
Jun 2019
Primary outcomePrimary: Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase — 3 Participants
Summary
Despite substantial improvements of patients outcome in advanced RCC, durable and complete response is uncommon. The majority of patients eventually develop resistance and exhibit disease progression. Combining a PD-1 inhibitor, which has shown single-agent efficacy with axitinib may provide additional clinical benefit compared to axitinib alone.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLT): Dose Finding Phase |
3 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
52; 29 | — |
| SECONDARY Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) |
52; 23 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) According to Severity of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03 |
38; 1 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Hematology |
2; 1; 5; 1; 1; 3 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities: Urinalysis |
0; 11; 9; 25 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
— | — |
| SECONDARY Number of Participants With Eastern Cooperative Oncology Group [ECOG] Performance Status Score |
39; 10; 0; 0; 0; 3 | — |
| SECONDARY Objective Response Rate |
73.1 | — |
| SECONDARY Duration of Response (DR) |
18.6 | — |
| SECONDARY Time to Response (TTR) |
2.8 | — |
| SECONDARY Progression-Free Survival (PFS) |
20.9 | — |
| SECONDARY Overall Survival (OS) |
NA | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Axitinib |
46.58; 36.57; 24.83; 22.65 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib |
2.00; 3.00; 2.00; 2.00 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC 0-12) of Axitinib |
199.1; 219.4; 92.99; 116.9 | — |
| SECONDARY Apparent Oral Clearance (CL/F) of Axitinib |
25.11; 22.79; 53.77; 42.79 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Axitinib |
85.12; 50.91; 245.8; 225.5 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibodies (ADA) of Pembrolizumab (MK-3475) |
3 | — |
| SECONDARY Number of Participants With Programmed Death-Ligand 1 (PD-L1) Tumor Proportion Score |
9; 34; 1 | — |
| SECONDARY Number of Participants With Vascular Endothelial Growth Factor A (VEGF-A) Tumor Proportion Score |
— | — |
| SECONDARY Concentration of Vascular Endothelial Growth Factor A (VEGF-A) in Serum |
315.2; 432.1; 383.6 | — |
| SECONDARY Concentration of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in Serum |
4.11; 3.07; 3.69 | — |
| SECONDARY Concentration of Interleukin 8 (IL-8) in Serum |
NA; NA; NA | — |
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected
- At least one measureable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
- Eastern Cooperative Oncology Group performance status 0 or 1
- Controlled hypertension
Exclusion Criteria
- Prior treatment with systemic therapy for advanced RCC
- Prior adjuvant or neoadjuvant therapy if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
- Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
- Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
- Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of randomization except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low grade prostate cancer with no plans for treatment intervention
- In past 12 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
- In past 6 months: deep vein thrombosis or pulmonary embolism
Data sourced from ClinicalTrials.gov (NCT02133742). 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.