Phase 1
Completed N=22
A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)
Carcinoma, Hepatocellular
Source: ClinicalTrials.gov NCT03289533 ↗
Enrolled (actual)
22
Serious AEs
36.4%
Results posted
Sep 2020
Primary outcomePrimary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03 — 2; 3; 16; 1 Participants
Summary
To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03 |
2; 3; 16; 1; 0 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03 |
13; 3; 5; 11; 2; 1 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03 |
15; 2; 1; 11; 2; 3 | — |
| SECONDARY Time to Disease Progression (TTP) |
5.52 | — |
| SECONDARY Progression Free Survival (PFS) |
5.52 | — |
| SECONDARY Percentage of Participants With Objective Response (OR) |
13.6 | — |
| SECONDARY Percentage of Participants With Disease Control (DC) |
68.2 | — |
| SECONDARY Time to Tumor Response (TTR) |
1.91 | — |
| SECONDARY Duration of Response (DR) |
7.29 | — |
| SECONDARY Overall Survival (OS) |
14.05 | — |
| SECONDARY Maximum Observed Serum Concentration of Avelumab |
231.06; 228.48; 245.66 | — |
| SECONDARY Maximum Observed Plasma Concentration of Axitinib |
89.70; 109.00 | — |
| SECONDARY Pre-dose Serum Concentration of Avelumab |
33.80; 19.419; 19.220; 23.922; 24.814; 29.832 | — |
| SECONDARY Pre-dose Plasma Concentration of Axitinib |
11.6439; 9.2226 | — |
| SECONDARY Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status |
17; 3 | — |
| SECONDARY Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells |
2.12; 0.91; 1.02 | — |
| SECONDARY Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells |
53.88 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs) |
3; 3 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of locally advanced or metastatic HCC, obtained by histology/cytology (on a prior tumor biopsy) or by imaging with serum α-fetoprotein (AFP) ≥400 ng/mL.
- All patients must provide at least 1 archival tumor specimen. If archival tumor specimen is no longer available, de novo tumor biopsy will be required during screening.
- HCC not amenable to local therapy.
- Measurable disease according to RECIST v. 1.1.
- Child Pugh Class A disease.
- BCLC stage B or C disease.
- No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart.
- ECOG performance status 0 or 1.
- Adequate bone marrow function, renal and liver functions
- Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
Exclusion Criteria
- Prior systemic treatment for advanced HCC, including prior treatment with approved or investigational drugs.
- Any prior locoregional therapy within 4 weeks and radiotherapy or surgical procedure within 2 weeks (4 weeks for major surgery) of enrollment.
- Patients with known symptomatic brain metastases requiring steroids.
- Presence of hepatic encephalopathy (ie, Child Pugh score of 2 or 3) and/or clinically relevant ascites (ie, Child Pugh score of 3).
- Presence of main portal vein invasion by HCC.
- Any of the following within the 12 months prior to enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular accident, transient ischemic attack.
- Active infection requiring systemic therapy except for hepatitis C virus (HCV) and hepatitis B virus (HBV).
Data sourced from ClinicalTrials.gov (NCT03289533). 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.