Phase 1
Completed N=104
A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma
Source: ClinicalTrials.gov NCT03006926 ↗Enrolled (actual)
104
Serious AEs
74.0%
Results posted
Dec 2020
Primary outcomePrimary: DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 6; 4 Participants
Summary
This is an open-label Phase 1b study designed to evaluate the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with hepatocellular carcinoma (HCC). The study will evaluate objective response rate and duration of response by modified Response Evaluation Criteria In Solid Tumors (mRECIST) for HCC and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
6; 4 | — |
| PRIMARY Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
97; 73 | — |
| PRIMARY DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs) |
— | — |
| PRIMARY DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST Version (v) 1.1 Assessed by Independent Imaging Review (IIR) |
38.0; 46.0 | — |
| PRIMARY DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR |
16.7 | — |
| PRIMARY DLT+Expansion Part: Duration of Response (DOR) Based on RECIST v1.1 Assessed by IIR |
NA | — |
| SECONDARY DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review |
43.0 | — |
| SECONDARY DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review |
17.1 | — |
| SECONDARY DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST v1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review |
9.6; 9.6; 9.3 | — |
| SECONDARY DLT+Expansion Part: Time-to-Progression (TTP) Based on mRECIST and RECIST v1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review |
9.9; 10.8; 9.8 | — |
| SECONDARY DLT+Expansion Part: Time-to-Response (TTR) Based on mRECIST Assessed by IIR |
2.5 | — |
| SECONDARY DLT+Expansion Part: Time-to-Response (TTR) Based on RECIST v1.1 Assessed by IIR |
2.8 | — |
| SECONDARY DLT+Expansion Part: Time-to-Response (TTR) Based on mRECIST Assessed by Investigator Review |
2.7 | — |
| SECONDARY DLT+Expansion Part: Overall Survival (OS) |
20.4 | — |
| SECONDARY DLT+Expansion Part, Cmax: Maximum Observed Plasma Concentration for Lenvatinib |
127; 98.3; 168; 145 | — |
| SECONDARY DLT+Expansion Part, Tmax: Time to Reach the Cmax for Lenvatinib |
3.90; 4.00; 3.92; 4.00 | — |
| SECONDARY DLT+Expansion Part, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib |
1230; 1690; 1950 | — |
| SECONDARY DLT+Expansion Part, AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib |
673; 868; 736; 793; 1020; 1120 | — |
| SECONDARY DLT+Expansion Part, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib |
1340; 1900; 1540; 4690; 2530 | — |
| SECONDARY DLT+Expansion Part, t1/2: Terminal Elimination Phase Half-Life for Lenvatinib |
7.71; 6.64; 5.75; 7.33; 6.48 | — |
| SECONDARY DLT+Expansion Part, CL/F: Apparent Total Clearance for Lenvatinib |
5.98; 6.32; 7.79 | — |
| SECONDARY DLT+Expansion Part, Vz/F: Apparent Terminal Volume of Distribution for Lenvatinib |
66.6; 60.6; 64.7 | — |
| SECONDARY DLT+Expansion Part, Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib |
154; 145; 201; 193 | — |
| SECONDARY DLT+Expansion Part, Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib |
42.9; 14.3; 33.4; 34.3 | — |
| SECONDARY DLT+Expansion Part, Tss,Max: Time to Maximum Observed Concentration at Steady State For Lenvatinib |
6.01; 4.02; 3.89; 4.00 | — |
| SECONDARY DLT+Expansion Part, AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib |
4150; 2330 | — |
| SECONDARY DLT+Expansion Part, Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib |
2.89; 5.14 | — |
| SECONDARY DLT+Expansion Part, Css,Av: Average Steady State Plasma Concentration for Lenvatinib |
173; 97.2 | — |
| SECONDARY DLT+Expansion Part, Vz,ss/F: Apparent Terminal Volume of Distribution at Steady State for Lenvatinib |
30.6; 48.5 | — |
| SECONDARY DLT+Expansion Part, Rac (Cmax): Accumulation Ratio of Cmax for Lenvatinib |
1.07; 1.48; 1.17; 1.38 | — |
| SECONDARY DLT+Expansion Part, Rac (AUC0-8 Hour): Accumulation Ratio of AUC(0-8 Hour) for Lenvatinib |
1.07; 1.32; 1.83 | — |
| SECONDARY DLT+Expansion Part, %PTF: Percent (%) Peak-trough Fluctuation for Lenvatinib |
161; 161 | — |
| SECONDARY DLT+Expansion Part, Ctrough: Trough (Pre-dose) Serum Concentration for Pembrolizumab |
0.00; 12.3; 21.9; 25.0; 26.6; 27.9 | — |
| SECONDARY DLT+Expansion Part: Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status |
3; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Confirmed diagnosis of hepatocellular carcinoma (HCC)
- HCC for which no other appropriate therapy is available. Note: Expansion Part: No prior systemic therapy for advanced/unresectable HCC
- Stage B (not applicable for transarterial chemoembolization [TACE]), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
- At least 1 measurable target lesion according to modified Response Evaluation Criteria in Solid Tumors (mRECIST)
- Child-Pugh score A
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
- Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal limits. (control by thyroid replacement therapy is acceptable.) Participants with T3, free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible
- Adequately controlled blood pressure
- Adequate renal function
- Adequate bone marrow function
- Adequate blood coagulation function
- Adequate liver function
- Males or females age ≥ 18 years at the time of informed consent
- Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
Exclusion Criteria
- Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months
- Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
- Active infection (any infection requiring systemic treatment). Hepatitis B or C [HBV/HCV] is allowed
- Participants with CNS metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
Data sourced from ClinicalTrials.gov (NCT03006926). 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.