A Phase 1/2a Study in 3 Parts to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of MIV-818 in Patients With Liver Cancer Manifestations

Medivir18 sites in 4 countries53 target enrollmentSeptember 5, 2018

ConditionsHepatocellular Carcinoma Intrahepatic Cholangiocarcinoma Liver Metastases

InterventionsMIV-818 (fostroxacitabine bralpamide) + pembrolizumab MIV-818 (fostroxacitabine bralpamide) + lenvatinib

DrugsMIV-818 (fostroxacitabine bralpamide) + pembrolizumab MIV-818 (fostroxacitabine bralpamide) + lenvatinib

Overview

Phase: Phase 1
Intervention: MIV-818 (fostroxacitabine bralpamide) + pembrolizumab
Conditions: Hepatocellular Carcinoma
Sponsor: Medivir
Enrollment: 53
Locations: 18
Primary Endpoint: Incidence and Severity of Adverse Events (AEs)
Status: Completed
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multicentre dose escalation/expansion study to assess safety and tolerability of MIV 818 as either monotherapy or in combination with 1) lenvatinib, a tyrosine kinase inhibitor used as a standard of care for the treatment of HCC or 2) pembrolizumab, a PD-1 inhibitor. The monotherapy parts of the study will include patients with various solid tumours that have spread to the liver, or alternatively originating in the liver. Evaluations of MIV-818 in combination with lenvatinib or pembrolizumab will only include patients with HCC.

Detailed Description

This study will be conducted in three phases. The initial phase, 1a, will enroll up to 12 subjects and include a total of one dose escalation per patient. Once pre-defined criteria for starting phase 1b monotherapy has been met among the enrolled patients in phase 1a, the next phase of the study will be initiated. Phase 1b monotherapy will enroll up to 30 patients in a 3+3 design with interpatient dose escalations. All dose escalation decisions will be made by a safety review committee that will meet regularly during the study conduct. When the MTD has been established, the SRC will provide a RP2D for monotherapy. Phase 1b combination constitutes an interpatient dose escalation to identify the RP2D for MIV-818 when used in combination with 1) lenvatinib and 2) pembrolizumab therapy. This part of the study will enroll up to 36 patients in a 3+3 design with interpatient dose escalations. Safety review will be performed by the SRC to determine the RP2D of MIV 818 for use in combination with lenvatinib and pembrolizumab. The SRC may recommend that the selected dose of MIV-818 is further evaluated in up to 30 patients in the Phase 2a expansion part of the study.

Registry

clinicaltrials.gov

Start Date

September 5, 2018

End Date

June 16, 2025

Last Updated

10 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Medivir

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Must have progressed on or are intolerant of standard therapy with:
•Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
•Histologically or cytologically confirmed iCCA, or
•Liver metastases from colon, rectal, or gastric solid tumors with limited extrahepatic tumor burden (any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
•Phase 1b Monotherapy-specific Inclusion Criterion:
•Histologically or cytologically confirmed HCC, including fibrolamellar HCC; patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and the medical monitor, or
•Histologically or cytologically confirmed iCCA, or
•Liver metastases from solid tumors, with limited extrahepatic tumor burden (i.e. no brain or bone metastases), any extrahepatic metastases should be limited to 1 other site and a maximum of 1 target lesion outside the liver).
•Combination therapy-specific Inclusion Criterion:
•Must have histologically or cytologically confirmed HCC that is considered advanced or unresectable, i.e. not suitable for either surgery, radiofrequency ablation (RFA) or loco-regional therapies (patients with HCC that received their diagnosis according to the agreed international radiological guideline are also admissible upon agreement between the investigator and medical monitor). Patients with fibrolamellar HCC or a mixed HCC and iCCA will be excluded.

Exclusion Criteria

•Tumor volume exceeding 50% of liver.
•History of previous malignancy within the last 5 years except basal cell carcinoma or carcinoma in situ in solid organ.
•Known CNS or brain metastases, unless previously treated and stable for 3 months.
•Ongoing significant disease other than target disease as judged by the investigator to compromise the patients' ability to complete this study.
•History of solid organ transplant or bone marrow transplant.
•Receiving immunosuppressive therapy including oral corticosteroids.
•Active hepatitis B (eg, hepatitis B surface antigen \[HBsAg\] reactive) and patients with active hepatitis C (eg, hepatitis C RNA is \[qualitative\] detected).
•Positive human immunodeficiency virus (HIV) infection.
•Poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months.
•Symptomatic encephalopathy within 3 months prior to Screening and/or requirement for medication for encephalopathy.

Arms & Interventions

MIV-818 (fostroxacitabine bralpamide) + pembrolizumab

Phase 2a expansion cohort HCC

Intervention: MIV-818 (fostroxacitabine bralpamide) + pembrolizumab

MIV-818 (fostroxacitabine bralpamide) + lenvatinib

Phase 2a expansion cohort HCC

Intervention: MIV-818 (fostroxacitabine bralpamide) + lenvatinib