Oncolytic Virotherapy Plus PD-1 Inhibitor And Lenvatinib For Patients With Advanced Pancreatic Cancer

Study Overview

Oncolytic Virotherapy Plus PD-1 Inhibitor and Lenvatinib for Patients With Advanced Pancreatic Cancer

The objective of this study is to evaluate the safety/tolerability efficacy of oncolytic virotherapy combined with Tislelizumab plus lenvatinib for advanced pancreatic cancer patients who were relapsed or refractory to standard therapy

Recent studies have suggested that local destruction of tumor tissue by oncolytic virus induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed increased ORR in many types of human cancers. Therefore, the objective of this study is to evaluate the safety and efficacy of oncolytic virotherapy combined with Tislelizumab plus lenvatinib for advanced pancreatic cancer patients who were relapsed or refractory to standard therapy.

Pancreatic Ductal Adenocarcinoma

DRUG: H101
DRUG: Tislelizumab
DRUG: lenvatinib

2201249-8

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-03-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-02-25
First Submitted that Met QC Criteria 2022-03-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-02-27
First Posted (ACTUAL) 2022-03-31	Results First Posted N/A	Last Verified 2025-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: H101 + Tislelizumab+ Lenvatinib (Dose escalation and cohort expansion) H101 administered by intratumoral injection in combination with Tislelizumab administered intravenously (IV), and Lenvatinib administered orally.	DRUG: H101 H101 intratumorally injection starts at day 0. DRUG: Tislelizumab Tislelizumab plus lenvatinib will be initiated on day 1. Tislelizumab will be administered at 200 mg i.v. every 3 weeks orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdraw DRUG: lenvatinib lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: H101 + Tislelizumab+ Lenvatinib

(Dose escalation and cohort expansion) H101 administered by intratumoral injection in combination with Tislelizumab administered intravenously (IV), and Lenvatinib administered orally.

DRUG: H101

H101 intratumorally injection starts at day 0.

DRUG: Tislelizumab

Tislelizumab plus lenvatinib will be initiated on day 1. Tislelizumab will be administered at 200 mg i.v. every 3 weeks orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdraw

DRUG: lenvatinib

lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Primary Outcome Measures	Measure Description	Time Frame
Dose Limiting Toxicities (DLT)	The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.	28 days
Maximum tolerated dose	A MTD is determined if any cohort experiences 2 subjects with DLT's.	28 days
Adverse event (AE)		max 24 months

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response Rate	ORR according to RECIST 1.1	max 24 months
Duration of Response		max 24 months
Progression Free Survival		max 24 months
Overall survival		max 42 months
disease control rate		max 24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Written informed consent obtained.
Age ≥ 18 years at time of study entry.
Participants must have unresectable or metastatic histologically or cytologically confirmed pancreatic ductal adenocarcinoma.
Participants had relapsed or been refractory to standard therapy.
Participants had been unsuitable or unwilling to standard therapy
At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
Performance status (PS) ≤ 2 (ECOG scale).
Life expectancy of at least 12 weeks.
Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
Prior treatment with oncolytic virotherapy.
Radiotherapy administered less then 4 weeks prior to study treatment start.
Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:

Medication that is known to interfere with any of the agents applied in the trial.
Any other efficacious cancer treatment except protocol specified treatment at study start.
Patient has received any other investigational product within 28 days of study entry.
Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Peng Wang, MD, Fudan University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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