A Phase 1 interventional study of PIN +anti-PD1 in Solid Tumor and Adult, sponsored by Chinese PLA General Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-06-10.
Sponsored by Chinese PLA General Hospital · Phase 1, Interventional, and Treatment
In this single-center,open-label, phase I study, the safety and efficacy of PIN in combination with programmed cell death protein antibody (anti-PD1) therapeutic regimen will be evaluated in patients with late-stage advanced solid tumors . A total of 20 to 30 patients are planned to be enrolled and receive PIN plus anti-PD1 combined treatment. It aims to: 1).assess the safety and antitumor effects of the above combined treatment regimen. 2).detect the dynamic changes and molecular characteristics of PIN-induced CD8+ T cells with special phenotype in peripheral blood (PB) and transformation of tumor microenvironment (TME) after the treatment with PIN. 3).evaluate the immunological or clinical predictive biomarkers for toxicity and efficacy.
Several clinical studies have found that oncolytic viruses can provide clinical benefits to patients with different types, stages, and even advanced metastatic tumors. Especially when used in combination with immunotherapy, oncolytic viruses can sensitize tumor types that were initially unresponsive to immune checkpoint inhibitors.To date, there are hundreds of projects in clinical trial stages, especially in recent years, new generations of oncolytic viruses developed or in clinical stages have shown better safety and stronger anti-tumor capabilities. Through genetic engineering, oncolytic viruses can express target genes that have anti-tumor effects, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-12(IL-12),etc, further enhancing their anti-tumor effects. Despite these advances, how to obtain a more durable anti-tumor immune response and long-term benefits is still an urgent clinical issue.
Previous studies have confirmed that the Newcastle disease oncolytic virus (NDV) can selectively infect tumor cells while sparing normal cells, demonstrating an acceptable safety profile. In this study, investigators have developed a nove PIN . Preclinical studies have shown that combining PIN with anti-PD1 therapy can reverse the immunosuppressive microenvironment and transform "cold" tumors into "hot" tumors, thereby triggering local and systemic anti-tumor immune responses and significantly improving the efficacy of the immune checkpoint inhibitor(ICI). Based on these preclinical findings, investigators are conducting this clinical trial to evaluate the safety and anti-tumor activity of the PIN and anti-PD1 combination therapy in vivo.
In this study, 20 to 30 subjects will be enrolled. The initial dose for the first cycle will be determined as 4e9 or 8e9 viral particles based on the number of injectable lesions, their longest diameter, and the tumor volume capacity. Following the first cycle of treatment, the subsequent dose and injection sites of PIN will be adjusted based on the permissible volume of the injected tumor mass, according to the following principles:
PIN injection frequency: day 0 and day 3, per 3 weeks for 8 cycles; unless unavailability of injection lesion, disease progression (PD) or serious intolerable adverse events (AEs).
PIN injection dosage:
a.For patients with a single injectable lesion with a maximum diameter of \<8 cm, the initial cycle's PIN dose is 4e9 viral particles. Subsequent cycles will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the lesion's capacity to accommodate the injection volume;
b. For patients with a single injectable lesion with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles. Subsequent cycles will maintain this dose of 8e9 viral particles based on the lesion's capacity to accommodate the injection volume.
a.For patients with two injectable lesions, injections will alternate between the two lesions after two cycles. The initial cycle's PIN dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity;
b.For patients with injectable lesions with a maximum diameter of ≥8 cm, the initial cycle's PIN dose is 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the lesion's capacity.
a.For patients with multiple injectable lesions (≥ 3), after 1-2 cycles of injections in each injectable lesion, injections are alternated between lesions. The initial injection dose for each lesion is determined by the size of the lesion;
b.For lesions \<3 cm, the initial cycle's dose is 4e9 viral particles, and the second cycle will maintain this dose of 4e9 or increase it to 8e9 viral particles based on the tumor volume's capacity;
c.For lesions ≥3 cm, the initial cycle's injection dose is selected as 8e9 viral particles, and subsequent cycles will maintain this dose of 8e9 or decrease it to 4e9 viral particles based on the tumor volume's capacity.
Anti-PD1 infusion frequency: day -3, per 3 weeks for 8 cycles; until unacceptable toxicity occurred or PD.
Objectives:
The primary objective are to assess the safety and adverse event profile of the combination regimen.
The coprimary objective is immue response, assessed by CD8+T cells with special phenotype by Fluorescence Activating Cell Sorter (FACS).
The secondary objectives are to evaluate disease control rate (DCR), objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and quality of life.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's planned enrollment of 25 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Chinese PLA General Hospital is the lead sponsor of 558 studies on the registry; 202 are open to participants now.
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Adequate organ function as defined by the following criteria:
Exclusion Criteria:
1. Initial treatment phase: The combined treatment of PIN and anti-PD1 will be administered for 8 cycles; Unless PD or serious intolerable AEs. 2. Maintenance treatment phase: For patients who completed 8 cycles treatment and obtained effective disease control, if residual tumor lesions are still accessible for local injection, combination therapy will be continued. If no injectable lesion, anti-PD1 will be administrated per 3 weeks till 2 years unless PD or serious intolerable AEs. 3. Salvage treatment phase: For patients who experience disease recurrence or progression 16 weeks after ceasing PIN injection, if there are accessible lesions available for PIN injection, combination therapy will be resumed. If specific T cells induced by PIN can be detected in PB when there is no injectable lesion, then the specific T cells are amplified and transfused for salvage therapy.
Biological: PIN +anti-PD1
1. Initial treatment phase: PIN injection frequency: day0 and day 3, per 3 weeks for 8 cycles; PIN injection dosage: Cycle1: 4e9 or 8e9 viral particles of PIN based on the number of injectable lesions, their longest diameter, and the tumor volume capacity . Cycle 2\~8: 4e9 or 8e9 viral particles of PIN based on the tumor volume's capacity. Anti-PD1: day -3, per 3 weeks for 8 cycles; 2. Maintenance treatment phase: No injection lesion: Anti-PD1: day 1, per 3 weeks till 2 years unless PD or serious intolerable AEs. Have injection lesion: PIN: 4e9 or 8e9 viral particles based on the tumor volume's capacity, per 6 weeks (within first 24 weeks), then per 8 weeks till 2 years unless unavailability of injection lesion, PD or serious intolerable AEs. Anti-PD1: day 1, per 3 weeks till 2 years unless PD or serious intolerable AEs. 3. Salvage treatment phase: Dosage and frequency of administration refer to the initial treatment phase and maintenance treatment phase.
Incidence of treatment-related AEs
Treatment-related AEs are defined as any adverse medical events occurring since the initiation of treatment and grading these toxicities by Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
Time frame: Up to 12 months since the initiation of treatment.
DCR
DCR includes complete response (CR) ,partial response (PR) and stable disease (SD) defined by investigators according to investigators Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1), Immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria or modified Response Evaluation Criteria in Solid Tumours (mRECIST) (for hepatocellular carcinoma) criteria.
Time frame: Up to 2 years since the initiation of treatment.
ORR
ORR includes CR and PR defined by investigators according to RECIST 1.1, iRECIST or mRECIST(for hepatocellular carcinoma) criteria.
Time frame: Up to 2 years since the initiation of treatment.
DOR
DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators, or death regardless of cause.
Time frame: Up to 5 years since the initiation of treatment.
PFS
PFS is defined as the time from the initiation of treatment to the date of PD assessed by investigators, or death any cause. Participants not meeting the criteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.
Time frame: Up to 5 years since the initiation of treatment.
OS
OS is defined as the time from the initiation of treatment to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
Time frame: Up to 5 years since the initiation of treatment.
Quality of Life Assessment
Quality of life will be evaluated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30)，a core scale for all cancer patients, with a total of 30 items. Among them, items 29 and 30 are divided into seven levels. Based on the responses of the subjects, they are scored from 1 to 7 points. Other items are divided into four levels: never, a little, quite a bit, and a lot. When scoring, directly assign a score from 1 to 4 points.The researchers will assess changes in quality of life by calculating total scores.
Time frame: Every 6 weeks up to 2 years since the initiation of treatment.
Immunological response
Dynamics and molecular characteristics of CD8+ T cells with special phenotypes induced by PIN injection and its association with the treatment outcome. The relationship between the number of the CD8+ T cells and its anti-tumor effect was analyzed. To analyze the number and function of the CD8+ T cells in PB of patients with primary or acquired resistance after PIN injection and to summarize the key cellular and molecular mechanisms of resistance.
Time frame: PB samples are collected at least on days 0 (before PIN injection), 2, 3 (before PIN injection) and 5 during each treatment cycle ( (each cycle is 21 days)).
The level of cytokines in serum
The cytokines mainly include interleukin-1beta (IL-1β ) (pg / ml), IL-2(U/ml), IL-6(pg / ml),IL-10(pg / ml), tumor necrosis factor-α (TNF-α)(pg / ml), et al.
Time frame: PB samples are collected at least on days 0 (before PIN injection), 2, 3 (before PIN injection) and 5 during each treatment cycle ( (each cycle is 21 days)).
Plan to share: No
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