PIN in Combination With Sintilimab in Previously Treated pMMR/MSS CRC With Hepatic Metastases
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorChinese PLA General Hospital
About this trial
In this single-center,open-label, phase I study, the safety and efficacy of PIN in combination with anti-programmed cell death -1 (anti-PD1) antibody therapeutic regimen (sintilimab) will be evaluated in patients with advanced proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) with hepatic metastases . A total of 25 to 30 patients are planned to be enrolled and receive PIN plus sintilimab 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18-75 (inclusive).
Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Estimated life expectancy of more than 3 months.
Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic CRC with hepatic metastases have failed at least two lines of prior treatment.
Tumor tissues were identified as pMMR by immunohistochemistry (IHC) method or MSS by polymerase chain reaction (PCR).
Disqualifiers
Participants with DNA mismatch repair-deficient or microsatellite instability-high (dMMR /MSI-H) CRC.
Advanced CRC without hepatic metastases.
Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
Active central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to enrollment that are clinically stable and do not require intervention), or prior history of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 drug-related Central Nervous System (CNS) toxicity.
Trial design
Design model
Single group
Treatments tested in this trial
PIN+sintilimab
Biological/Vaccine1.Initial treatment phase: PIN injection frequency: day 0 and day 3, per 3 weeks for 8 cycles; PIN injection dosage: Cycle1: 4e9 or 8e9 viral particles based on the number of injectable lesions, their longest diameter, and the tumor volume capacity . Cycle 2\~8: 4e9 or 8e9 viral particles based on the tumor volume's capacity.Sintilimab: day -3, per 3 weeks for 8 cycles; 2.Maintenance treatment phase: No injection lesion: Sintilimab: 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.Sintilimab: 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.
Treatment groups
25 Participants
are divided into 1 treatment groupGroup A: PIN+sintilimabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.Secondary outcomes
1
DCR
DCR includes complete response (CR) ,partial response (PR) and stable disease (SD) defined by investigators according to Immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria or modified Response Evaluation Criteria in Solid Tumours (mRECIST) criteria.
Time frame
Up to 2 years since the initiation of treatment.2
ORR
ORR includes CR and PR defined by investigators according to iRECIST or mRECIST criteria.
Time frame
Up to 2 years since the initiation of treatment.3
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.4
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.Other outcomes
1
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 day 0 (before PIN injection), 3 (before PIN injection) and 6 during each treatment cycle ( each cycle is 21 days)2
The level of cytokines and anti-PIN antibodies 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 day 0 (before PIN injection), 3 (before PIN injection) and 6 during each treatment cycle ( each cycle is 21 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Chinese PLA General Hospital
Lead sponsor
Changping Laboratory
Collaborator
Source ClinicalTrials.gov
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