Combination therapy · Oncolytic virus + checkpoint inhibitor
Oncolytic virus + PD-1,
priming tumours for immunotherapy.
PD-1 inhibitors often work poorly in 'cold' tumours with few T cells. The idea behind combining them with H101 is that the virus inflames the tumour first. This page covers the early clinical data, the schedule used, and how much is still unknown.
Quick answer
Why combine an oncolytic virus with PD-1 immunotherapy?
Checkpoint inhibitors release the brakes on T cells, but they need T cells in the tumour to work. In patients treated with H101, researchers measured more CD8+ T cells and dendritic cells, and also a rise in PD-1/PD-L1, the brake that PD-1 drugs block. A 2024 ESMO Open pilot tested H101 + nivolumab in 18 patients with advanced liver cancer that had progressed on prior systemic therapy. The objective response rate was 11.1%, disease control 38.9% and median overall survival 15.04 months, with no grade 3–4 adverse events. That is early evidence of tolerability, not proof of benefit.
n = 18
H101 + nivolumab pilot
Refractory advanced HCC, open-label single-arm
Yi et al., ESMO Open 2024
11.1%
Objective response
2 partial responses; disease control 38.9%
Yi et al., ESMO Open 2024
15.04 mo
Median overall survival
Median PFS 2.69 months; 6-month survival 88.9%
Yi et al., ESMO Open 2024
0
Grade 3–4 events
Fever in all 18 (grade 1–2)
Yi et al., ESMO Open 2024
40% / 75%
Ascites response / control
Intraperitoneal H101, 40 patients, at 4 weeks
Zhang et al., Mol Ther Oncolytics 2022
ASCO 2024
TROJAN 021 Phase II
H101 + ICIs in liver-metastatic gastric cancer
Abstract 2635
Settings
Where H101 + immunotherapy has been studied.
Refractory advanced HCC
Intratumoral H101 plus nivolumab after failure of prior systemic therapy (Fudan University Shanghai Cancer Center).
n = 18 · ESMO Open 2024
Liver-metastatic gastric cancer
TROJAN 021: prospective multicentre Phase II of H101 + immune checkpoint inhibitors, presented at ASCO 2024 (Shanghai Tenth People's Hospital).
ASCO 2024 #2635
Malignant ascites
Intraperitoneal H101 with immune profiling (Fudan University Shanghai Cancer Center). The authors suggested it may suit combination with immunotherapy.
Mol Ther Oncolytics 2022
Biology
What H101 did to the immune environment
Zhang et al. (Mol Ther Oncolytics, 2022) retrospectively reviewed 40 patients with malignant ascites given intraperitoneal H101 at Fudan University Shanghai Cancer Center. Immune profiling was done on ascites samples from 6 of them at days 0, 7 and 14.
| Finding | What the authors reported |
|---|---|
| Tumour cells | Significant decrease in tumour-cell density at days 7 and 14 |
| CD8+ T cells | Significant increase in density; CD8+ effector-memory fraction up by day 14 |
| Dendritic cells | Increased after treatment |
| Tumour-specific immunity | Tumour-specific CD8+ T-cell activation on day 14 by IFN-γ ELISpot (1 patient) |
| PD-1 | Increased on day 7, notably on Treg and exhausted CD4+ T cells |
| PD-L1 | PD-L1+ myeloid cells increased in 3 of 4 responders |
The authors describe the PD-1/PD-L1 rise as acquired immune resistance, more evident in responders — a rationale for adding checkpoint inhibitors.
Protocol
The published H101 + nivolumab schedule
The ESMO Open 2024 pilot used viral 'pre-treatment' first, then combination therapy. One lesion per patient was chosen for injection, guided by ultrasound, with intrahepatic lesions larger than 2 cm preferred.
| Phase | Timing | Treatment |
|---|---|---|
| Oncolytic-virus pre-treatment | Days 1 and 3 | Intratumoral H101, 2 vials per lesion (5.0×10¹¹ vp / 0.5 mL per vial) |
| Combination | From day 8 | H101 every 2 or 4 weeks + nivolumab 240 mg every 2 weeks |
| Duration | Up to 12 months | Or until progression, intolerable toxicity, consent withdrawal or study end |
Source: Yi et al., ESMO Open 2024. For illustration only — any plan is set by the treating oncologist.
FAQ
Oncolytic virus + immunotherapy — answered.
- My PD-1 immunotherapy stopped working. Could an oncolytic virus help?
- Possibly, but the evidence is early. In the ESMO Open 2024 pilot (18 patients whose HCC had failed prior systemic therapy), 2 had partial responses and 5 had stable disease. The two partial responders lived more than 2.5 years. The authors suggested local H101 may help reverse checkpoint-inhibitor resistance, but with 18 patients and no control group this is a hypothesis, not proof.
- Which PD-1 inhibitor was used with H101?
- Nivolumab 240 mg every 2 weeks in the ESMO Open pilot. The TROJAN 021 Phase II study used immune checkpoint inhibitors more broadly. Your oncologist chooses the agent.
- What are the side effects of combining H101 with PD-1?
- In the 18-patient pilot, all adverse events were grade 1–2. Fever affected everyone, typically within 12 hours of injection and usually settling in 2–4 hours without treatment. Injection-site pain affected 33.3% and cancer pain 16.7%. Reduced appetite, fatigue, raised bilirubin, raised ALT/AST, raised TSH and low phosphate each affected 11.1%. Infection and liver haemorrhage each affected 5.6%.
- Can H101 treat malignant ascites?
- In a retrospective series of 40 patients at Fudan University Shanghai Cancer Center, intraperitoneal H101 gave an ascites response rate of 40% and an ascites control rate of 75% at 4 weeks. The main side effects were fever (27.5%) and abdominal pain (20%), with no grade III/IV events reported in the abstract. Each patient received a single cycle.
- Is this available as a clinical trial?
- Some H101 combinations are studied in clinical trials at Chinese centres, and others are used in clinical practice off-label. Trial eligibility is strict, and whether international patients can enrol varies. We can check what is open for your diagnosis.
Related guides
Oncolytic Virus Therapy (hub)
Overview: what it is, who it may suit, how it's used in China.
Read the guideOncorine (H101) drug profile
Approval, genetic construct, approved indication and milestones.
Read the guideHow oncolytic viruses work
Selective replication, tumour lysis and turning 'cold' tumours 'hot'.
Read the guideH101 + TACE for liver cancer
Evidence, guideline status and treatment protocol for HCC.
Read the guideSafety & side effects
Adverse-event rates from the Phase III trial and combination studies.
Read the guideClinical trials in China
How international patients access Chinese oncology trials.
Read the guideSources
References
- Yi L, Ning Z, Xu L, et al. The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study. ESMO Open. 2024;9(2):102239.
- Zhang Y, Qian L, Chen K, et al. Intraperitoneal oncolytic virotherapy for patients with malignant ascites: characterization of clinical efficacy and antitumor immune response. Mol Ther Oncolytics. 2022;25:31–42.
- ASCO 2024 Annual Meeting, J Clin Oncol 2024;42(16_suppl): abstract 2635 (Yuan M et al., TROJAN 021 — H101 + immune checkpoint inhibitors in liver-metastatic gastric cancer, Phase II); abstract 5536 (Zhang Q et al., intratumoral H101 in persistent/recurrent/metastatic gynecological cancer); abstract e16265 (Wang T et al., oncolytic virus + HAIC of mFOLFOX for intrahepatic mass-forming cholangiocarcinoma).
- Muscolini M, et al. Oncolytic immunotherapy: can't start a fire without a spark. Cytokine Growth Factor Rev. 2020;56:94–101.
Running out of options
on immunotherapy?
Send your imaging, pathology and full treatment history, including which immunotherapy you received and for how long. A partner oncologist will tell you in writing whether an H101 combination or a relevant trial is worth considering.
This page is for general education only and is not medical advice. Oncolytic virus therapy is not suitable for every patient or every cancer. In China, Oncorine (H101) is approved only for advanced nasopharyngeal carcinoma in combination with chemotherapy; other uses described here are supported by retrospective studies, small trials, conference abstracts or expert consensus rather than large randomised trials. Treatment decisions are made by the treating oncologist after reviewing your records. We are an independent patient-coordination service and are not affiliated with the manufacturer.