Dose-escalation, tolerability, and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E) against chemotherapy-resistant malignant pleural mesothelioma: a clinical trial

Our plain-English summary of Dose-escalation, tolerability, and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E) against chemotherapy-resistant malignant pleural mesothelioma: a clinical trial, by K. Sakura, M. Kuroyama, Y. Shintani, et al (Cancer Immunology, Immunotherapy, 2024).

The study

• Authors: K. Sakura, M. Kuroyama, Y. Shintani, S. Funaki, S. Atagi, Y. Kadota, K. Kuribayashi, T. Kijima, T. Nakano, T. Nakajima, M. Sasai, M. Okumura, Y. Kaneda
• Journal: Cancer Immunology, Immunotherapy
• Published: 2024;73(12):243
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345).

© 2024. The Author(s).

In plain English

This was a single-arm, open-label, single-center phase I/II trial at Osaka University Hospital, Japan, from 2015 to 2017. It tested HVJ-E, an inactivated Sendai virus particle, in six patients with epithelial malignant pleural mesothelioma that had progressed despite chemotherapy. Three received a low dose (30,000 mNAU) and three a high dose (60,000 mNAU). Doses were injected into the tumor, then under the skin of the chest wall, eight injections over two cycles. All six had redness at the injection site. The authors reported no deaths owing to adverse events, no discontinuations and no dose-limiting toxicity; one patient had a grade 3 rise in amylase. On CT, all three low-dose patients had progressive disease and all three high-dose patients stable disease: disease control rates of 0% and 100%. Change in target lesions on CT differed by dose (p less than 0.05). The authors concluded that HVJ-E could be given safely at both doses and that higher doses may have some inhibitory effect. They called for larger, controlled trials and noted the lack of a control group and small patient numbers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-arm, open-label, single-center phase I/II clinical trial with a 3 + 3 dose-escalation design (the abstract calls it a phase I study)
• Who was studied: Six patients with chemotherapy-resistant malignant pleural mesothelioma at Osaka University Hospital, Japan, 2015 to 2017. Three were in the low-dose group and three in the high-dose group. All six had epithelial histology and five were men. Of 8 patients screened for the low dose, 5 were excluded; of 7 screened for the high dose, 4 were excluded.
• Exposure: Treatment with HVJ-E (inactivated hemagglutinating virus of Japan envelope) at a low dose of 30,000 mNAU or a high dose of 60,000 mNAU. It was injected into the tumor on day 1 and under the skin of the chest wall on days 5, 8 and 12, for eight injections over two cycles. This is a treatment study; asbestos exposure is not studied.
• Main results:
  • On CT using modified RECIST criteria, all 3 low-dose patients had progressive disease and all 3 high-dose patients had stable disease, giving disease control rates of 0% and 100% respectively.
  • On PET using PERCIST criteria, all 6 patients in both dose groups had stable metabolic disease, a disease control rate of 100% (6/6).
  • Change from baseline in target lesions on CT showed a dose-dependent difference between the low- and high-dose groups (p less than 0.05).
  • Comparing injected lesions with non-injected lesions by PET (SUL-peak), there was no clear difference at the end of the study.
  • One month after the end of the study, with fewer patients imaged, injected and non-injected lesions showed 20.4% and 8.0% antitumor efficacy (average SUL-peak baseline change). This difference was not significant.
  • Two months after the end of the study, antitumor efficacy was seen in 34.7% of lesions with intratumoral injection and 20.4% of lesions without it. The authors described this as a trend favoring intratumoral injection.
  • Redness at the injection site was the most common adverse event and occurred in both groups (all 6 patients per Table 2).
  • Grade 3 or higher increased amylase occurred in 16.7% (1/6) of patients. The text also reports grade 3 anemia in the low-dose group.
  • The authors reported no serious adverse events, no deaths owing to adverse events, no discontinuations and no dose-limiting toxicity.
  • No spread of tumor to the skin from the intratumoral injections was detected during an observation period of at least 3 months.
  • Mean overall survival after definitive diagnosis was 44.9 months. The authors reported no dose dependence for survival.
• The authors' conclusion: The authors concluded that HVJ-E could be safely given to patients with chemotherapy-resistant malignant pleural mesothelioma at both doses, and that higher doses may have some inhibitory effect. They named 60,000 mNAU as the recommended dose and said larger, controlled clinical trials are warranted.
• Limitations the authors state:
  • It was a single-arm study focused on safety, with no concurrent control group.
  • It was a single-center trial with a small number of patients.
  • Patients had varied prior treatments (chemotherapy, with or without surgery, or biological agents).
  • Fewer patients were imaged at the follow-up time points after the end of the study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Pleural Mesothelioma, Clinical Trial, Modified RECIST (mRECIST).

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