An investigator-initiated clinical study in patients with refractory or recurrent solid tumors: ‘R-ISV-FOLactis’ trial

Abstract

Aim: In situ vaccination, a kind of therapeutic cancer vaccine, can be realized by radiotherapy and intratumoral immune injection. This study combines intratumoral injection, radiotherapy and PD-1 blockade for synergistic antitumor effect. Materials & methods: Patients with advanced solid tumors who are unresponsive or intolerant to standard treatment will be treated with hypofractionated radiotherapy, intratumoral injection of FOLactis, PD-1 blockade. The primary end point is to observe the efficacy and safety, with the secondary end point to evaluate abscopal effects and the correlation between the immunological rationale and efficacy. Discussion: The combined regimen will be utilized to trigger antitumor immunity and is expected to be feasible and effective and provide a novel option for the comprehensive treatment of cancer.

Clinical Trial Registration: ChiCTR2200060660 (ChiCTR.gov.cn)

Article highlights

Background

• In situ vaccination refers to a method to reverse suppressive tumor microenvironment, stimulate tumor immunogenicity and tumor-specific T cells by radiotherapy or intratumoral injection. Radiotherapy can induce immunogenic cell death, while intratumoral injection promote the release of large number of antigens, enhancing the capacity of antigen-presenting cells to enhance antitumor immunity.

Patients & methods

• This exploratory clinical study is designed as an open-label, single-center trial aimed at treating patients with advanced solid tumors who are unresponsive or intolerant to standard treatment by combining radiotherapy, intratumoral injection and PD-1 blockade. The objective efficacy and safety of the combined regimen will be evaluated.

Discussion

• Radiotherapy alone does not induce a robust in situ vaccine effect in most cases. Studies have shown that radiotherapy can cause upregulation of programmed death-ligand 1 expression. As a result, the combination of radiation with PD-1 mAb may be a feasible strategy to enhance antitumor immunity. In this study, the combination of radiotherapy, intratumoral immune injection and intravenous PD-1 inhibitor will be utilized to treat patients with advanced solid tumors to augment antitumor immunity.

Conclusion

• Safety and efficacy of the combined regimen will be further confirmed.

Keywords: :

• Abscopal effect
• cancer-immunity cycle
• comprehensive therapy
• immune checkpoint inhibitors
• immunotherapy
• in situ vaccination
• intratumoral immune injection
• probiotics
• radiotherapy
• solid tumors

Author contributions

Conception and design: J Zhu, B Liu and R Li; Recruited patients: L Zhu, X Wang, J Shen and Q Liu.; Member of study management group: J Dai, J Bao, X Chen, J Zhu, Y Zhou, L Min, H Qi, M Tian and J Shen; Manuscript drafting and revision: J Dai and R Li.

Financial disclosure

The study was financially supported by the National Natural Science Foundation of China (82203178 and 82272852 [R Li]), the fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2022-LCYJ-MS-09), the fundings for the development of new technology from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (XJSFZJJ202025) and the key project foundation of Nanjing for the development of medical technology (ZKX20024). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The ethics committee of Drum Tower Hospital approved the study (approval number 2022-101-01). The trial is registrated on the ChiCTR. gov.cn (ChiCTR2200060660). The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The study was financially supported by the National Natural Science Foundation of China (82203178 and 82272852 [R Li]), the fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2022-LCYJ-MS-09), the fundings for the development of new technology from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (XJSFZJJ202025) and the key project foundation of Nanjing for the development of medical technology (ZKX20024).