Experts have gathered together a series of opinions to provide guidance to investigators, pharmaceutical companies, ethics committees, independent review boards, and regulatory agencies on conducting human intratumoral immunotherapy (HIT-IT) clinical research.1

The panel convened in March 2018 and included 11 experts from academia, 11 experts from the pharmaceutical industry, and 2 clinicians representing the European Society of Medical Oncology (ESMO). At the meeting, participants discussed intratumoral injection and delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of HIT-IT clinical trials. This harmonization would help to assure quality and “avoid a blurring of the data reported from different studies.”1 

A summary of the group’s conclusions included several recommendations related to HIT-IT trial design. Specifically, the panel recommended careful selection of patient populations that allow for clear detection of agent activity; systemic conduct of translational studies to better facilitate understanding of the mechanism of action of the HIT-IT; face-to-face meetings between interventional radiologists, radiologists, surgeons, and oncologists to define and prioritize radiological assessment of the injected site, as well as the use of image-guided injections.

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When communicating data on HIT-IT in metastatic cancers, reporting of objective response rate in injected and non-injected tumor lesions is essential for the proper evaluation of the efficacy of HIT-IT strategies, the panel wrote.

“HIT-IT is unique, as tumor responses in both injected and non-injected lesions could be of clinical relevance,” panel experts wrote. “It is therefore possible that dedicated tumor response criteria, specific for HIT-IT trials, will eventually outperform and replace the current iRECIST criteria.”

In addition, the number of injected and non-injected tumor lesions should be documented, and the median number of injected lesions per patient, anenestic responding tumor lesions per patient, and total lesions per patient should also be recorded, according to the researchers.

Evaluation of HIT-IT efficacy for localized cancer should involve the use of iRECIST overall response rate or disease control rate of injected tumor lesions, pathological complete response rate on surgical specimens, relapse-free survival for surgically removed local tumors, and progression-free survival for inoperable tumors.

The guideline also listed several practical challenges that remain related to HIT-IT, including variable injectability depending on the tumor type and site, systemic exposure to the injectable drug, the stability of the immunostimulatory agents when they are mixed together in combination, and more.

Disclosure: Support for the meeting was organized by ESMO and supported by funds from Aduro, Amgen Europe, Bioncotech, Eisai, Idera, Lytix, Merck US (MSD), Nektar, Pfizer, and Roche. For a full list of author disclosures, please refer to the original study.

Reference

  1. Marabelle A, Andtbacka R, Harrington K, et al. Starting the right in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT) [published online October 8, 2018]. Ann Oncol. doi: 10.1093/annonc/mdy423