A Phase 0 Master Protocol Utilizing a Novel Intratumoral Microdosing Approach for Simultaneously Evaluating Multiple Drugs and Drug Combinations in Patients with Solid Tumors

• Published in: International journal of radiation oncology, biology, physics Vol. 112; no. 5; p. e48
• Main Authors: Ow, T.J., Mehta, V., Gersten, A.J., Newman, J.G., Maki, R.G., Gundle, K.R., Clayburgh, D.R., Li, R.J., Porosnicu, M., Nathan, C.A.O., Hatton, B.A., Sottero, K.H.W., Kung, G., Grenley, M.O., Anderson, K., Klinghoffer, R.A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2022
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2021.12.111

Tumor responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumor cells, and a heterogeneous tumor microenvironment (TME). All preclinical models fall short in capturing this complexity. CIVO (Comparative In Vivo Oncology) is an intratumoral microdose injection research tool intended to bridge the translational gap between preclinical and clinical studies by enabling in situ assessment of up to 8 oncology drugs or drug combinations simultaneously within a patient's tumor. The CIVO Phase 0 model was established under FDA's exploratory IND guidelines for microdosing. A Master Protocol was then developed, enabling ongoing evaluation of multiple investigational drugs and combinations without a need for stand-alone new protocols. Each investigational drug or combination is specified as a substudy of the Master Protocol, thus reducing administrative burden to clinical site staff and creating an infrastructure to ensure quality data and oversight of patient safety. This is a multi-center, open-label Phase 0 Master Protocol designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the TME when administered intratumorally in microdose quantities via the CIVO device. The safety of intratumoral microdose administration via the CIVO device will also be evaluated. Approximately 12 subjects are expected to be enrolled per substudy. All substudies will evaluate subjects ≥18 years with a diagnosis of solid tumors with scheduled surgical intervention. Eligible subjects have at least one lesion (primary or recurrent tumor or effaced metastatic lymph node) ≥2 cm in the shortest diameter that is surface accessible for CIVO injection. Each substudy will define the tumor type and specific eligibility criteria for enrollment. The study visits consist of screening, CIVO injection, surgical intervention, and two follow-up visits. All patients will be injected by the CIVO device containing microdose quantities of drugs specified in respective substudies. The CIVO device can be configured with 3, 5, or 8 needles and the device configuration will be assigned on a per-patient basis, dependent upon lesion size. Following surgical resection, the injected portion of the tumor will undergo central PD biomarker analysis. At the time of submission, the study is open for enrollment with 2 active substudies enrolling Head and Neck Squamous Cell Carcinoma (HNSCC) patients and 1 substudy enrolling HNSCC or soft tissue sarcoma patients. The Master Protocol was established to efficiently add substudies and accommodate evaluation of a wider repertoire of new agents in order to continually inform and de-risk drug development via the CIVO platform. Clinical trial information: NCT04541108. TBD TBD