This is an open-label, dose escalation (Phase I), and dose expansion (Phase IIA) study designed to evaluate safety and efficacy of IMSA101 alone or in combination with an ICI (Phase I and II). Therefore, the study will be conducted in 2 phases. The dose of IMSA101 in Phase IIA will be based on the monotherapy and combination Recommended Phase 2 Doses (RP2Ds) from Phase I.~The following methodology applies to all patients (unless otherwise indicated):~Pre-treatment screening radiographic tumor assessments will be collected within 30 days prior to initial dose for all patients. Photographic assessments for cutaneously-accessible lesions will be performed as detailed in a separate photography manual.~Treatment cycles will be 28 days in duration with lesions injected weekly on Day 1 for the first three weeks of Cycle 1 and then every 2 weeks during cycles 2 and beyond.~A single pre-defined lesion/lesion site (longest diameter ≥ 10 mm and ≤ 35 mm) shall be injected throughout study duration, if possible. Where the original injection site is considered by the investigator to become inaccessible, a second lesion/lesion site shall be selected as a replacement and this shall be used henceforth so long as it is considered accessible. Subsequent injection sites shall be replaced when they are considered inaccessible.~Where no remaining accessible lesions are present and where benefit of IMSA101 therapy is, in the opinion of the investigator, being derived by the patient, continued injections of IMSA101 into the vicinity of an inaccessible lesion or, in the case that a lesion can no longer be radiographically visualized, into the last known location of the non-visible lesion shall be allowed.~Patients will be admitted to the hospital for observation overnight following IT injection with IMSA101 on Day 1 of Cycle 1. Patients will be followed throughout the study for drug tolerability and safety by collection of clinical and laboratory data, including information on adverse events (AEs) using CTCAE v5.0 criteria, serious adverse events (SAEs), DLTs, concomitant medications, vital signs, and electrocardiograms (ECGs).~Patients will be assessed for anti-tumor efficacy based on radiographic assessments and if applicable, photographic tumor assessments, and analysis of Objective Response Rate (ORR), Time to Progression (TTP), and Progression Free Survival (PFS) using RECIST criteria (Appendix 13.2) at screening and the end (≤ 7 days) of even numbered cycles (Cycle 2, Cycle 4, etc.) after the first dosing.
Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor (ICI) (Phase I and II)