Topline: In the Phase 1 INDP-D101 study of Decoy20, a single urothelial cancer patient with liver metastases achieved a partial response on monotherapy but progressed by the following scheduled scan and discontinued. In the initial combination safety cohort with the PD-1 inhibitor tislelizumab, seven patients have been dosed. Among the first three evaluable patients, one achieved stable disease at the initial evaluation, and two had disease progression. Early safety in combination is being described as consistent with the profiles of the individual agents.
Indaptus has completed the monotherapy portion of INDP-D101 and moved into combination dosing with tislelizumab. The program is built around Decoy20, an intravenously administered, killed Gram-negative bacterial construct designed to deliver a multi-agonist innate immune stimulus, aiming to convert cold tumors into inflamed, PD-1–responsive microenvironments. Alongside the clinical update, the company disclosed a $5.7 million gross financing via convertible notes that were converted to equity in July, and guided to initial combination readouts later this year.
Strategically, the pivot from monotherapy to a PD-1 combination underscores the core hypothesis of this class: broad innate activation can resensitize or deepen responses to checkpoint inhibition, particularly in PD-1–experienced solid tumors where single-agent durability is elusive. The isolated partial response on monotherapy, followed by rapid progression, highlights both the biologic signal and its fragility in the absence of an adaptive checkpoint partner. Initiating early safety runs with a PD-1 inhibitor is the standard playbook for innate agonists and pattern-recognition receptor activators, with the gating factor being whether the cytokine and infusion reaction profile is manageable enough to enable repeated outpatient dosing and adherence to imaging schedules.
For sites, the operational footprint will hinge on infusion logistics, pre-medication, and monitoring for cytokine-related adverse events, as well as tight RECIST-driven assessments. If safety remains consistent, sites can treat on standard PD-1 clinic infrastructure; if not, inpatient observation or extended chair time will impede throughput. CROs will need robust central imaging and near-real-time safety data capture, given the novelty of the construct and the potential for transient activity between scans. For sponsors and CMC teams, reproducible manufacture of a killed bacterial product with stable immunostimulatory potency is a nontrivial hurdle that can become rate-limiting for expansion cohorts. Regulators will look for clarity on dose optimization, cytokine kinetics, hepatic lab trends—particularly relevant in patients with liver metastases—and whether any PD-1 re-challenge effect is emerging in previously treated populations. Vendors supporting biomarker work should anticipate demand for cytokine panels, innate/adaptive activation signatures, and TME “hotting” readouts that can de-risk subsequent cohort selection.
The financing update matters: $5.7 million converted to equity extends the runway but suggests continued dependency on capital markets or partnerships to sustain expansion beyond an initial safety cohort. That dynamic will influence the pace of site activation, geographic spread, and the ability to rapidly pivot toward the tumor types that show the earliest combinatorial traction.
Near term, watch for the first tranche of combination efficacy data: objective response rate in PD-1–experienced patients, durability beyond the initial evaluation, and the incidence of grade ≥3 AEs, infusion reactions, and treatment discontinuations. Dose refinement, cohort expansion criteria, and any move to a basket design will signal conviction. The key risks are familiar: underpowered signals that do not translate into expansion, safety that narrows dosing latitude, and financing constraints that slow execution. If the combination can demonstrate durable disease control with operationally tolerable safety, Decoy20 could progress to focused expansion cohorts in urothelial cancer or other PD-1–sensitive settings; absent that, the program will need sharper indication triage or additional combinations to justify continued investment.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
