A Phase 2 study in platinum-sensitive recurrent ovarian cancer reported a 50% objective response rate among 24 evaluable patients treated with intraperitoneal cisplatin plus intraperitoneal rintatolimod (Ampligen) and intravenous pembrolizumab, including 5 complete and seven partial responses. The regimen was administered in up to six 3‑week cycles to patients with measurable peritoneal disease. By contrast, pembrolizumab monotherapy in the Keynote‑100 trial produced ORRs of 7.4% and 9.9% in similar settings. Durability, PFS, OS, and safety outcomes were not disclosed in the abstract presented at SITC.
The core development is AIM ImmunoTech’s formal readout of a completed single‑arm, locoregional chemo‑immunotherapy study (NCT03734692), positioning Ampligen, a TLR3 agonist, as a potential immune‑priming adjunct to checkpoint blockade. The company also highlighted immunologic correlates suggesting increased T‑cell trafficking with the combination. It underscored a patent estate covering Ampligen’s use with anti‑PD (L)1 agents through 2039 in several jurisdictions. Operationally, the approach hinges on intraperitoneal delivery for both cisplatin and Ampligen, layered onto systemic PD‑1 inhibition.
Strategically, this is an expansion play to reframe a legacy innate immune modulator as a checkpoint potentiator, leaning on a strong headline ORR and the well‑known limitations of PD‑1 agents in ovarian cancer. The choice of a platinum‑sensitive population, however, introduces attribution risk: response rates are inherently higher with platinum rechallenge, and the three‑drug design obscures the incremental contribution of Ampligen. Historical comparisons to monotherapy PD‑1 are an intentionally low bar; the more relevant benchmark is contemporary platinum‑based doublets with or without bevacizumab, where randomized data and maintenance strategies now dominate practice. The intraperitoneal route is a differentiator intended to amplify local immunity within the peritoneal cavity, but it also narrows the addressable treatment setting and complicates scalability.
For sites, the regimen demands capabilities that have migrated to tertiary centers: intraperitoneal port placement, aseptic compounding and administration of IP agents, and coordinated management of cytotoxic and immune‑related adverse events. That will influence site selection, training, and monitoring, and it reduces the feasibility of any decentralized components. CROs should anticipate more intensive safety oversight and procedural variability across gynecologic oncology programs that have uneven experience with IP chemotherapy. Regulators are likely to focus on durability of response, the safety profile of concurrent IP cisplatin and PD‑1 inhibition, and a trial design that cleanly isolates Ampligen’s effect—most plausibly a randomized, controlled study testing IP cisplatin plus pembrolizumab with or without Ampligen. Payers will ultimately require evidence of incremental clinical benefit over standard platinum regimens and clarity on the total cost of care, given the procedural load.
Near term, the gating items are mature DOR, PFS, and safety data, alongside a definitive next‑step protocol. A factorial or add‑on randomized Phase 2 would be the most direct path to de‑risk contribution of components; a maintenance‑oriented strategy post‑platinum response could also be explored to disentangle cytotoxic effects from immune modulation. Biomarker work—PD‑L1 status, HRD/BRCA, tumor‑immune microenvironment metrics—will matter if AIM seeks to focus the signal and streamline enrollment. Manufacturing and CMC for sterile intraperitoneal formulation, plus reliable IP supply logistics, will be scrutinized before any scale‑up. Watch for whether AIM secures a development collaboration with a PD‑1 sponsor, how it addresses site network constraints for IP therapy, and whether regulators accept ORR as sufficient to progress or demand randomized evidence before advancing to pivotal plans.
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.
