Preliminary efficacy and safety of intratumoral long-acting cisplatin-SRGel (TumoCure) in refractory locally advanced head and neck squamous cell carcinoma: Phase Ib CLPR-001.

6051 Background: Refractory LA-HNSCC progressing despite standard therapies is associated substantial locoregional disease driven morbidity and limited effective salvage therapies that achieve modest response rates and are poorly tolerated. Intratumoral (IT) therapies enabling high and durable drug exposure at the site of disease with minimal systemic toxicity may address this unmet need. TumoCure is a long acting injectable IT cisplatin formulation (100mg/mL) incorporated in SRGel, a solvent free biodegradable matrix designed to provide IT cisplatin release for up to 2 months, aiming to maximize locoregional cisplatin exposure with minimal systemic exposure. Methods: CLPR-001 is an open-label, multicenter Phase I/Ib study evaluating IT TumoCure in patients with chemo and/or radio resistant LA-HNSCC with no available curative or effective standard treatment options. TumoCure is administered as a single IT injection; individualized based on tumor dimensions to optimize IT dispersion. The primary endpoint is safety and tolerability. Secondary endpoints include locoregional response by RECIST v1.1, PK and QoL assessment. Results: Eight patients received IT TumoCure (5 males and 3 females) with a mean age of 66y. Patients were in average 7y from diagnosis and were heavily pretreated: 7/8 (87.5%) had prior surgery and 7/8 (87.5%) were platinum-resistant or refractory. The mean number of prior systemic treatment lines (including RT and IO) was 3. Target lesions reflected substantial locoregional tumor burden (longest diameter 30-98 mm). Administration was feasible across tumor sizes, with injection volumes of 0.4-1.0 mL. Treatment was generally well tolerated. Procedure related AEs were uncommon and limited to injection site pain. No systemic cisplatin related AEs were reported. Early clinical activity was observed, with 3 months best response of 45% and 37% reductions in tumor diameter and corresponding volumetric reductions of 75% and 36% respectively. Patients also experienced clinically meaningful improvement in tumor bulk related manifestations. Preliminary PK analyses demonstrated systemic platinum exposure at least one order of magnitude lower than historical systemic cisplatin exposure. Conclusions: In heavily pretreated, platinum-resistant/refractory patients, TumoCure treatment was safe and well tolerated. Early signals of tumor regression and improvement in tumor bulk-related symptoms were observed, supported by markedly reduced systemic platinum exposure. These findings support continued development of TumoCure as treatment for refractory LA-HNSCC. A subsequent study is planned to evaluate TumoCure + IMRT in cisplatin ineligible patients, addressing an unmet need where current chemoradiation regimens remain suboptimal, with the goal of improving outcome while minimizing toxicity. Clinical trial information: NCT05200650 .