Intratumoral injection of IP-001 following thermal ablation in patients with advanced solid tumors: A multicenter phase Ib/IIa trial with expansion cohorts in melanoma and soft tissue sarcoma patients (SAKK 66/17).

2610 Background: This trial combines the novel adjuvant immunomodulator IP-001, a glycan polymer, with laser ablation in patients with relapsed solid tumors. Methods: This is a non-randomized, open-label multicenter phase Ib/IIa trial with a dose-finding part 1 and a dose expansion part 2 in advanced melanoma and soft tissue sarcoma (STS). Primary objectives include the safety and tolerability of up to six 4-weekly cycles of intratumoral IP-001 following laser ablation (TRANBERG Thermal Therapy System, Clinical Laserthermia System AB), and 12-week disease control rate (12w-DCR) according to RECIST v1.1 in advanced melanoma. The dose-finding part used 4 mL of IP-001 (10 mg/mL). The activity endpoint for advanced melanoma used the 1 st stage of a Simon 2-stage design, with 12w-DCR ≤20% (H0) vs. ≥40% (H1) (type-I error 0.05, power 80%). Results: We treated 15 melanoma and 10 STS patients, including 4 in part 1 (n=28). Median age was 62 years, 57% were male, all patients had metastatic disease, including 60% with liver metastases. Most patients (78%) had received ≥3 prior lines of systemic treatment, including 79% with prior immunotherapy. Treatment was well tolerated with no dose-limiting toxicity, and a recommended IP-001 dose of 4 mL. Patients received a median of 2 (range 1 to 6) cycles of study treatment. Reasons for treatment discontinuation included physician’s decision (39%) and disease progression (25%). 27 patients (96%) experienced treatment-emergent adverse events (TEAE). IP-001-related TEAE occurred in 16 (57%) patients, including 5 (17%) patients with severe IP-001-related TEAE. Severe TEAE occurred in 20 (71%) patients overall. Most frequent mild IP-001-related TEAE included fever (36%), fatigue (21%), rash (14%), hypotension (11%), injection site reactions (11%) and flu-like symptoms (7%); 2 cases (7%) of severe allergic reactions were reported, including one serious reaction. Allergic reactions occurred at cycle 3 in both patients and resolved without sequelae. Treatment discontinuation for TEAE occurred in a single patient (4%). 12w-DCR in advanced melanoma was 21% (3/14 evaluable patients) (2-sided 90% CI: 6%, 46%), with stable disease in 50% and partial remission (PR) in one (7%) melanoma patient. 15 (53%) patients had radiological tumor shrinkage in ≥1 untreated tumor lesion. Median progression-free survival (PFS) in advanced melanoma was 3 months, with a 12-month PFS rate of 33%, indicating preliminary evidence of disease control beyond the 12-week primary endpoint window. Conclusions: Intratumoral IP 001 at a dose of 4 mL following thermal ablation is well tolerated, with mainly mild, transient immune-related events. Although the pre-specified activity endpoint was not met, the observed DCR and PFS support further evaluation of this novel immuno-oncologic strategy. Clinical trial information: NCT03993678 .