Background: Heavily pretreated late-stage breast cancer patients of any subtype represent a huge treatment challenge. Cisplatin may work in selected patients but is often disqualified because of toxicity. LiPlaCis is a liposomal formulation of cisplatin in development utilizing the sPLA₂-triggered targeted release of cisplatin. The prediction of cisplatin efficacy with a 205 mRNA profile has previously been demonstrated in a retrospective study in two NSCLC cancer patient cohorts receiving adjuvant cisplatin¹. Methods: The dose-escalation part of a phase 1/2 study, of 20 patients with a variety of locally advanced or metastatic solid tumors, suggested a phase 2 dose of LiPlaCis to be 75mg on day 1 and 8 q 3 wks. In this phase 2 part, the cisplatin drug response predictor (DRP) was used to select metastatic breast cancer (mBC) patients with response likelihood scores from FFPE diagnostic or later biopsies. Patients were treated until progression or unacceptable toxicity. Halfway through phase 2 part, the dosing was changed to a per body surface schedule (40 mg/m²) after a fatal event with the flat dosing (in effect 51 mg/m² for this patient). Among the 52 patients included in the phase 2 part, we here report data from the 37 patients with mBC platinum naïve, with DRP scores 34-100%, and with RECIST-defined response outcomes. Within this subgroup, we conducted a post hoc analysis of possible DRP cut-off values that could identify patients with a clinically meaningful response to treatment. Results: mBC patients had received a median of 7 previous treatment lines. A DRP score ≥80% (DRP80+) discriminated well between responders and non-responders to liposomal cisplatin. All 4 partial remissions in the study were in the DRP80+ group, and other key efficacy endpoints were in favor of the DRP80+ vs the lower scores (DRP80-). LiPlaCis was generally well tolerated, with a mean of 4.4 treatment cycles administered per patient. Only 1 SAE (pyelonephritis) was reported and considered related to treatment. One patient died whilst on treatment, but due to disease progression. From a total of 164 treatment cycles, 18 of the patients reported 1 grade 4 and 41 grade 3 AEs considered possibly related to treatment. Conclusions: LiPlaCis shows efficacy in heavily pretreated mBC patients, especially when using the DRP method as a companion diagnostic. Further, this is the first clinical study to prospectively validate DRP as a method to identify responders to chemotherapy cisplatin. 1) Buhl et al PLOS One doi: 10.1371/journal.pone0194609. Clinical trial information: NCT01861496.

²DRP80+ vs DRP80-.