AIPAC-003: A randomized, double-blind, placebo-controlled phase 3 trial testing eftilagimod alpha (soluble LAG-3) in patients with HER2-neg/low metastatic breast cancer receiving paclitaxel, following an open-label dose optimization.

Abstract

TPS1125 Background: Eftilagimod alpha (efti), a soluble LAG-3 protein, acts as an MHC class II agonist that enhances immunity by mediating antigen presenting cell and CD8 T-cell activation. Data from a randomized, phase 2b trial of efti plus paclitaxel compared to placebo plus paclitaxel in patients (pts) with HR+ HER2– metastatic breast cancer (MBC) (AIPAC; NCT02614833) showed sustained pharmacodynamic activity that was linked to improved overall survival (OS) in the efti arm. AIPAC-003 is a randomized, double-blind, placebo-controlled phase 3 trial testing efti plus paclitaxel in HER2-neg/low MBC pts, following an initial open-label dose optimization lead-in (DOL) component to determine the optimal biological dose (OBD) of efti in this combination. Methods: The DOL phase will determine the OBD of efti prior to start of the P3 part of the study. Enrolment for the DOL began in November 2023 with the aim to recruit 66 pts. Primary objectives in the DOL are: safety and tolerability of 90 mg vs 30 mg efti and defining the OBD of efti in combination with weekly paclitaxel. Determination of the OBD will be based on the totality of safety and tolerability data together with overall response rate (ORR) and pharmacodynamic marker (CD8+ T cells, absolute lymphocyte count) data. Secondary objectives in the DOL include efficacy, QoL and PK profile always of 30 mg efti vs. 90 mg on top of weekly paclitaxel. In the Phase 3 component pts will be randomized to receive either paclitaxel + efti or paclitaxel + placebo in a double-blinded fashion. The primary endpoint (EP) for the proposed Phase 3 is OS and the exact patient population will be defined after determination of the OBD. Key secondary EPs include progression free survival and ORR by RECIST 1.1, quality of life and safety. Pts will receive paclitaxel (80 mg/m2 I.V. on D1, 8 and 15 in a 4-week cycle), followed by efti or placebo (DOL: 30 or 90 mg efti; Phase 3: OBD of efti or placebo) S.C. on D1 and 15 in a 4-week cycle for up to 12 months. Imaging is done every 8 weeks and assessed by the investigator. in the DOL blood samples are taken from 0 to 96 hours in cycle 1 and 4 to determine PK / PD profiles. PK / PD parameters are assessed by a central lab. Key inclusion criteria: Pts with either a) HR+ and HER2-neg/low and endocrine therapy-resistant MBC or b) TNBC not eligible for anti-PD-1-based therapy. Pts must have measurable disease, ECOG PS 0-1 and no prior chemotherapy for metastatic disease. Key exclusion criteria: Pts if HR+ who are not considered endocrine resistant and/or have received < 1 line of therapy in the metastatic setting. Pts who are considered TNBC and are eligible for anti-PD-(L)1 containing therapy. Clinical trial information: NCT05747794 .