Key points are not available for this paper at this time.
Eftilagimod alpha (E) is an MHC class II agonist that enhances anti-tumor immunity by mediating antigen presenting cell and CD8 T cell activation. AIPAC-003 (NCT05747794) is a randomized phase II/III trial testing E plus paclitaxel (P) in MBC patients (pts). An initial safety lead in (SLI) to test a higher 90 mg E dose (previous trials used 30 mg E) preceded the ongoing open-label, randomized dose optimization lead-in (phase II) component to determine the optimal biological dose (OBD) of E, to be potentially followed by a placebo-controlled phase III. Results from the SLI are reported here. Pts with HR+ and HER2-negative or HER2-low MBC resistant to endocrine-based therapy (ET) or mTNBC not eligible to PD-(L)1-based therapy could be enrolled. Pts received P (80 mg/m2 IV on D1, 8 and 15) followed by E (90 mg SC on D1 and 15) in a 4-week cycle up to 12 months. Imaging was done Q8W and assessed by the investigator per RECIST 1.1. Predefined DLTs were to be observed in the 1st cycle and assessed by an IDMC. Primary objective of the SLI was to determine if 90 mg E is safe. Further objectives included pharmacodynamic activity and efficacy. Six (6) pts were enrolled in a staggered approach May – Nov 2023 in the SLI. All pts were HR+, previously treated with ET including CDK4/6 inhibitors and considered ET-resistant. Pts had a median age of 66 years (range 35–78) and 83% had baseline ECOG 0. All completed the safety observation period without DLTs and 4 pts remain on study (exposure of 4+ months at data cut-off of January 15, 2024). No treatment emergent (TE) serious adverse events (AE), TEAEs leading to discontinuation, nor TEAEs ≥G3 were reported until cut-off. Disease control rate was 100%. 5 of 6 pts had tumor shrinkage; the confirmed ORR is 33%. Increase in Th1 biomarkers (IFN-gamma; CXCL10) and/or CD4/CD8 T cells was observed in all pts. 90 mg of E with weekly P in the first 6 pts is safe and is being evaluated further in the randomized OBD phase comparing 90 mg E to 30 mg E to determine optimal dosing.
Morales et al. (Wed,) studied this question.