Abstract 200P
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
EUCT 2022-003323-17; NCT05747794.
Legal entity responsible for the study
Immutep S.A.
Funding
This study issponsoredbyImmutep S.A.
Disclosure
F. Forget: Other, Travel, Accommodations, Expenses: Ipsen; Teva. E. Segui Solis: Financial Interests, Personal, Invited Speaker: Novartis, Veracyte, Pfizer, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Pfizer, Seagen; Financial Interests, Personal, Full or part-time Employment: SOLTI; Financial Interests, Personal, Research Grant: Amgen. J. Canon: Financial Interests, Institutional, Research Grant: Roche. P. Chalasani: Other, Consulting or Advisory Role: Lilly; Puma Biotechnology; OncoSec; Atossa Genetics; bioTheranostics; Gilead Sciences; Other, Research Funding: Pfizer; Lilly; Carrick Therapeutics; Phoenix Molecular Designs; Genentech/Roche; Ventana Medical Systems; BioAtla; Zentalis; Amgen; Radius Health. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Relay Therapeutics, Roche, Seagen, Cureo Science, iOne, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Pfizer, Roche, Seagen, AstraZeneca, Lilly, Medscape, AstraZeneca, AstraZeneca; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals, Pfizer; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Member of Board of Directors, Head: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. F. Vogl: Financial Interests, Personal, Other, Consultancy honoraria: Cellestia Biotech; Other, Institutional, Leadership Role: Immutep; Cellestia Biotech; Financial Interests, Personal, Stocks/Shares: Amgen; Cellestia Biotech. C. Mueller: Financial Interests, Personal, Other, Employment: Immutep; Financial Interests, Personal, Other, Stock: Immutep Ltd. F. Triebel: Financial Interests, Personal, Other, Employment: Immutep; Financial Interests, Personal, Other, Stock/Other: Immutep; Other, Personal, Other, Patents, Royalties, Other Intellectual Property: Being an inventor on patents on LAG-3 owned by Immutep SAS. All other authors have declared no conflicts of interest.