AIPAC-003 (Active Immunotherapy and PAClitaxel): A Randomized, Double-blind, Placebo-controlled Phase III Trial Testing Eftilagimod Alpha (Soluble LAG-3) in HER2-neg/Low Metastatic Breast Cancer Patients Receiving Paclitaxel, Following an Open-label Dose Optimization

Drug: Experimental: open label lead-in (phase 2): eftilagimod alpha 30mg + paclitaxel eftilagimod alpha 30mg s.c. + 80mg/m^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned. Biological: eftilagimod alpha APC activator, MHC II agonist Drug: Paclitaxel paclitaxel will be given as standard of care (chemotherapy) Patients have been randomised 1:1 to receive either 30mg or 90mg dosing of eftilagimod alpha (efti”) in combination with paclitaxel. Experimental: open label lead-in (phase 2): eftilagimod alpha 90mg + paclitaxel eftilagimod alpha 90mg s.c. + 80mg/m^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned. Biological: eftilagimod alpha APC activator, MHC II agonist Drug: Paclitaxel paclitaxel will be given as standard of care (chemotherapy) Experimental: Phase 3: eftilagimod alpha + paclitaxel eftilagimod alpha s.c. (OBD) + 80mg/m^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned. Biological: eftilagimod alpha APC activator, MHC II agonist Drug: Paclitaxel paclitaxel will be given as standard of care (chemotherapy) Placebo Comparator: Phase 3: placebo + paclitaxel placebo s.c. + 80mg/m^2 paclitaxel i.v. (same-day administration): The trial consists of a chemo-immunotherapy (chemo-IO) phase followed by an immunotherapy (IO)-phase. The chemo-IO phase consists of a planned 6 cycles of 4 weeks (28 days each) that may be longer or shorter depending on chemo tolerance. The IO-phase is planned to follow the chemo-IO phase. A maximum of 13 cycles (approx. 12 months) of treatment is planned. Drug: Paclitaxel paclitaxel will be given as standard of care (chemotherapy) Other: placebo placebo matching eftilagimod alpha ASCO 2023: 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. Phase II: patients who will receive 30mg efti or 90mg efti ASCO 2024 pts will be randomized to receive either paclitaxel + efti or paclitaxel + placebo in a double-blinded fashion. ...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.