Study in Metastatic Breast Cancer Patients Receiving Eftilagimod Alpha or Placebo in Combination with Paclitaxel Chemotherapy
- Conditions
- Breast Carcinoma
- Interventions
- Registration Number
- NCT05747794
- Lead Sponsor
- Immutep S.A.S.
- Brief Summary
The goal of this clinical trial is to compare the safety and efficacy of eftilagimod alpha (efti) in combination with paclitaxel standard of care chemotherapy in participants with metastatic breast cancer.
The main questions it aims to answer are:
* What is the optimal biological dose (OBD) of efti in combination with weekly paclitaxel chemotherapy?
* Can efti combined with weekly paclitaxel chemotherapy prolong overall survival in participants with metastatic breast cancer if compared to weekly paclitaxel chemotherapy alone?
In the first component of the trial (phase 2, lead-in) researchers will compare two groups (different dose levels of efti in combination with standard chemotherapy) to see if the treatment is safe and well tolerated and evaluate which is the optimal biological dose. In the second component of the trial (phase 3) researchers will assess if the treatment of metastatic breast cancer with the optimal biological dose of efti in combination with paclitaxel is superior compared to chemotherapy alone (placebo-controlled).
The treatment concept of each trial component consists of a chemo-immunotherapy phase followed by an immunotherapy phase. In the first phase participants will be treated with efti plus paclitaxel chemotherapy or placebo plus paclitaxel chemotherapy. After completion of the chemotherapy per standard of care, participants will be treated with the study agent alone.
- Detailed Description
The AIPAC-003 trial consists of an open-label dose optimization lead-in component followed by a double-blinded, randomized, placebo-controlled phase 3 component.
The main objectives of the dose optimization lead-in (phase 2) are to evaluate and compare the safety and tolerability of 2 different dose levels of efti (30 mg and 90 mg) combined with paclitaxel, and to define the optimal biological dose (OBD) of efti in combination with weekly paclitaxel for the phase 3 part of the trial. Recruitment to the dose-optimization lead-in will be considered complete when 29 participants per cohort are randomized and considered evaluable for OBD analysis.
The main objective of the phase 3 is to demonstrate that overall survival (OS) is superior in participants treated with efti combined with weekly paclitaxel compared to weekly paclitaxel plus placebo. Approximately 771 participants will be randomized 2:1 to Arm A (active arm): paclitaxel + efti at OBD and Arm B (control arm): paclitaxel + placebo. The exact patient population will be defined after determination of the OBD.
The duration of the trial will be approximately 24 months for the dose optimization lead-in component and 60 months for the phase 3 component. The phase 3 will start prior to the completion of the phase 2 (once the OBD has been defined).
It is planned to conduct the trial at up to 20 sites in up to 4 countries across North America and Europe for the lead-in and at up to 150 sites in up to 25 countries across North America, Europe, Latin America and the Asian Pacific region for the phase 3.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 849
- Metastatic HR+ positive (estrogen receptor positive and/or progesterone receptor positive) or hormone receptor negative (HR˗), and HER2-neg breast adenocarcinoma, histologically proven by biopsy on the last available tumor tissue
- Participants with HR+ metastatic breast cancer (MBC) who progressed on or after ≥1 line of endocrine based therapy and are indicated to receive chemotherapy for metastatic disease
- Participants with HR- MBC (i.e. triple-negative breast cancer [TNBC]) who are indicated to receive paclitaxel chemotherapy without PD 1/PD-L1 therapy in the 1st line setting for metastatic disease
- ECOG performance status 0-1
- Expected survival longer than three months
- Prior chemotherapy for metastatic breast adenocarcinoma
- Participants with HR+ MBC who have received <1 line of ET based therapy in the metastatic setting
- Participants with HR+ MBC who are not primary or secondary resistant to ET-based therapy and would be candidates to ET based therapy as per applicable treatment guidelines
- TNBC participants who are candidates for PD-1/PD-L1 therapy in combination with chemotherapy
- Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description open label lead-in (phase 2): eftilagimod alpha 30mg + paclitaxel eftilagimod alpha 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. open label lead-in (phase 2): eftilagimod alpha 30mg + paclitaxel 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. open label lead-in (phase 2): eftilagimod alpha 90mg + paclitaxel eftilagimod alpha 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. Phase 3: placebo + paclitaxel 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. Phase 3: placebo + paclitaxel placebo 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. Phase 3: eftilagimod alpha + paclitaxel eftilagimod alpha 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. open label lead-in (phase 2): eftilagimod alpha 90mg + paclitaxel 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. Phase 3: eftilagimod alpha + paclitaxel 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.
- Primary Outcome Measures
Name Time Method Frequency of adverse events (AEs) Up to 15 months Determination of Overall survival (OS) Until trial end, death, withdrawal of consent or lost to follow-up, assessed up to 60 months Severity of adverse events (AEs) Up to 15 months Duration of adverse events (AEs) Up to 15 months Occurrence of dose-limiting toxicities (DLTs) Up to 15 months Occurrence of clinically relevant abnormalities in vital signs Up to 15 months Determination of the Optimal Biological Dose (OBD) Up to 15 months Occurrence of clinically relevant abnormalities in physical examinations Up to 15 months Occurrence of clinically relevant abnormalities in 12-lead ECGs Up to 15 months Occurrence of clinically relevant abnormalities in safety laboratory assessments Up to 15 months
- Secondary Outcome Measures
Name Time Method PK parameter: systemic clearance (CL) (dose optimization lead-in only) Up to 4 months Determination of Progression Free Survival (PFS), based on RECIST, v1.1 Until occurrence of progressive disease, or the start of any further next line anticancer treatment, or until the end of the trial for any other reason, assessed up to 60 months PK parameter: volume of distribution (VD) (dose optimization lead-in only) Up to 4 months PK parameter: area under the curve (AUC) (dose optimization lead-in only) Up to 4 months PK parameter: peak serum concentration (Cmax) (dose optimization lead-in only) Up to 4 months Evaluation of Objective Response Rate (ORR) based on RECIST v1.1 Until occurrence of progressive disease, or the start of any further next line anticancer treatment, or until the end of the trial for any other reason, assessed up to 60 months Changes from baseline in quality of life (QOL) as assessed by questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 Up to 13 months EORTC QLQ-C30 is a 30-item self-administered cancer specific questionnaire designed to measure QOL in the cancer population
PK parameter: time to reach Cmax (tmax) (dose optimization lead-in only) Up to 4 months PK parameter: elimination half-life (t1/2) (dose optimization lead-in only) Up to 4 months
Trial Locations
- Locations (22)
The Oncology Institute
🇺🇸Whittier, California, United States
The George Washington University Cancer Center
🇺🇸Washington, D.C., District of Columbia, United States
Carolina Blood and Cancer Care Associates
🇺🇸Rock Hill, South Carolina, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
AZ Sint-Jan Brugge Oostende av
🇧🇪Brugge, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussel, Belgium
Grand Hopital de Charleroi - Hopital Notre Dame
🇧🇪Charleroi, Belgium
Universitair Ziekenhuizen Antwerpen
🇧🇪Edegem, Belgium
Centre Hospitalier de l'Ardenne
🇧🇪Libramont, Belgium
Clinique Saint-Pierre- Ottignies
🇧🇪Ottignies-Louvain-la-Neuve, Belgium
ARENSIA Exploratory Medicine LLC
🇬🇪Tbilisi, Georgia
ARENSIA Exploratory Medicine Phase I Unit
🇲🇩Chisinau, Moldova, Republic of
Institut Català d'Oncologia
🇪🇸Badalona, Spain
VHIO - Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Parc Taulí Hospital Universitari
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitario de Jaén
🇪🇸Jaén, Spain
Unidad Ensayos Clínicos Oncología Fundació IRB Lleida
🇪🇸Lleida, Spain
START Madrid - FJD, Hospital Fundación Jiménez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain