Study in Metastatic Breast Cancer Patients Receiving Eftilagimod Alpha or Placebo in Combination With Paclitaxel Chemotherapy

Breast Carcinoma Clinical Trial

— AIPAC-003  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05747794
• Other study ID #: AIPAC-003
• Secondary ID: 2022-003323-17
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 22, 2023
• Est. completion date: July 31, 2027

Study information

• Verified date: May 2024
• Source: Immutep S.A.S.
• Contact: Chief Medical Officer
• Phone: +49 30 88716843
• Email: enquiries[@]immutep.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 849
• Est. completion date: July 31, 2027
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms

Intervention

Biological:
• eftilagimod alpha
APC activator, MHC II agonist

Drug:
• Paclitaxel
paclitaxel will be given as standard of care (chemotherapy)

Other:
• placebo
placebo matching eftilagimod alpha

Locations

Country	Name	City	State
Belgium	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
Spain	Institut Català d'Oncologia	Badalona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Parc Taulí Hospital Universitari	Barcelona
Spain	VHIO - Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario de Jaén	Jaén
Spain	Unidad Ensayos Clínicos Oncología Fundació IRB Lleida	Lleida
Spain	Hospital Universitario La Paz	Madrid
Spain	START Madrid - FJD, Hospital Fundación Jiménez Diaz	Madrid
United States	Oncology Consultants	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Carolina Blood and Cancer Care Associates	Rock Hill	South Carolina
United States	The George Washington University Cancer Center	Washington	District of Columbia
United States	The Oncology Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Immutep S.A.S.

Countries where clinical trial is conducted

United States,  Belgium,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of Overall survival (OS)		Until trial end, death, withdrawal of consent or lost to follow-up, assessed up to 60 months
Primary	Determination of the Optimal Biological Dose (OBD)		Up to 15 months
Primary	Frequency of adverse events (AEs)		Up to 15 months
Primary	Severity of adverse events (AEs)		Up to 15 months
Primary	Duration of adverse events (AEs)		Up to 15 months
Primary	Occurrence of dose-limiting toxicities (DLTs)		Up to 15 months
Primary	Occurrence of clinically relevant abnormalities in vital signs		Up to 15 months
Primary	Occurrence of clinically relevant abnormalities in physical examinations		Up to 15 months
Primary	Occurrence of clinically relevant abnormalities in 12-lead ECGs		Up to 15 months
Primary	Occurrence of clinically relevant abnormalities in safety laboratory assessments		Up to 15 months
Secondary	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
Secondary	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
Secondary	Changes from baseline in quality of life (QOL) as assessed by questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30	EORTC QLQ-C30 is a 30-item self-administered cancer specific questionnaire designed to measure QOL in the cancer population	Up to 13 months
Secondary	PK parameter: area under the curve (AUC) (dose optimization lead-in only)		Up to 4 months
Secondary	PK parameter: peak serum concentration (Cmax) (dose optimization lead-in only)		Up to 4 months
Secondary	PK parameter: time to reach Cmax (tmax) (dose optimization lead-in only)		Up to 4 months
Secondary	PK parameter: systemic clearance (CL) (dose optimization lead-in only)		Up to 4 months
Secondary	PK parameter: elimination half-life (t1/2) (dose optimization lead-in only)		Up to 4 months
Secondary	PK parameter: volume of distribution (VD) (dose optimization lead-in only)		Up to 4 months