Clinical trial NCT05747794: Study in Metastatic Breast Cancer Patients Receiving Eftilagimod Alpha or Placebo in Combination with Paclitaxel Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Breast Carcinoma
Lead sponsor: Immutep S.A.S.
Sponsor class: INDUSTRY
First posted: 2023-02-28
Enrollment: 849
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial consists of an open-label dose optimization lead-in component (phase 2) followed by a double-blinded, randomized, placebo-controlled phase 3 component.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determination of Overall survival (OS)
timeFrame: Until trial end, death, withdrawal of consent or lost to follow-up, assessed up to 60 months
measure: Determination of the Optimal Biological Dose (OBD)
timeFrame: Up to 15 months
measure: Frequency of adverse events (AEs)
timeFrame: Up to 15 months
measure: Severity of adverse events (AEs)
timeFrame: Up to 15 months
measure: Duration of adverse events (AEs)
timeFrame: Up to 15 months
measure: Occurrence of dose-limiting toxicities (DLTs)
timeFrame: Up to 15 months
measure: Occurrence of clinically relevant abnormalities in vital signs
timeFrame: Up to 15 months
measure: Occurrence of clinically relevant abnormalities in physical examinations
timeFrame: Up to 15 months
measure: Occurrence of clinically relevant abnormalities in 12-lead ECGs
timeFrame: Up to 15 months
measure: Occurrence of clinically relevant abnormalities in safety laboratory assessments
timeFrame: Up to 15 months
Secondary outcomes:
measure: Determination of Progression Free Survival (PFS), based on RECIST, v1.1
timeFrame: 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
measure: Evaluation of Objective Response Rate (ORR) based on RECIST v1.1
timeFrame: 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
measure: Changes from baseline in quality of life (QOL) as assessed by questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30
timeFrame: Up to 13 months
measure: PK parameter: area under the curve (AUC) (dose optimization lead-in only)
timeFrame: Up to 4 months
measure: PK parameter: peak serum concentration (Cmax) (dose optimization lead-in only)
timeFrame: Up to 4 months
measure: PK parameter: time to reach Cmax (tmax) (dose optimization lead-in only)
timeFrame: Up to 4 months
measure: PK parameter: systemic clearance (CL) (dose optimization lead-in only)
timeFrame: Up to 4 months
measure: PK parameter: elimination half-life (t1/2) (dose optimization lead-in only)
timeFrame: Up to 4 months
measure: PK parameter: volume of distribution (VD) (dose optimization lead-in only)
timeFrame: Up to 4 months
Other outcomes:
Locations:
city: Whittier
country: United States
facility: The Oncology Institute
state: California
city: Washington, D.C.
country: United States
facility: The George Washington University Cancer Center
state: District of Columbia
city: Rock Hill
country: United States
facility: Carolina Blood and Cancer Care Associates
state: South Carolina
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge Oostende av
city: Brussel
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi - Hopital Notre Dame
city: Edegem
country: Belgium
facility: Universitair Ziekenhuizen Antwerpen
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Ottignies-Louvain-la-Neuve
country: Belgium
facility: Clinique Saint-Pierre- Ottignies
city: Tbilisi
country: Georgia
facility: ARENSIA Exploratory Medicine LLC
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Exploratory Medicine Phase I Unit
city: Badalona
country: Spain
facility: Institut Català d'Oncologia
city: Barcelona
country: Spain
facility: VHIO - Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Parc Taulí Hospital Universitari
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Jaén
country: Spain
facility: Hospital Universitario de Jaén
city: Lleida
country: Spain
facility: Unidad Ensayos Clínicos Oncología Fundació IRB Lleida
city: Madrid
country: Spain
facility: START Madrid - FJD, Hospital Fundación Jiménez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
References: