IMP321 (Eftilagimod Alpha) as Adjunctive to a Standard Chemotherapy Paclitaxel Metastatic Breast Carcinoma

AIPAC (Active Immunotherapy PAClitaxel): A Multicentre, Phase IIb, Randomised,Double Blind, Placebo-controlled Study in Hormone Receptor-positive Metastatic Breast Carcinoma Patients Receiving IMP321 (LAG-3Ig Fusion Protein) or Placebo as Adjunctive to a Standard Chemotherapy Treatment Regimen of Paclitaxel

The proposed Phase IIb clinical study aims to investigate the safety and efficacy of the active immunotherapy IMP321 in combination (adjunctive) with paclitaxel chemotherapy in patients with hormone receptor-positive metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma Breast Stage IV
• Intervention / Treatment: Biological: IMP321 (eftilagimod alpha); Drug: Paclitaxel; Drug: Placebo

Detailed Description

This is a multicentre, placebo-controlled, double-blind, 1:1 randomised Phase IIb study in female hormone receptor-positive metastatic breast cancer patients. The study comprises of two stages.

Stage 1 is the open-label, safety run-in stage consisting of cohort 1 and 2 to confirm the (RPTD) of IMP321 in combination with paclitaxel.

Stage 2 is placebo-controlled, double-blind randomisation stage, paclitaxel + IMP321 at the RPTD will be compared to paclitaxel + placebo.

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Burgge-Oostende
  • Brussel, Belgium, 1200
    • Cliniques universitaires Saint-Luc - Institut Roi Albert II - Cancérologie et Hématologie Oncologie clinique
  • Duffel, Belgium, 2570
    • Az Sint-Maarten
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen Breast and Gynecological Oncology Unit
  • Leuven, Belgium, 3000
    • UZ Leuven, campus Gasthuisberg Department of General Medical Oncology and Multidisciplinary Breast Centre
  • Namur, Belgium, 5000
    • Clinique Sainte-Elisabeth
  • Sint-Niklaas, Belgium, 9100
    • AZ Nikolass
  • Wilrijk, Belgium, 2610
    • GZA Ziekenhuizen campus Sint-Augustinus Oncologische Research
• France
  • Saint Priest en Jarez, France, 42271
    • Institut De Cancerologie De La Loire
  • Saint-Cloud, France, 92210
    • Institut Curie / Centre René Huguenin
  • Toulouse Cedex 9, France, 31059
    • Institut Claudius Regaud - IUC Toulouse - Oncopôle
• Germany
  • Essen, Germany, 45136
    • KEM- Brustzentrum der Kliniken Essen-Mitte
  • Frankfurt, Germany, 60389
    • Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus Centrum für Hämatologie und Onkologie
  • Heidelberg, Germany, 69120
    • NCT - Nationales Centrum für Tumorerkrankungen
  • Tübingen, Germany, 72076
    • UFKT - Universitäts-Frauenklinik Tübingen
  • Ulm, Germany, 89081
    • UFU - Universitätsfrauenklinik Ulm
• Hungary
  • Budapest, Hungary, 1032
    • Szent Margit Kórház Onkológiai Osztály
  • Budapest, Hungary, 1062
    • MH Egészségügyi Központ Onkológiai Osztály
• Netherlands
  • Amsterdam, Netherlands, 1081
    • VU University Medical Center
  • Geleen, Netherlands, 6162
    • Zuyderland MC
  • Groningen, Netherlands, 9700
    • UMCG Medisch Centrum Groningen
  • Leidschendam, Netherlands, 2262 BA
    • HMC Antoniushove
  • Maastricht, Netherlands, 6202
    • MUMC Medical Oncology department
  • Rotterdam, Netherlands, 3075
    • Erasmus MC
  • Venlo, Netherlands, 5912 BL
    • Viecuri Medisch Centrum
• Poland
  • Gdynia, Poland, 81 - 519
    • Kierownik Oddziału Onkologii i Radioterapii Szpital Morski im. PCK w Gdyni
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust The Christie Clinic - Medical Oncology
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals NHS Trust
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • St James' Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Able to give written informed consent and to comply with the protocol
2. Metastatic oestrogen receptor positive and/or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and/or metastasis
3. Female of age 18 years or above
4. Patients who are indicated to received first line chemotherapy with weekly paclitaxel
5. Evidence of measurable disease as defined by Response Evaluation Criteria version 1.1

6 Laboratory criteria: haematology and biochemistry results within the limits normally expected for the patient population.

Exclusion Criteria:

1. Prior chemotherapy for metastatic breast adenocarcinoma
2. Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy
3. Inflammatory carcinoma
4. Candidate for treatment with trastuzumab (or other Her2/neu targeted agents)
5. Systemic chemotherapy, radiation therapy or any other investigational agent within 4 weeks, endocrine therapy within 1 week prior to first dose of study treatment or CDK4/6 inhibitors within 5 times half-life (acc.to SPC) prior to first dose of study treatment and until completion of study treatment
6. Symptomatic known cerebral and/or leptomeningeal metastases
7. Serious intercurrent infection
8. Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment
9. Active acute or chronic infection
10. Active autoimmune disease requiring immunosuppressive therapy
11. Previous malignancies within the last three years other than breast carcinoma
12. Patients with prior organ or stem cell transplantation
13. Any condition requiring continuous systemic treatment with either corticosteroids or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paclitaxel + IMP321 at the RPTD; The chemo-immunotherapy phase consists of 6 cycles of 4 weeks. Patient will receive weekly paclitaxel at Days 1, 8 and 15 with adjunctive treatment of study agent, either IMP321, on Days 2 and 16 of each 4-week cycle. After completion of the 6-cycle chemo-immunotherapy phase, responding or stable patients will receive study agent (IMP321) every 4 weeks during the maintenance phase for an additional period of up to 12 injections	Biological: IMP321 (eftilagimod alpha); In the placebo-controlled, double-blind randomisation stage, paclitaxel + IMP321 at the RPTD will be compared to paclitaxel + placebo; Drug: Paclitaxel; Paclitaxel will be given in both treatment arms (classified as Non IMP)
Active Comparator: Comparator: Paclitaxel + Placebo; The chemo-immunotherapy phase consists of 6 cycles of 4 weeks. Patient will receive weekly paclitaxel at Days 1, 8 and 15 with adjunctive treatment of study agent, placebo, on Days 2 and 16 of each 4-week cycle. After completion of the 6-cycle chemo-immunotherapy phase, responding or stable patients will receive study agent (placebo) every 4 weeks during the maintenance phase for an additional period of up to 12 injections	Drug: Paclitaxel; Paclitaxel will be given in both treatment arms (classified as Non IMP); Drug: Placebo; In the placebo-controlled, double-blind randomisation stage, paclitaxel + placebo will be compared to paclitaxel + IMP321 at the RPTD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stage 1 to determine the recommended phase two dose for the randomised phase	Up to 12 months
Assessment of Progression-Free Survival (PFS)	Up to 37 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of the safety and tolerability of IMP321 as compared to placebo	Up to 19 months
Assessment of the overall survival (OS)	Up to 48 month
Stage 1: Evaluation of the pharmacokinetic e.g. Peak Plasma Concentration [Cmax]	Up to 12 months
Assessment of the change in quality of life (QOL)	Up to 37 months
Evaluation of the time to next treatment	Up to 37 months
Evaluation of objective response rate (ORR)	Up to 37 months
Evaluation of stable disease	Up to 37 months

Other Outcome Measures

Outcome Measure	Time Frame
Stage 1: assessment of Immuno-monitoring in a defined subset of 60 patients during the randomised stage	Up to 37 months

Collaborators and Investigators

• Sponsor: Immutep S.A.S.
• Investigators: Study Director: Immutep S.A.S, Immutep S.A.S.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 22, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 5, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Hormone receptor positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: IMP321 P011