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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Adenocarcinoma Breast Stage IV

Intervention / Treatment
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* Biological: IMP321 (eftilagimod alpha)
* Drug: Placebo
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give written informed consent and to comply with the protocol Metastatic oestrogen receptor positive and/or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and/or metastasis Female of age 18 years or above Patients who are indicated to received first line chemotherapy with weekly paclitaxel 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: Prior chemotherapy for metastatic breast adenocarcinoma Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy Inflammatory carcinoma Candidate for treatment with trastuzumab (or other Her2/neu targeted agents) 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 Symptomatic known cerebral and/or leptomeningeal metastases Serious intercurrent infection Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment Active acute or chronic infection Active autoimmune disease requiring immunosuppressive therapy Previous malignancies within the last three years other than breast carcinoma Patients with prior organ or stem cell transplantation Any condition requiring continuous systemic treatment with either corticosteroids or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel + IMP321 at the RPTD<br>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)<br>* In the placebo-controlled, double-blind randomisation stage, paclitaxel + IMP321 at the RPTD will be compared to paclitaxel + placebo<br>Drug: Paclitaxel<br>* Paclitaxel will be given in both treatment arms (classified as Non IMP)<br>|
| Active Comparator: Comparator: Paclitaxel + Placebo<br>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: Placebo<br>* In the placebo-controlled, double-blind randomisation stage, paclitaxel + placebo will be compared to paclitaxel + IMP321 at the RPTD<br>Drug: Paclitaxel<br>* Paclitaxel will be given in both treatment arms (classified as Non IMP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone receptor positive