A Study in Hormone Receptor-positive Metastatic Breast Carcinoma Patients to Test a New Schedule of Efti (IMP321, Eftilagimod Alpha) as Adjunctive to a Weekly Treatment Regimen of Paclitaxel

Study Overview
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Brief Summary
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This is a multicentre, multinational Phase Ib study in female HR+ MBC patients not receiving Her2-targeted therapy. Treatment consists of a chemo-immunotherapy phase followed by a maintenance phase. The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 80 mg/m2 paclitaxel intravenously on Day 1, 8 and 15 and 30 mg efti subcutaneously on Day 1 and 15 in a 28-day (4-week) cycle. Efti will always be given after paclitaxel. The maintenance phase comprises 6 visits with 4 weekly intervals; during each such visit 30 mg efti is given subcutaneously as monotherapy. A total of 24 subjects will be enrolled into the study. The primary goal of the study is safety and tolerability profile of efti in combination with weekly paclitaxel both given the same day in contrast to subsequent days as in the AIPAC trial.

Detailed Description
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This is a multicentre, multinational Phase Ib study in female HR+ MBC patients not receiving Her2-targeted therapy. Treatment consists of a chemo-immunotherapy phase followed by a maintenance phase. The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 80 mg/m2 paclitaxel intravenously on Day 1, 8 and 15 and 30 mg efti subcutaneously on Day 1 and 15 in a 28-day (4-week) cycle. Efti will always be given after paclitaxel. The maintenance phase comprises 6 visits with 4 weekly intervals; during each such visit 30 mg efti is given subcutaneously as monotherapy. A total of 24 subjects will be enrolled into the study. The primary goal of the study is safety and tolerability profile of efti in combination with weekly paclitaxel both given the same day in contrast to subsequent days as in the AIPAC trial.

Official Title
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AIPAC-002 (Active Immunotherapy PAClitaxel-002): A Multicentre, Phase Ib Study to Test a New Schedule of Eftilagimod Alpha (a Soluble LAG-3 Protein) as Adjunctive to Weekly Paclitaxel in Hormone Receptor-positive Metastatic Breast Carcinoma Patients

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Eftilagimod Alpha
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (selected ones): Metastatic oestrogen receptor positive and/or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and/or a metastasis Subjects who are indicated to receive first line chemotherapy with weekly paclitaxel ECOG performance status 0-1 Expected survival longer than three months Exclusion Criteria (selected ones): Prior chemotherapy for metastatic breast adenocarcinoma Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy Prior high-dose chemotherapy requiring hematopoietic stem cell rescue Inflammatory carcinoma at time of screening Candidate for treatment with trastuzumab (or other Her2/neu targeted agents) or endocrine based therapy according to the applicable treatment guidelines Systemic chemotherapy, radiation therapy or any other investigational agent within 4 weeks, endocrine therapy within 1 week or CDK4/6 inhibitors within 5 times half-life (acc. to SPC) prior to first dose of study treatment Symptomatic known cerebral and/or leptomeningeal metastases

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eftilagimod alpha + Paclitaxel<br>The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 80 mg/m2 paclitaxel intravenously on Day 1, 8 and 15 and 30 mg efti subcutaneously on Day 1 and 15 in a 28-day (4-week) cycle. Efti will always be given after paclitaxel. The maintenance phase comprises 6 visits with 4 weekly intervals; during each such visit 30 mg efti is given subcutaneosuly as monotherapy. | Drug: Eftilagimod Alpha<br>* The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 30 mg efti subcutaneously on Day 1 and 15 in a 28-day (4-week) cycle. Efti will always be given after paclitaxel. The maintenance phase comprises 6 visits with 4 weekly intervals; during each such visit 30 mg efti is given subcutaneosuly as monotherapy.<br>* Other names: IMP321; efti;Drug: Paclitaxel<br>* The chemo-immunotherapy phase consists of 6 cycles of 4 weeks each. During each cycle the subject will receive 80 mg/m2 paclitaxel intravenously on Day 1, 8 and 15.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability profile of efti in combination with weekly paclitaxel both given the same day | Severity, frequency and duration of adverse events | up to 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of efti given on the same day as paclitaxel | AUC after 1st injection of efti | up to 12 month | 
| Cmax of efti given on the same day as paclitaxel | Cmax after 1st injection of efti | up to 12 month | 
| Tmax of efti given on the same day as paclitaxel | Tmax after 1st injection of efti | up to 12 month | 
| Peripheral IFN-gamma concentration in the blood | Changes IFN-gamma concentration in course of treatment with efti | up to 12 month | 
| Peripheral IP-10 concentration in the blood | Changes IP-10 concentration in course of treatment with efti | up to 12 month | 
| Overall response rate of efti in combination with weekly paclitaxel both given the same day | Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria | up to 12 month | 
| Median progression free survival of efti in combination with weekly paclitaxel both given the same day | The median progression free survival with the use of efti in combination with Paclitaxel | up to 20 month | 
| Median overall survival of efti in combination with weekly paclitaxel both given the same day | The median time frame with overall survival with the use of efti in combination with Paclitaxel | up to 20 month | 
| To characterise immunogenic properties of efti in combination with weekly paclitaxel both given the same day | Screen for possible ADA | up to 12 month |