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

211

241

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 52 weeks.

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

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 52 weeks.

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

<p>Inclusion Criteria:</p><p>Key Inclusion</p><ol><li>Able to give written informed consent and to comply with the protocol</li><li>Stage IV oestrogen receptor positive and&#x2F;or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and&#x2F;or metastasis</li><li>Female of age 18 years or above</li><li>Patients who are indicated to received first line chemotherapy with weekly paclitaxel</li><li>All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.</li><li>Eastern Cooperative Oncology Group performance status 0-1</li><li>Expected survival longer than three months transaminases in case of liver metastases</li><li>Evidence of measurable disease as defined by Response Evaluation Criteria version 1.1</li></ol><p>10. Laboratory criteria: haematology and biochemistry results within the limits normally expected for the patient population.</p><p>Exclusion Criteria:</p><ol><li>Prior chemotherapy for metastatic breast adenocarcinoma</li><li>Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy</li><li>Prior high-dose chemotherapy requiring hematopoietic stem cell rescue</li><li>Inflammatory carcinoma</li><li>Candidate for treatment with trastuzumab (or other Her2&#x2F;neu targeted agents)</li><li>Systemic chemotherapy, endocrine therapy, or any other investigational agent within 4 weeks prior to first dose of study treatment and until completion of study treatment</li><li>Known cerebral or leptomeningeal metastases</li><li>Women who are pregnant or lactating</li><li>Serious intercurrent infection within 4 weeks prior to first dose of study treatment</li><li>QTcF &gt;480 ms, family or personal history of long or short QT syndrome, Brugada syndrome or known history of controlled QT prolongation, or Torsade de Pointes (TdP)</li><li>Uncontrolled electrolyte disorders that can worsen the effects of a corrected QT-prolonging drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia)</li><li>Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment including: myocardial infarction, severe&#x2F;unstable angina, ongoing cardiac dysrhythmias of NCI Common Toxicity Criteria for adverse events version 4.03 Grade ≥2, atrial fibrillation of any grade, coronary&#x2F;peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, ventricular arrhythmias requiring medication or symptomatic pulmonary embolism</li><li>Active acute or chronic infection</li><li>Active autoimmune disease requiring immunosuppressive therapy</li><li>Known HIV positivity</li><li>History of Hepatitis B or C exposure, currently controlled by antiviral therapy</li><li>Life threatening illness unrelated to cancer</li><li>Previous malignancies within the last three years other than breast carcinoma, except successfully treated squamous cell carcinoma of the skin, superficial bladder cancer, and in situ carcinoma of the cervix</li><li>Any current disorder that would impede the patient&#x27;s ability to provide informed consent or to comply with the protocol</li><li>Any condition requiring continuous systemic treatment with either corticosteroids (&gt;10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.
Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease</li><li>Past history of severe allergic episodes and&#x2F; or Quincke&#x27;s oedema</li><li>Alcohol or substance abuse disorder</li><li>Known hypersensitivity to any of the components of the study agents</li><li>Participation in another clinical study within 4 weeks prior to screening</li><li>Unwilling or unable to follow protocol requirements</li><li>In the clinical judgment of the Investigator, the patient is unsuitable for participation in this study</li><li>Persons with any kind of dependency on the Investigator or employed by the sponsor or Investigator</li><li>Persons held in an institution by legal or official order</li></ol>

<p>Inclusion Criteria:</p><ol><li>Able to give written informed consent and to comply with the protocol</li><li>Stage IV oestrogen receptor positive and&#x2F;or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and&#x2F;or metastasis</li><li>Female of age 18 years or above</li><li>Patients who are indicated to received first line chemotherapy with weekly paclitaxel</li><li>Evidence of measurable disease as defined by Response Evaluation Criteria version 1.1</li></ol><p>6 Laboratory criteria: haematology and biochemistry results within the limits normally expected for the patient population.</p><p>Exclusion Criteria:</p><ol><li>Prior chemotherapy for metastatic breast adenocarcinoma</li><li>Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy</li><li>Inflammatory carcinoma</li><li>Candidate for treatment with trastuzumab (or other Her2&#x2F;neu targeted agents)</li><li>Systemic chemotherapy,radiation therapy or any other investigational agent within 4 weeks, endokrine therapy within 1 week prior to first dose of study treatment and until completion of study treatment</li><li>Symptomatic known cerebral and&#x2F;or leptomeningeal metastases</li><li>Serious intercurrent infection</li><li>Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment</li><li>Active acute or chronic infection</li><li>Active autoimmune disease requiring immunosuppressive therapy</li><li>Previous malignancies within the last three years other than breast carcinoma</li><li>Patients with prior organ or stem cell transplantation</li><li>Any condition requiring continuous systemic treatment with either corticosteroids or other immunosuppressive medications within 4 weeks prior to first dose of study treatment.</li></ol>

Assessment of the safety and tolerability of IMP321 as compared to placebo (adverse events and serious adverse events, physical examinations, vital signs, safety lab, ECG)

Assessment of the safety and tolerability of IMP321 as compared to placebo

Up to 37 month

Up to 48 month

Up to 6 months

Up to 12 months

Evaluation of the time to next treatment. This is defined as the time between the date of first study treatment administration and the start of the next anti-cancer treatment

Evaluation of the time to next treatment

Evaluation of stable disease. This is defined as the time (days) from the date study administration to the date of disease progression or death (if death occured before progression)

Evaluation of stable disease

2019-06

2020-12

2016-10-16

2017-01-13

2016-10-18

2017-01-18

Stage 1: assessment of Immuno-monitoring in a defined subset of 60 patients during the randomised stage. Blood samples of this patients will be taken to assess Monocytes/Lymphocytes Count Cell Activation

Stage 1: assessment of Immuno-monitoring in a defined subset of 60 patients during the randomised stage