Female metastasized oestrogen receptor positive and/or progesterone receptor positive breast adenocarcinoma MedDRA version: 20.0 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: IMP321
Pharmaceutical Form: Solution for injection
INN or Proposed INN: eftilagimod alfa
CAS Number: 1800476-36-1
Other descriptive name: IMP321
Concentration unit: mg/ml milligram(s)/mi
Sponsors
Immutep S.A.S.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to give written informed consent and to comply with the protocol 2.1 Metastasized oestrogen receptor positive and/or progesterone receptor positive breast adenocarcinoma, histologically proven by biopsy of the primary tumour and/or a metastasis 3. Female of age 18 years or above 4. Patients who are indicated to received first line chemotherapy with weekly paclitaxel 5.1 All patients of childbearing potential must have a negative highly sensitive pregnancy test at screening and agree to use highly effective method for contraception according to the EU Clinical Trial Facilitation Group guidance from time of study entry until at least 6 months after the last administration of study drug. The partners of patients with childbearing potential must also apply contraceptive methods. Patients who are either , o postmenopausal (= 60 years of age, or =65 years) yes F.1.3.1 Number of subjects for this age range 121
Exclusion criteria
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. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue 4.1 Inflammatory carcinoma at time of screening 5.1 Candidate for treatment with trastuzumab (or other Her2/neu targeted agents) or endocrine based therapy according to the applicable treatment guidelines 6.2 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 7.1 Symptomatic known cerebral and/or leptomeningeal metastases 8. Women who are pregnant or lactating 9. Serious intercurrent infection within 4 weeks prior to first dose of study treatment 10. QTcF >480 ms, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP) 11. Uncontrolled electrolyte disorders that can worsen the effects of a QTc-prolonging drug (e.g., hypocalcaemia, hypokalaemia, hypomagnesemia) 12.1 Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 Grade =2, atrial fibrillation , coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, ventricular arrhythmias requiring medication or symptomatic pulmonary embolism 13. Active acute or chronic infection 14. Active autoimmune disease requiring immunosuppressive therapy 15.1 Positive test for HIV 16.1 Positive test for Hepatitis B (anti–HBc) or C (Patients who are anti- HBc+ and HBsAg negative are eligible and are not excluded from participation in this study) 17. Life threatening illness unrelated to cancer 18. 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 19. Any current disorder that would impede the patient's ability to provide informed consent or to comply with the protocol 20. Any condition requiring continuous systemic treatment with either corticosteroids (>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 21. Past history of severe allergic episodes and/ or Quincke's oedema 22. Alcohol or substance abuse disorder 23. Known hypersensitivity to any of the components of the study agents 24.1 Participation in an interventional clinical study within 4 weeks prior to first dose of study treatment, with intervention not covered by exclusion criterion 6.2 25. Unwilling or unable to follow protocol requirements 26. In the clinical judgment of the Investigator, the patient is unsuitable for participation in this study 27. Persons with any kind of dependency on the Investigator or employed by the sponsor or Investigator 28. Persons held in an institution by legal or official order 29. Patients with prior organ or stem cell transplantation 30. Patients having received a live, attenuated vacci
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives: ? Safety run-in stage: To determine the recommended phase two dose for the randomised stage ? Randomised stage: to determine efficacy of IMP321 combined with weekly paclitaxel compared to weekly paclitaxel plus placebo in hormone receptor-positive metastatic breast cancer patients;Secondary Objective: Secondary objectives: ? to further characterise the anti-tumour activity of IMP321 in combination with weekly paclitaxel in terms of clinical responses and clinical outcomes and compare it to placebo ? to examine the safety and tolerability of IMP321 in combination with weekly paclitaxel and compare it to placebo ? to characterise the pharmacokinetic (safety run-in stage only) and immunogenic properties of IMP321 ? to assess the quality of life related to IMP321 compared to placebo;Primary end point(s): Stage 1: to determine DLTs and the recommended phase II dose Stage 2: To determine progression free survival (PFS) ;Timepoint(s) of evaluation of this end point: Radiology assessments in the treatment phase will be every 8 weeks until week 73. It may bue performed ±3 days prior to that specific radiological assessment during the chemo-immunotherapy phase and ± 7 days during the maintenance and follow-up phase. PFS at Follow-Up Visits every 12 weeks (± 1 week) until PD, start of next line of therapy, withdrawal of consent, loss to follow-up, death from any cause, or the end of the study (whichever occurs first). For patients who prematurely discontinue treatment for any reason except PD, PFS Follow-Up Visits will occur every 8 weeks until weeks 73 and every 12 weeks thereafter dependent on the most recent radiological assessment prior to discontinuation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints • To assess overall survival (OS) • To assess adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and other safety parameters • To assess the time to next treatment (TTNT), objective response rate (ORR) according to RECIST 1.1, time to and duration of response and duration of stable disease • To assess the plasma concentration time profile of IMP321 and derived PK parameters • To assess the quality of life (QOL) • To assess development of anti-drug (IMP321) antibodies (ADA);Timepoint(s) of evaluation of this end point: OS: After documented PD, every 12 weeks after enrolment into the trial for the first 2 years and every 24 weeks thereafter (± 4 weeks). Other efficacy parameters (TTNT, ORR, time to and duration of response, duration of stable disease) at same timepoints as PFS and OS. (S)AEs will be collected from the time of ICF signature until 30 days after last study drug administration, and after this period only when considered (in the opinion of the Investigator) related to study treatment. PK parameters: run-in stage only at cycle 1 day 2, 3 and 4 and cycle 6 day 16, 17 and 18. QoL: Chemo-immunotherapy phase visit 1 and visit 16; Maintenance phase visit 31 and visit 37; At end of treatment, visit 43. ADA: at screening, visit 6, 11, 21, 31, 34, 37, 40 and at end of treatment. | — |
Countries
Belgium, Germany, Hungary, Netherlands, Poland, United Kingdom
Contacts
Public ContactAnnika Tintel
CATO SMS
Outcome results
None listed