EFTILAGIMOD ALFA for Metastatic breast cancer (HER2-negative/low)

Inclusion criteria

• {"criterion_text":"- 1. Able to give written informed consent and to comply with the protocol. Note: signed and dated informed consent must be obtained prior to any protocol related procedure.\n- 10. Resolution of toxicity of prior therapy to grade <2 (except for transaminases in the presence of liver metastases and for alopecia where grade 2 is allowed).\n- 11. Patients who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.\n- 12. Patients with a history of HCV infection are eligible if HCV viral load is undetectable at screening.\n- 13. HIV infected patients must be on antiretroviral therapy and have a well-controlled HIV infection/disease defined as: a. Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening. b. Patients on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening. c. Patients on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to cycle 1 day 1.\n- 14. Laboratory criteria: a. Total white cell count ≥3 x 10^9/L b. Platelet count ≥100 x 10^9/L c. Hemoglobin ≥9 g/dL or 5.58 mmol/L d. Absolute Neutrophil Count (ANC) ≥1.5 x 10^9/L e. Estimated glomerular filtration rate by CKD-EPI >30 mL/min f. Total bilirubin ≤20 μmol/L, except for familial cholemia (Gilbert's disease) g. Serum ASAT and ALAT ≤3 times ULN or ≤5 times ULN if liver metastases are present. Please refer to the protocol for the full inclusion criteria with notes.\n- 2. Metastatic HR+ (estrogen receptor positive and/or progesterone receptor positive) or hormone receptor negative (HR-), and HER2- neg/low breast adenocarcinoma, histologically proven by biopsy last available tumor tissue (primary tumor and/or a metastasis; metastasis preferred).\n- 3. Patients with HR+ MBC who progressed on or after ≥1 line of endocrine based therapy and are indicated to receive paclitaxel chemotherapy for metastatic disease, in line with locally applicable treatment guidelines and local standard of care. Meeting any of below conditions: a. Primary endocrine resistance: recurrence/relapse ≤2 years after the start of adjuvant endocrine therapy for early breast cancer, or progression within 6 months of 1st line endocrine based therapy for metastatic breast cancer. b. Secondary endocrine resistance: recurrence/relapse >2 years after starting adjuvant endocrine based therapy, recurrence/relapse <12 months of finishing adjuvant endocrine based therapy or progression after >6 months of endocrine based therapy for metastatic breast cancer.\n- 4. Patients with TNBC who are indicated to receive paclitaxel chemotherapy without anti-PD-1/PD-L1 therapy in the 1st line setting for metastatic disease, in line with locally applicable treatment guidelines and local standard of care.\n- 5. Dose optimization lead-in: Female of age 18 years-of-age or older. Phase 3: Female or male of age 18 years-of-age or older.\n- 6. All patients of childbearing potential must have a negative highly sensitive pregnancy test at screening and agree to use a highly effective method for contraception according to the EU Clinical Trial Facilitation Group guidance from time of trial entry until at least 6 months after the last administration of the trial drug. The partners of patients with childbearing potential must also apply contraceptive methods. Patients who are either: a. Postmenopausal (≥60 years of age, or <60 years of age and amenorrhoeic for 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with follicle-stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L; or if taking tamoxifen or toremifene, and age <60 years, then FSH and estradiol in the postmenopausal range), permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy), b. Incapable of pregnancy are not considered to be of childbearing potential.\n- 7. Dose optimization lead-in only: evidence of measurable disease as defined by RECIST 1.1.\n- 8. ECOG performance status 0-1.\n- 9. Expected survival longer than three months."}

Exclusion criteria

• {"criterion_text":"- 1. Prior chemotherapy for metastatic breast adenocarcinoma.\n- 10. Women who are pregnant or lactating.\n- 11. Serious intercurrent infection treated with parenteral antibiotics within 4 weeks prior to first dose of trial treatment.\n- 12. 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).\n- 13. Uncontrolled electrolyte disorders of grade 2 or higher severity that may worsen the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia).\n- 14. Evidence of severe or uncontrolled cardiac disease within 6 months prior to first dose of trial treatment including: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 5.0 Grade ≥2, atrial fibrillation, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA III-IV), cerebrovascular accident including transient ischemic attack, ventricular arrhythmias requiring medication or symptomatic pulmonary embolism.\n- 15. Active acute or chronic infection (exceptions are defined in Incl. crit. #11-13).\n- 16. HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.\n- 17. Active or past autoimmune disease requiring systemic immunosuppressive therapy in the past 2 years. Replacement therapy is allowed.\n- 18. 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 trial 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.\n- 19. Life threatening illness unrelated to cancer.\n- 2. Patients with HR+ MBC who have received <1 line of ET based therapy in the metastatic setting.\n- 20. Previous malignancies within the last three years other than breast cancer, except successfully treated squamous cell carcinoma of the skin, superficial bladder cancer, in situ carcinoma of the cervix and tamoxifenrelated endometrial cancer definitively treated with hysterectomy.\n- 21. Patients with prior organ or stem cell transplantation.\n- 22. Live vaccine within 30 days of planned C1D1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.\n- 23. Patients treated with systemic immune stimulatory agents (excluding vaccines) within 6 weeks or five half-lives of the drug prior to first administration of trial treatment.\n- 24. History of severe allergic episodes and/ or Quincke's oedema.\n- 25. Known hypersensitivity to any of the components of the trial agents.\n- 26. Participation in another interventional clinical trial with last trial treatment given within 4 weeks prior to C1D1, with intent other than covered by Exclusion criterion #8.\n- 27. Any current disorder that would impede the patient's ability to provide informed consent or to comply with the protocol, or in the clinical judgement of the Investigator, the patient is unsuitable for participation in this trial for any reason.\n- 28. Persons with any kind of dependency on the Investigator or employed by the Sponsor or Investigator; persons held in an institution by legal or official order.\n- 3. Patients with HR+ MBC who are not primary or secondary resistant to ET-based therapy and would be candidates to ET based therapy as per applicable treatment guidelines.\n- 4. TNBC patients who are candidates for PD-1/PD-L1 therapy in combination with chemotherapy.\n- 5. Disease-free interval of less than twelve months from the last dose of adjuvant chemotherapy.\n- 6. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.\n- 7. Inflammatory breast cancer at the time of screening.\n- 8. Any (investigational) agent given with intent to treat breast cancer within 4 weeks, while for endocrine therapy within 1 week and for treatment with CDK4/6 inhibitors within 5 times half-life (according to SPC) prior to first dose of trial treatment.\n- 9. Symptomatic known cerebral and/or leptomeningeal metastases."}

Primary endpoints

• {"endpoint_text":"- DOSE OPTIMIZATION LEAD-IN • Frequency, severity, and duration of adverse events (AEs). • Clinically relevant abnormalities in vital signs, physical examinations, 12-lead ECGs, and safety laboratory assessments. • Occurrence of dose-limiting toxicities (DLTs). • Determination of the OBD.","definition_or_measurement_approach":"Safety and tolerability will be assessed by frequency, severity, and duration of AEs, clinically relevant abnormalities in vital signs, physical exams, 12-lead ECGs and safety labs; DLTs occurrence will be recorded; determination of optimal biological dose (OBD) based on these safety and tolerability assessments."}
• {"endpoint_text":"- PHASE 3 • Overall survival (OS) is defined as the time from randomization to death from any cause.","definition_or_measurement_approach":"OS measured as time from randomization to death from any cause; standard survival analysis (time-to-event) with censoring at last known alive or data cut-off."}

Secondary endpoints

• {"endpoint_text":"- DOSE OPTIMIZATION LEAD-IN • Objective response rate (ORR) according to RECIST 1.1 by investigator assessment defined as the proportion of patients who have best overall response (BOR) of CR or PR.","definition_or_measurement_approach":"ORR per RECIST 1.1 by investigator assessment; proportion of patients with BOR of complete response (CR) or partial response (PR)."}
• {"endpoint_text":"- • Progression free survival (PFS) per RECIST 1.1, defined as the timefrom the date of first treatment to documented disease progression or death from any cause as assessed by the investigator assessment based on RECIST 1.1. Censuring rules as per FDA guideline. .","definition_or_measurement_approach":"PFS per RECIST 1.1 measured from date of first treatment to documented progression or death; investigator-assessed; censoring rules per FDA guidance."}
• {"endpoint_text":"- • Overall survival (OS) is defined as the time from the date of first treatment to death from any cause. Patients who are lost to follow-up and those who are alive at the date of data cut-off will be censored at the last date the patient was last known alive, or date of data cut-off, whichever occurs first.","definition_or_measurement_approach":"OS measured from date of first treatment to death from any cause; censoring at last known alive date or data cut-off for those alive or lost to follow-up."}
• {"endpoint_text":"- • Changes from baseline in quality of life (QOL) as assessed by EORTC QLQ-C30 over the course of the trial.","definition_or_measurement_approach":"QOL assessed using EORTC QLQ-C30 with changes from baseline evaluated over time."}
• {"endpoint_text":"- • Plasma concentration time profile and derived PK parameters of efti at 30 and 90 mg (dose optimization lead-in only) dose levels.","definition_or_measurement_approach":"Pharmacokinetic sampling to determine plasma concentration-time profiles and PK parameters (e.g., Cmax, AUC) for efti at 30 mg and 90 mg."}
• {"endpoint_text":"- • Progression free survival (PFS) per RECIST 1.1, defined as the time from randomization to documented disease progression or death from any cause as assessed by the investigator assessment based on RECIST 1.1. Censuring rules as per FDA guideline.","definition_or_measurement_approach":"PFS per RECIST 1.1 measured from randomization to progression or death; investigator-assessed; censoring rules per FDA guidance."}
• {"endpoint_text":"- • Objective response rate (ORR) according to RECIST 1.1 by investigator assessment defined as the proportion of patients who have best overall response (BOR) of CR or PR.","definition_or_measurement_approach":"ORR per RECIST 1.1 by investigator assessment; proportion achieving CR or PR."}
• {"endpoint_text":"- • Frequency, severity, and duration of adverse events (AEs)","definition_or_measurement_approach":"Safety monitoring and AE reporting according to CTCAE criteria; summary of frequencies, grades and durations."}
• {"endpoint_text":"- • Clinically relevant abnormalities in vital signs, physical examinations, 12-lead ECGs, and safety laboratory assessments.","definition_or_measurement_approach":"Regular safety assessments including vital signs, physical exams, 12-lead ECGs and laboratory tests to identify clinically relevant abnormalities."}

Spain

Earliest CTIS Part Ii Submission Date

06-06-2024

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

501

Number Of Sites

9

Number Of Participants

63

Belgium

Earliest CTIS Part Ii Submission Date

06-06-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

670

Number Of Sites

5

Number Of Participants

36

Primary sponsor

Full Name

Immutep

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Fortrea Development Limited

Responsibilities

Sponsor duties codes listed in application: 10,12,2,5,6,7,8,9 (responsibilities provided as codes in record); contact email: Submissions@fortrea.com

Third parties

• {"country":"France","full_name":"Phinc Development","duties_or_roles":"Other","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Charles River Laboratories Evreux","duties_or_roles":"Oher","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Allucent (Belgium)","duties_or_roles":"SAFETY REPORTING","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fortrea Development Limited","duties_or_roles":"codes: 10,12,2,5,6,7,8,9 (multiple responsibilities listed)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Other","organisation_type":"Pharmaceutical company"}