A clinical trial with nadunolimab in combination with gemcitabine plus carboplatin in patients with advanced triple negative breast cancer. TRIFOUR study”.

Phase 1

Active, not recruiting

• Conditions: nresectable locally advanced or metastatic triple negative breast cancer.; MedDRA version: 23.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-003402-46-ES
• Lead Sponsor: Cantargia AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-06
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

1. The patient has signed and dated the informed consent form (ICF) and it has been obtained before conducting any specific procedure for the study.
2. Female or male BC patients of = 18 years of age.
3. Permission to access archived tumor tissue sample (either from primary breast tumor or a metastatic lesion, preferably the most recent one) for biomarker analysis. Not having archived tissue is not a reason to exclude the patient from enrollment.
4. Paired tumor biopsies, pre-treatment and on-treatment, for pharmacodynamic analysis are not compulsory and will be obtained as per investigator judgement and patient decision. However, patients and investigators are encouraged to obtain them if the patient has easily accessible disease like skin or superficial lymph nodes. Ideally, the same lesion (always in the same organ) should be biopsied before treatment and on treatment whenever possible. It is allowed to use archived biopsies as pre-treatment samples, obtained after ending the previous systemic treatment).
5. The lesion accessible for biopsy may not be the only target lesion and should not be located in a previously irradiated field (unless this index lesion has PD = 20% post-radiation).
6. Histologically confirmed TNBC that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic:
a. Documented Hormone Receptor (HR) negative BC based on local laboratory determination on the most recent tumor biopsy. HR negative defined as < 1% positive cells by immunohistochemistry (IHC) for estrogen receptor (ER) and progesterone receptor (PgR).
b. Documented Human Epidermal Growth Factor Receptor 2 (HER2) negative BC based on local laboratory determination on the most recent tumor biopsy. HER2 negative tumor is determined according to recommendations of the applicable ASCO/ CAP guidelines available.
c. Patients are eligible for the study irrespectively of BRCA1/2 mutational status. It is not required to have the analysis performed before the study inclusion.
7. Patients should be eligible to receive gemcitabine and carboplatin as the following line of therapy. No more than 1 previous lines of systemic therapy for the advanced disease are allowed:
a. Those patients with PD during or within 6 months after completing the (neo)adjuvant treatment are allowed to be included in the study and are considered for second-line group of patients.
b. Prior therapy with immunocheckpoint inhibitors (ICIs) either in the metastatic setting (as first-line therapy) or in the (neo)adjuvant setting is allowed.
c. Previous treatment with platinum-derived agents in early-stage setting is allowed if the platinum-free interval is at least of 12 months.
d. Prior therapy with PARP inhibitors is allowed.
8. Documented progressive disease (i.e. biopsy sample, pathology or imaging report) from the last treatment.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status = 1.
10. Patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT scan, MRI, plan X-ray or physical examination. Clinical lesions will only be considered measurable when they are superficial and = 10mm in diameter as assessed using callipers (e.g. skin nodules). Patients with bone-only disease must have a lytic or mixed (lytic + blastic) lesion, which has not been previously irradiated and can be accurately assessed by CT scan/MRI according to RECIST version 1.1 (with a

Exclusion Criteria

1. Patient has received extended field radiotherapy = 4 weeks before the start of treatment (= 2 weeks for limited field radiation for palliation), and who has not recovered to = Grade 1, according to NCI CTCAE v5.0, from related AEs of such therapy (except for alopecia). 2. Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter. Patients should have recovered from previous treatment toxicity to = Grade 1 (except alopecia and peripheral neuropathy). 3. No prior treatment with an anthracycline and a taxane unless contraindicated or not considered the most suitable treatment option (e.g. in the de novo metastatic setting) according to physician’s opinion.
4. Significant cardiovascular disease, such as NYHA cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomisation, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) < 50% will be
excluded. 5. Patients with known coronary artery disease or CHF not meeting the above criteria, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. 6. Presence of an abnormal ECG that is clinically significant in the investigator’s opinion, including complete left bundle branch block, second or third-degree heart block, or QTcF > 480 ms demonstrated by at least two consecutive ECGs.
7. Patients with uncontrolled brain metastases; however, patients who have been previously treated with surgery, whole-brain radiation, and/or stereotactic radiosurgery and are considered controlled (with = 10 mg/day of prednisone or equivalent) at the time of receiving the first dose of nadunolimab are allowed. For asymptomatic patients, screening brain imaging is not required. 8. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to enrolment. 9. Severe (Grade 3) infection requiring oral or IV antibiotics within 4 weeks prior to enrolment, including but not limited to hospitalization for complications of infection, bacteremia, or pneumonia. Patients receiving prophylactic antibiotics are eligible for the study. 10. Patients testing positive for HIV are NOT excluded from this study, but HIV-positive patients must meet ALL the following criteria: a. Have CD4+ T-cell (CD4+) counts = 350 cells/mL. b. Have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the study. c. Should be on stable antiretroviral therapy for at least 4 weeks. d. Have an HIV viral load less than 400 copies/mL prior to enrolment.
11. Negative HBsAg test at screening. Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. Patients who have a positive HBcAb test should have negative viral load. 12. Negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. 13. Pregnant or lactating or intending to become pregnant during or within 6 months afte

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified