Direct injection of the substance INT230-6 into the tumor, followed by neoadjuvant treatment with chemo-immunotherapy, in patients with early triple-negative breast cancer: an open-label, randomized phase II study with two groups of participants (cohorts)

Switzerland (ICTRP)

ICTRP Studien-ID
NCT06358573 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
SAKK 66/22 Intratumoral INT230-6 followed by neoadjuvant Pembrolizumab and chemotherapy in patients with early triple-negative breast cancer (TNBC). An open-label randomized two-cohort phase 2 clinical trial. (BASEC)

Wissenschaftlicher Titel
Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early Triple-negative Breast Cancer (TNBC). An Open-label Randomized Two-cohort Phase 2 Clinical Trial. INVINCIBLE-4-SAKK (ICTRP)

Öffentlicher Titel
Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK (ICTRP)

Untersuchte Krankheit(en)
Triple-negative Breast CancerTNBC - Triple-Negative Breast Cancer (ICTRP)

Untersuchte Intervention
Drug: INT230-6Other: neoadjuvant immuno-chemotherapy (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Ein-/Ausschlusskriterien
Inclusion Criteria:

- Written informed consent according to country specific law and ICH GCP E6(R2)
regulations before registration and prior to any trial specific procedures.

- Newly histologically diagnosed, previously untreated locally advanced non-metastatic
TNBC as defined by the most recent American Society of Clinical Oncology (ASCO) /
College of American Pathologist (CAP) guidelines .

- The following stages according to staging per American Joint Committee on Cancer
(AJCC) for breast cancer staging criteria version 8 are included: cT2-4c N0-3 M0.

- Multifocal and multicentric primary tumors are allowed and the tumor with the most
advanced T stage should be used to assess the eligibility. If multifocal or
multicentric disease TNBC needs to be confirmed for each focus.

- Measurable disease in the breast with at least one lesion with a diameter =2cm that
is evaluable per RECIST v1.1, visible in ultrasound and injectable.

- Male or female subject Age = 18 years.

- ECOG performance status 0-1

- Adequate bone marrow function (administration of G-CSF, EPO and/or blood transfusion
within 14 days before registration is not allowed):

- neutrophil count = 1.5 x 109/L

- platelet count = 100 x 109/L

- hemoglobin = 90 g/L

- Adequate hepatic function:

- total bilirubin = 1.5 x ULN, or direct bilirubin = ULN for subjects with total
bilirubin levels > 1.5 x ULN

- AST and ALT = 2.5 x ULN,

- Albumin 30 = g/L

- Lactate Dehydrogenase (LDH) <2.5 ULN

- Adequate renal function: estimated glomerular filtration rate (eGFR) = 50
ml/min/1.73 m2 (according to CKD-EPI formula or serum creatinine = 1.5x ULN.

- Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) = 50% as
determined by echocardiography (ECHO)

- Adequate coagulation function:

- INR = 1.5 x ULN unless patient is receiving anticoagulant therapy

- aPTT = 1.5 x ULN unless patient is receiving anticoagulant therapy

- If patient is receiving anticoagulant therapy, the treating physician must
determine that the anticoagulation can be stopped at least 24 hours prior to
injection.

- Women of childbearing potential must use highly effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
until 6 months after the last dose of INT230-6 or standard of care treatment. A
negative pregnancy test before inclusion into the trial is required for all women of
childbearing potential. (www.swissmedicinfo.ch).

- Men agree not to donate sperm or to father a child during trial treatment and until
6 months after the last dose of INT230-6 or standard of care treatment
(www.swissmedicinfo.ch).

Exclusion Criteria:

- Inflammatory Breast Cancer cT4d

- The following histological subtypes of TNBC are excluded: Classic adenoid cystic
carcinoma, secretory carcinoma, low-grade adenosquamous carcinoma, tall cell
carcinoma with reversed polarity, high-grade metaplastic

- History of invasive malignancy =3 years prior to signing informed consent (except
treated basal cell or squamous cell skin cancer or in situ cervical cancer)

- Prior chemotherapy, targeted therapy, radiation therapy or anti-PD-L1 agent for
previous breast cancer or Ductal Carcinoma in Situ (DCIS) on the same side.

- Concurrent bilateral breast cancer

- Concomitant treatment with any other experimental drug for recent breast cancer
diagnosis in another clinical trial.

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA II or
IV unstable angina pectoris, history of myocardial infarction and acute coronary
syndrome requiring stenting/bypass surgery within the last six months, serious
arrhythmias requiring medication (with exception of atrial fibrillation or
paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled
hypertension.

- Known history of human immunodeficiency virus (HIV) or active chronic hepatitis C or
hepatitis B virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment.

- Active autoimmune disease that required systemic treatment in past 2 years (e.g.,
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g., thyroid hormone replacement, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not
considered a form of systemic treatment.

- History of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

- Known history of tuberculosis.

- Known history of allogeneic organ or stem cell transplant.

- Receipt of live attenuated vaccine within 30 days prior to registration.

- Diagnosis of immunodeficiency, concomitant or prior use of immunosuppressive
medication within 7 days before registration, with the exceptions of local
(intranasal, topical and inhaled) corticosteroids, or systemic corticosteroids which
must not exceed 10 mg/day of prednisone or a dose equivalent corticosteroid, and the
premedication for chemotherapy.

- Concomitant anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.
phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin
inhibitors (e.g. dabigatran) or platelet inhibitors/antiplatelet agents that cannot
be stopped 24 hours before the administration of INT230-6. Aspirin (up to 300
mg/day) is allowed.

- Any concomitant drugs contraindicated for use with the trial drug according to the
Investigator Brochure (IB) and the immuno-chemotherapy treatment according to the
approved product information.

- Known hypersensitivity to trial drug or to any component of the trial drug or
immuno-chemotherapy treatment.

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications. (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Pathological complete response (pCR) in the primary tumor (ypT0/Tis) and affected lymph nodes (ypN0). (ICTRP)

pCR (invasive and in-situ, only invasive, respectively) in the breast;pCR in lymph nodes;Pattern of non pCR;Overall response according to RECIST v1.1;Radiological tumor response using two perpendicular diameters;Event free survival (EFS);Rate of breast conserving surgery (BCS) at the time of definitive surgery;Conversion of intention for mastectomy to BSC and axillary lymph node dissection (ALND) to sentinel lymph node dissection (SLND) or tailored axillary surgery (TAS) after treatment (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Markus Joerger, Prof;Ursina Z?rrer, MD;Katrin Eckardt, PhD, trials@sakk.ch, +41 31 389 91 91, Cantonal Hospital of St. Gallen,Kantonsspital Winterthur KSW, (ICTRP)

Sekundäre IDs
SAKK 66/22 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06358573 (ICTRP)