Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK

NCT06358573 | Recruiting Phase 2 DMC

• 1 other identifier: SAKK 66/22
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 9

Brief Summary

About 10-20% of all individuals with breast cancer have a so-called triple-negative tumor (TNBC). This type of breast cancer has a particularly unfavorable course and a higher mortality rate compared to other forms of breast cancer. Research studies show that it is important for individuals with TNBC to achieve a so-called pathologic complete response (pCR) to treatment. In the phase II study SAKK 66/22, it is being investigated whether the administration of the drug INT230-6 before surgery for breast cancer can increase the rate of pCR in the tumor and affected lymph nodes. The tolerability of INT230-6 as well as other factors such as response to treatment and the possibility of breast-conserving surgery are also being examined.

Conditions

Triple-negative Breast Cancer; TNBC - Triple-Negative Breast Cancer

Keywords

triple-negative breast cancer; TNBC; Intratumoral INT230-6; neoadjuvant immuno-chemotherapy; INT230-6; early stage

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) in the primary tumor (ypT0/Tis) and affected lymph nodes (ypN0).

  The two following criteria need to be fulfilled for pCR: No invasive breast cancer in primary tumor (noninvasive breast residuals allowed) ypT0/Tis No invasive breast cancer in affected lymph nodes ypN0 The primary endpoint will be analyzed based on the resected patients set. The endpoint is evaluated according to the assessment of the local pathologist.

  At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.

Secondary Outcomes (8)

• pCR (invasive and in-situ, only invasive, respectively) in the breast

  At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.

• pCR in lymph nodes

  At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.

• Pattern of non pCR

  At the date of tumor assessment after surgery, estimated at 29 to 32 weeks after treatment start for cohort A and at 27 to 30 weeks after treatment start for cohort B.

• Overall response according to RECIST v1.1

  At 1 to 4 weeks after last SOC treatment and before surgery, estimated at 27 to 30 weeks after treatment start for cohort A and at 25 to 28 weeks after treatment start for cohort B.

• Radiological tumor response using two perpendicular diameters

  At 1 to 4 weeks after last SOC treatment and before surgery, estimated at 27 to 30 weeks after treatment start for cohort A and 25 to 28 weeks after treatment start for cohort B.

Study Arms (2)

Cohort A experimental

EXPERIMENTAL

Intervention 1 week: \- 1 Injection of INT230-6 into primary tumor of the breast Thereafter * Standard of Care including surgery (30 weeks) * Immuno-chemotherapy -\> 24 weeks Neoadjuvant therapy as Keynote-522 (Standard of Care) - 24 Weeks Pembrolizumab q3W in combination with * Cycles 1-4: Paclitaxel q1W + Carboplatin q1W or q3W * Cycle 5-8: Doxorubicin or Epirubicin q3W + Cyclophospahmide q3W * MRI * Surgery

Drug: INT230-6; Other: neoadjuvant immuno-chemotherapy

Cohort B Standard of Care

OTHER

Intervention 1 week: \- No intervention - start of immune-chemotherapy after randomization Thereafter * Standard of Care including surgery (30 weeks) * Immuno-chemotherapy -\> 24 weeks Neoadjuvant therapy as Keynote-522 (Standard of Care) - 24 Weeks Pembrolizumab q3W in combination with * Cycles 1-4: Paclitaxel q1W + Carboplatin q1W or q3W * Cycle 5-8: Doxorubicin or Epirubicin q3W + Cyclophospahmide q3W * MRI * Surgery

Other: neoadjuvant immuno-chemotherapy

Interventions

INT230-6 DRUG

INT230-6 is a formulation consisting of an proprietary amphiphilic cell penetration enhancer molecule, 8-((2-hydroxybenzoyl)amino)octanoate, also referred to as SHAO, combined with cisplatin and vinblastine sulfate. The IMP is without marketing authorization in Switzerland and anywhere in the world.

Cohort A experimental

neoadjuvant immuno-chemotherapy OTHER

Standard of care

Cohort A experimental; Cohort B Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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: cT1c (1.5-2cm) N1-3 M0 or 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 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 ≥ 1.5cm 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

You may not qualify if:

• Inflammatory Breast Cancer cT4d
• Unfavorable relation between tumor size and breast size as determined by judgement of the treating physician, surgeon and/or investigator, where tumor shrinkage during neoadjuvant immunochemotherapy is required for breast conserving surgery to be considered.
• Unfavorable tumor location that can potentially result in an unfavorable cosmetic outcome (e.g. high upper inner quadrant) and/or close skin contact by judgment of the treating physician, surgeon and/or investigator.
• 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 (including yellow fever vaccine) within 30 days prior to registration.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (9)

Tumor Zentrum Aarau

Aarau, 5000, Switzerland

TERMINATED

St. Claraspital

Basel, 4058, Switzerland

RECRUITING

EOC - IOSI Ospedale regionale Bellinzona e valli - San Giovanni

Bellinzona, 6500, Switzerland

RECRUITING

Kantonsspital Graubünden

Chur, 7000, Switzerland

RECRUITING

Kantonsspital Baselland

Liestal, 4410, Switzerland

RECRUITING

HOCH Health Ostschweiz

Sankt Gallen, 9007, Switzerland

RECRUITING

TBZO - Tumor- & Brustzentrum Ostschweiz

Sankt Gallen, 9016, Switzerland

TERMINATED

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

RECRUITING

Universitätsspital Zürich - Klinik für Gynäkologie

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Markus Joerger, Prof

  HOCH Health Ostschweiz - Kantonsspital St. Gallen

  STUDY DIRECTOR

• Ursina Zürrer, MD

  Kantonsspital Winterthur KSW

  STUDY CHAIR

Central Study Contacts

Jana Musilova, PhD

CONTACT

+41 31 389 91 91; trials@swisscancerinstitute.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, open-label multicenter phase 2 clinical study to determine the clinical activity, safety and tolerability of INT230-6 in patients with early stage, operable TNBC who undergo neoadjuvant systemic treatment.

Study Record Dates

• First Submitted: April 5, 2024
• First Posted: April 10, 2024
• Study Start: October 24, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2031
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

CH (9)