Thero2-01S22 in HER2-positive Breast Cancer

NCT05698186 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2022-009
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

Brief Summary

Trastuzumab and pertuzumab based regimen are the standard of care for patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC), significantly improving survival outcomes. However, an unmet medical need remain for patients with disease refractoriness and recurrence. Interestingly, HER2 over-expression is associated with upregulation of vascular endothelial growth factor (VEGF) in cancer cells in vitro and in vivo. Preclinical studies indicated that VEGF expression is positively regulated by HER2 signaling. In the clinical setting, HER2 over-expression correlated significantly with VEGF over- expression in samples from patients with breast cancer. There is, therefore, a biologic rationale for targeting both HER2 and VEGF pathways in patients with HER2-positive breast cancer. PURPOSE: The hypothesis that justifies this research is that the addition of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment will improve the efficacy of anti-HER2 targeted containing regimen at the metastatic setting for breast cancer.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Part 1: confirm the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast for Part 2

  Incidence of adverse events considered possibly related to Thero2-01S22 that occur any time from the first dose intake of IMP or placebo to week 6.

  Week 6

• Part 2: compare the effects of anti-HER2 targeted containing regimen with and without Thero2-01S22 in terms of Objective response rate (ORR) at week 6

  Objective response rate (ORR): Percentage of patients whose disease decreased (Partial Response, PR) and / or disappears (Complete Response, CR) after treatment, according to RECIST V1.1 criteria, Eisenhauer et al. 2009.

  Week 6

Secondary Outcomes (12)

• Part 1: determine the safety of the recommended dose of Thero2-01S22as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

  Week 6

• Part 1: determine the tolerability of the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer in terms of dose interruption

  Week 6

• Part 1: determine the tolerability of the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer in terms of palatability

  Week 6

• Part 1: determine the tolerability of the recommended dose of Thero2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer in terms of treatment duration

  From randomization to Week 6

• Part 1: characterize exposure of Thero2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast

  PK samples at day 1 of cycle 1 and cycle 2(each cycle is 21 days): before IMP or placebo intake, and at 5, 10, 15, 60, 120, 160 minutes after the intake

Study Arms (4)

Part 1: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

EXPERIMENTAL

Patients will receive Thero2-01S22 at the recommended dose and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Drug: Thero2-01S22

Part 1: Anti-HER2 targeted therapy containing regimen + Placebo

PLACEBO COMPARATOR

Patients will receive placebo and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Drug: Placebo

Part 2: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

EXPERIMENTAL

Patients will receive Thero2-01S22 at the confirmed dose and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Drug: Thero2-01S22

Part 2: Anti-HER2 targeted therapy containing regimen + Placebo

PLACEBO COMPARATOR

Patients will receive placebo and induction therapy according to local practice with a taxane (docetaxel, paclitaxel, or nab-paclitaxel) or vinorelbine for 4 to 6 cycles in combination with pertuzumab and trastuzumab

Drug: Placebo

Interventions

Thero2-01S22 DRUG

Blinded recommended dose BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Part 1: Anti-HER2 targeted therapy containing regimen + Thero2-01S22

Placebo DRUG

Blinded placebo BID for three (3) consecutive days starting the day before anti-HER2 targeted therapy containing regimen, at cycle 1 and cycle 2

Part 1: Anti-HER2 targeted therapy containing regimen + Placebo

Eligibility Criteria

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

You may qualify if:

• Women aged \> 18
• Metastatic setting of an histologically confirmed adenocarcinoma of the breast
• Performance status = 0, 1 or 2
• Metastatic disease requiring the initiation of an anti HER2 containing regimen
• First line treatment for metastatic disease
• Standard treatment including Trastuzumab and Pertuzumab in first line
• Patients for whom a 3-month life expectancy is anticipated
• Baseline LVEF value \> 50%, measured cardiac MRI or by echocardiography (Simpson's method) or MUGA scan within 12 weeks before initiation of the treatment. According to HERCEPTIN SPCs.
• Overexpression of HER2 in the invasive component of the primary tumor (3+ by ICH or 2+ with confirmation of positivity by FISH or CISH)
• Informed consent form signed

You may not qualify if:

• Patients not eligible for anti-HER2 therapy
• Patients previously treated at the metastatic setting by systemic treatment
• Serious cardiac illness or medical conditions disallowing administration of anti-HER2 therapy. According to HERCEPTIN and PERJETA SPCs.
• Known hypersensitivity to trastuzumab, pertuzumab, Thero2-01S22, murine proteins or to any of the excipients.
• Uncontrolled central nervous system metastatic lesion
• Patients who, for social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Institut de cancérologie Strasbourg Europe: lead

Study Officials

• Xavier PIVOT, MD, PhD

  Institut de cancérologie Strasbourg Europe

  STUDY CHAIR

Central Study Contacts

Valérie SARTORI

CONTACT

368767223; v.sartori@icans.eu

Manon VOEGELIN

CONTACT

368767360; promotion-rc@icans.eu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: January 26, 2023
• Study Start: May 15, 2023
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 15, 2027
• Last Updated: January 26, 2023

Record last verified: 2023-01