A Study Evaluating the Efficacy and Safety of De Trastuzumab (T-DXd) in Combination with Immunotherapy for the Neoadjuvant Treatment of HR-positive HER2 Low-expressing Chinese Patients with Early-stage Breast Cancer

NCT06733233 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 158A01
• Study Type: interventional
• Target: 23
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, open-label, multicenter, single-arm clinical study designed to compare the efficacy and safety of neoadjuvant treatment with T-DXd in combination with an immune checkpoint inhibitor in patients with primary intermediate- to high-risk HR-positive, HER2-overexpressing early-stage breast cancer.

Conditions

Breast Cancer, Estrogen Receptor-Positive; HER2 Low Breast Cancer

Keywords

Breast cancer; immunotherapy; DS8201; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• pathologic complete remission

  3 years

Secondary Outcomes (3)

• event free survival

  3 years

• invasive disease free survival

  3 years

• overall survival

  3 years

Other Outcomes (1)

• dose-limiting toxicities

  3 years

Study Arms (1)

T-DXd combined with immune checkpoint inhibitor

EXPERIMENTAL

Drug: T-DXd combined with immune checkpoint inhibitor

Interventions

T-DXd combined with immune checkpoint inhibitor DRUG

Subjects who are eligible for the study and have signed informed consent will receive T-DXd in combination with an immune checkpoint inhibitor. The specific dosing regimen is as follows: T-DXd (5.4 mg/kg i.v. q3w) every 3 weeks for a total of 8 courses. Teraplizumab (240 mg/kg i.v. q3w), 1 course every 3 weeks for a total of 8 courses.

T-DXd combined with immune checkpoint inhibitor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults between the ages of 18 and 70 at the time of signing the informed consent form.
• An Eastern Cooperative Oncology Group (ECOG) score of 0 to 1.
• Previously untreated, operable invasive breast cancer measuring greater than 2.0 centimeters (cT2) with positive clinical lymph nodes (cN1/cN2); or clinically staged T3-T4, clinically lymph node-negative (N0) or clinically lymph node-positive (cN1/cN2) without distal metastases.
• Tumors with low levels of HER2 expression by immunohistochemistry (IHC), defined as IHC 1+ or IHC 2+ and FISH negative.
• Tumor documented as HR-positive (ER and/or PgR-positive \[ER or PgR ≥1%\] by local assessment according to ASCO-CAP guidelines).
• Patients who agree to undergo surgical treatment for breast cancer when they meet surgical criteria after neoadjuvant therapy.

You may not qualify if:

• Stage IV (metastatic) breast cancer and bilateral breast cancer
• Previous history of invasive breast cancer.
• Previous history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS)
• Other malignant tumors within 5 years, excluding cured carcinoma in situ of the cervix and non-melanoma skin cancers.

Sponsors & Collaborators

• Guangzhou Women and Children's Medical Center: lead

Related Publications (5)

• Martin M, Pandiella A, Vargas-Castrillon E, Diaz-Rodriguez E, Iglesias-Hernangomez T, Martinez Cano C, Fernandez-Cuesta I, Winkow E, Perello MF. Trastuzumab deruxtecan in breast cancer. Crit Rev Oncol Hematol. 2024 Jun;198:104355. doi: 10.1016/j.critrevonc.2024.104355. Epub 2024 Apr 16.

  PMID: 38621469 BACKGROUND

• Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. doi: 10.1056/NEJMoa2302312. Epub 2023 Mar 27.

  PMID: 36972022 BACKGROUND

• Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. doi: 10.1001/jamaoncol.2016.1897.

  PMID: 27367583 BACKGROUND

• Tarantino P, Jin Q, Tayob N, Jeselsohn RM, Schnitt SJ, Vincuilla J, Parker T, Tyekucheva S, Li T, Lin NU, Hughes ME, Weiss AC, King TA, Mittendorf EA, Curigliano G, Tolaney SM. Prognostic and Biologic Significance of ERBB2-Low Expression in Early-Stage Breast Cancer. JAMA Oncol. 2022 Aug 1;8(8):1177-1183. doi: 10.1001/jamaoncol.2022.2286.

  PMID: 35737367 BACKGROUND

• Denkert C, Seither F, Schneeweiss A, Link T, Blohmer JU, Just M, Wimberger P, Forberger A, Tesch H, Jackisch C, Schmatloch S, Reinisch M, Solomayer EF, Schmitt WD, Hanusch C, Fasching PA, Lubbe K, Solbach C, Huober J, Rhiem K, Marme F, Reimer T, Schmidt M, Sinn BV, Janni W, Stickeler E, Michel L, Stotzer O, Hahnen E, Furlanetto J, Seiler S, Nekljudova V, Untch M, Loibl S. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021 Aug;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6. Epub 2021 Jul 9.

  PMID: 34252375 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Li Jie director, Doctor

  Women and Children's Medical Center of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wang Hui jin, doctor

CONTACT

+8618312660334; wanghuijin_doc@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Thyroid and Breast Disease Center

Model Details: Subjects who are eligible for the study and have signed informed consent will receive T-DXd in combination with an immune checkpoint inhibitor. The specific dosing regimen is as follows: T-DXd (5.4 mg/kg i.v. q3w) every 3 weeks for a total of 8 courses. Teraplizumab (240 mg/kg i.v. q3w), 1 course every 3 weeks for a total of 8 courses. Upon discontinuation of the study, subjects will receive post-neoadjuvant therapy according to local clinical criteria.

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 13, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2025-01-01 to 2030-01-01