Neoadjuvant Her2-targeted Therapy and Immunotherapy With Pembrolizumab [IIT2018-04-MCARTHUR-NEOHP]

NCT03747120 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: STU-2021-0558
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 5

Brief Summary

A phase 2 open-label, randomized, multi-center trial to evaluate the efficacy and safety of neoadjuvant trastuzumab, pertuzumab and weekly paclitaxel (THP) as compared to neoadjuvant trastuzumab, pertuzumab, pembrolizumab and weekly paclitaxel (THP-pembrolizumab), or neoadjuvant trastuzumab, pembrolizumab and weekly paclitaxel (TH-pembrolizumab ) in chemo naive patients with invasive human epidermal growth factor receptor 2 (HER2) positive breast cancer whose primary tumors are \> 2 cm and/or clinically lymph node positive. Treatment will be followed by standard of care breast surgery and physician's choice adjuvant therapy per standard of care.

Conditions

HER2-positive Breast Cancer; Breast Cancer

Keywords

her2-positive breast cancer; Breast Cancer; Pembrolizumab; Immunotherapy; Neoadjuvant her2 targeted therapy; Trastuzumab; Pertuzumab; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  Proportion of subjects without residual invasive cancer in the breast and axilla from randomization to definitive surgery. \- Residual invasive cancer defined based on hematoxylin and eosin evaluation of complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by pathologist assessment.

  16 weeks from randomization

Secondary Outcomes (9)

• Pathological Complete Invasive and in Situ Response Rate (Breast and Axilla)

  16 weeks from randomization

• Pathological Complete Response Rate (pCR) in Breast Only

  16 weeks from randomization

• Residual Cancer Burden (RCB)

  16 weeks from randomization

• Breast Conserving Surgery Rate

  16 weeks from randomization

• Event Free Survival

  36 months from randomization

Study Arms (3)

Arm A: THP

ACTIVE COMPARATOR

Arm A: Paclitaxel weekly x12 + Trastuzumab + Pertuzumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab

Arm B: THP-Pembrolizumab

EXPERIMENTAL

Arm B: Paclitaxel weekly x12 + Trastuzumab + Pertuzumab + Pembrolizumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Pembrolizumab

Arm C: TH-Pembrolizumab

EXPERIMENTAL

Arm C: Paclitaxel weekly x12 + Trastuzumab + Pembrolizumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Pembrolizumab

Interventions

Paclitaxel DRUG

All subjects will receive Paclitaxel weekly for 12 weeks

Also known as: Taxol

Arm A: THP; Arm B: THP-Pembrolizumab; Arm C: TH-Pembrolizumab

Trastuzumab DRUG

All subjects will receive Trastuzumab every 3 weeks

Also known as: Herceptin

Arm A: THP; Arm B: THP-Pembrolizumab; Arm C: TH-Pembrolizumab

Pertuzumab DRUG

Arm A and Arm B subjects will receive Pertuzumab every 3 weeks

Also known as: Perjeta

Arm A: THP; Arm B: THP-Pembrolizumab

Pembrolizumab DRUG

Arm B and Arm C subjects will receive Pembrolizumab every 3 weeks

Also known as: Keytruda

Arm B: THP-Pembrolizumab; Arm C: TH-Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male/female patients with histologically confirmed invasive HER2-positive (by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines) unilateral breast cancer
• Have previously untreated non-metastaic (M0), cT2-4N0 or cT1-4N1-3 (biopsies of clinically suspicious lymph nodes to confirm nodal status is encouraged).
• Multifocal/centric disease is permitted if all suspicious foci have been biopsied and are consistent with HER2-positive (by ASCO/CAP guidelines) invasive breast cancer
• Be a male or female subject 18 years of age on the day of signing informed consent
• Male Participants: A male participant must agree to use a contraception as detailed in Appendix C of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period.
• Female Participants: A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the treatment period and for at least 6 months after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Provides adequate archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate organ function as defined by the following parameters. Specimens must be collected within 7 days prior to the start of study treatment.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
• Renal Creatinine (≤1.5 × ULN OR) OR Measured or calculated(b) creatinine clearance (≥30 mL/min for participant with creatinine levels) (GFR can also be used in place of creatinine or CrCl) (\>1.5 × institutional ULN)
• Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-PD-1 (programmed death protein 1), anti-PD-L1 (Programmed death-ligand 1), or anti PD L2 (Programmed death-ligand 2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active systemic treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has a known active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (i.d. HCV RNA \[qualitative\] is detected) infection.
• Has a known history of active TB (Bacillus Tuberculosis).

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Breast Cancer Research Foundation: collaborator

Study Sites (5)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

New Mexico Cancer Center

Albuquerque, New Mexico, 87109, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75006-7541, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; pertuzumab; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Heather McArthur, Professor IM-Hem Onc
• Organization: University of Texas Southwestern Medical Center

heather.mcarthur@utsouthwestern.edu

214-645-9380

Study Officials

• Heather McArthur, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Model Details: 1:1:1 randomization

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 20, 2018
• Study Start: January 25, 2019
• Primary Completion: November 8, 2024
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 27, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-06

Locations

US (5)