Neoadjuvant Her2-targeted Therapy and Immunotherapy With Pembrolizumab (neoHIP)
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- HER2-positive Breast Cancer
- Sponsor
- University of Texas Southwestern Medical Center
- Enrollment
- 138
- Locations
- 5
- Primary Endpoint
- Pathological Complete Response (pCR)
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
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.
Detailed Description
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. Patients will be randomized to either Arm A: THP (trastuzumab, pertuzumab and weekly paclitaxel), Arm B: THP-pembrolizumab (trastuzumab, pertuzumab, pembrolizumab) and weekly paclitaxel) or Arm C: TH-pembrolizumab (trastuzumab, pembrolizumab and weekly paclitaxel). Patients will be stratified according to hormone receptor status and lymph node status. All patients will be treated weekly every three weeks for four cycles (only paclitaxel will be administered weekly) and then undergo breast surgery. Arm A patients will be regarded as the reference group.
Investigators
Heather McArthur
ASSOCIATE PROFESSOR
University of Texas Southwestern Medical Center
Eligibility Criteria
Inclusion Criteria
- •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
- •Have adequate organ function as defined by the following parameters. Specimens must be collected within 7 days prior to the start of study treatment.
Exclusion Criteria
- •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.
Arms & Interventions
Arm A: THP
Arm A: Paclitaxel weekly x12 + Trastuzumab + Pertuzumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Paclitaxel
Arm A: THP
Arm A: Paclitaxel weekly x12 + Trastuzumab + Pertuzumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Trastuzumab
Arm A: THP
Arm A: Paclitaxel weekly x12 + Trastuzumab + Pertuzumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Pertuzumab
Arm B: THP-Pembrolizumab
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.
Intervention: Paclitaxel
Arm B: THP-Pembrolizumab
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.
Intervention: Trastuzumab
Arm B: THP-Pembrolizumab
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.
Intervention: Pertuzumab
Arm B: THP-Pembrolizumab
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.
Intervention: Pembrolizumab
Arm C: TH-Pembrolizumab
Arm C: Paclitaxel weekly x12 + Trastuzumab + Pembrolizumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Paclitaxel
Arm C: TH-Pembrolizumab
Arm C: Paclitaxel weekly x12 + Trastuzumab + Pembrolizumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Trastuzumab
Arm C: TH-Pembrolizumab
Arm C: Paclitaxel weekly x12 + Trastuzumab + Pembrolizumab All subjects may receive standard of care systemic therapy after surgery per their treating physician's discretion.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Pathological Complete Response (pCR)
Time Frame: 16 weeks from randomization
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.
Secondary Outcomes
- Symptomatic Cardiac Events and Asymptomatic LVEF Events(36 months from randomization)
- 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)
- Invasive Disease-free Survival (IDFS)(33 months from surgery)
- Overall Survival(36 months from randomization)
- AEs and SAEs(20 weeks from treatment initiation)