A Study Of Pembrolizumab In Combination With Trastuzumab-DM1

NCT03032107 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-492
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of drugs as a possible treatment for metastatic breast cancer. The interventions involved in this study are:

• Pembrolizumab
• Trastuzumab emtansine (also called T-DM1)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  The number and type of DLTs as defined in the protocol that occur during the first 21 days of treatment and all maximum grade of all treatment-related adverse events using CTCAE v4.0 will be used to identify a safe and tolerable dose

  21 days

Secondary Outcomes (5)

• Objective Response Rate

  2 years

• Progression Free Survival

  2 years

• Duration Of Response

  2 years

• Disease Control Rate

  18 weeks

• Overall Survival Rate

  5 years

Study Arms (1)

Pembrolizumab Combine With Trastuzumab Emtansine

EXPERIMENTAL

* Pembrolizumab will be administered intravenousely in clinic on day 1 of each 3-week cycle * Pembrolizumab will be administered prior to T-DM1 administration * Pembrolizumab will be given at a predetermine dose * T-DM1 will be administered intravenousely in clinic on day 1 of each 3-week cycle * T-DM1 will be given at a predetermine dose

Drug: T-DM1; Drug: Pembrolizumab

Interventions

T-DM1 DRUG

-T-DM1 will be administered intravenousely in clinic on day 1 of each 3-week cycle

Also known as: Trastuzumab emtansine

Pembrolizumab Combine With Trastuzumab Emtansine

Pembrolizumab DRUG

-Pembrolizumab will be administered intravenousely in clinic on day 1 of each 3-week cycle

Also known as: Keytruda

Pembrolizumab Combine With Trastuzumab Emtansine

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Either the primary tumor and/or the metastasis must have been tested for ER, PR and HER2. Patient must have HER2+ breast cancer per ASCO CAP guidelines 2013.
• Prior chemotherapy:
• History of prior therapy with trastuzumab and a taxane, separately or in combination, is required.
• Patients must have either received one line of prior therapy for metastatic breast cancer, or have developed a disease recurrence during or within 6 months after completing adjuvant therapy.
• No prior treatment with T-DM1 is allowed.
• Last dose of chemotherapy must be at least 21 days prior to registration.
• Prior biologic therapy:
• Patients must have discontinued all biologic or investigational therapy at least 21 days before registration.
• Prior radiation therapy:
• Patients may have received prior radiation therapy in either the metastatic or early-stage setting.
• Radiation therapy must be completed at least 14 days prior to registration.
• In the dose de-escalation cohort: Subjects must have evaluable disease. In the expansion cohort: Subjects must have at least one lesion that is not within a previously radiated field that is measurable on computerized tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version 1.1. Bone lesions are not considered measurable by definition.
• Age is ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

You may not qualify if:

• The subject has received another investigational agent within 21 days of the first dose of study drug.
• The subject has received prior pembrolizumab or any other anti-PD-1 , anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab.
• Pre-existing neuropathy greater than or equal to grade 2.
• Hypersensitivity to pembrolizumab or T-DM1 or any of their excipients.
• The subject has any history or evidence of active, non-infectious pneumonitis or interstitial lung disease.
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have completed treatment at least one month prior to trial therapy initiation, are neurologically stable with an absence of new neurological symptoms for at least 4 weeks prior to study entry, and have recovered from effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before the first study drug. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician.
• Known carcinomatous meningitis.
• The subject has an uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see Appendix B), active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, chronic liver or renal disease, or severe malnutrition.
• Concurrent use of potent CYP3A4 inhibitors (see Appendix C), such as ketoconazole and erythromycin, should be avoided during the study treatment with T-DM1.
• Active infection requiring intravenous antibiotics at cycle 1 day 1.
• Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
• The subject has a medical condition that requires chronic systemic steroid therapy or any other form of immunosuppressive medication including disease modifiying agents, or has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• The subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
• The participant is positive for Hepatitis B surface antigen, or Hepatitis C RNA.
• Known HIV-positive participants. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections with bone marrow suppressive therapy, i.e. nab-paclitaxel. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET 3rd, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. J Immunother Cancer. 2022 Oct;10(10):e005119. doi: 10.1136/jitc-2022-005119.

  PMID: 36252998 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-3800

Study Officials

• Sara Tolaney, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 26, 2017
• Study Start: February 17, 2017
• Primary Completion: October 29, 2020
• Study Completion: December 5, 2024
• Last Updated: January 27, 2025
• Results First Posted: December 2, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)