MEDI4736 and Tremelimumab in Treating Patients With Metastatic HER2 Negative Breast Cancer

NCT02536794 | Completed Phase 2 Results DMC

• 6 other identifiers: NU 15B01NCI-2015-01445ESR-14-10694D4190C00030STU00200984P30CA060553
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The main purpose of this study is to determine the anti-tumor activity of MEDI4736 in combination with tremelimumab in patients with metastatic HER2-negative breast cancer. Both MEDI4736 and tremelimumab are antibodies (proteins used by the immune system to fight infections and cancers). MEDI4736 attaches to a protein in tumors called PD-L1. It may prevent cancer growth by helping certain blood cells of the immune system get rid of the tumor. Tremelimumab stimulates (wakes up) the immune system to attack the tumor by inhibiting a protein molecule called CTLA-4 on immune cells. Combining the actions of these drugs may result in better treatment options for patients with breast cancer.

Conditions

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

  Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions: Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

• Overall Response Rate (ORR) in Patients With Triple Negative Breast Cancer (TNBC) Treated With Durvalumab in Combination With Tremelimumab

  Overall response rate is defined as the number of patients with partial response (PR), plus those with complete response (CR) using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with the following definitions: Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. TNBC = patients whose status for ER, PR and HER2 is negative

  Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and then 1 cycle = 2 weeks for up to 45 cycles

Secondary Outcomes (4)

• Toxicity in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

  Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

• Overall Survival (OS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

  Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

• Progression Free Survival (PFS) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

  Time from treatment initiation until 3 years post treatment continuation where patients were treated up to a maximum of 49 cycles where 1 cycle = 4 weeks,for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

• Clinical Benefit Rate (CBR) in Patients With Metastatic HER2 Negative Breast Cancer Treated With Durvalumab in Combination With Tremelimumab

  Up to a maximum of 49 cycles where 1 cycle = 4 weeks for the first 4 cycles and than 1 cycle =2 weeks for 45 cycles

Other Outcomes (6)

• Tumor Infiltrating Lymphocytes (TILs) Expression

  Baseline and at 2 months of treatment

• Programmed Death-ligand 1 (PD-L1) Expression

  Baseline and at 2 months of treatment

• Change in T Cell Receptor Genotype

  Baseline and at 2 months of treatment

Study Arms (1)

Treatment (MEDI4736, tremelimumab)

EXPERIMENTAL

Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.

Biological: Anti-B7H1 Monoclonal Antibody MEDI4736; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Tremelimumab

Interventions

Anti-B7H1 Monoclonal Antibody MEDI4736 BIOLOGICAL

Given IV

Also known as: MEDI4736

Treatment (MEDI4736, tremelimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (MEDI4736, tremelimumab)

Pharmacological Study OTHER

Correlative studies

Treatment (MEDI4736, tremelimumab)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Treatment (MEDI4736, tremelimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically documented (either primary or metastatic site) diagnosis of breast cancer that is HER2 non-overexpressing by immunohistochemistry, namely 0 or 1; if they have an equivocal immunohistochemistry, 2, the tumor must be non-gene amplified by fluorescence in situ hybridization (FISH) performed upon the primary tumor or metastatic lesion (ratio \< 2 and HER2 copy number \< 4); estrogen receptor (ER) positivity is defined as 1% or greater
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Patients who are ER negative must have progressed through at least one prior chemotherapy regimen in the metastatic setting or within 12 months of their last adjuvant systemic treatment; patients who are ER positive must have progressed through standard hormone therapy options and have received at least one line of chemotherapy in the metastatic setting
• Completion of prior chemotherapy systemic anticancer therapy at least 2 weeks prior to study entry
• Radiation therapy must be completed at least 2 weeks prior to study entry; radiated lesions may not serve as measurable disease unless they have been radiated over 12 months prior to enrollment
• Patients may have parenchymal brain metastases if stable (no evidence of progression) for at least 1 month after local therapy (radiation or surgery); leptomeningeal disease is excluded; must have completed any prescribed steroid taper
• Patients may have had a prior diagnosis of cancer if it has been \> 5 years since their last treatment
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 50,000/mcl
• Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) (or =\< 3 times ULN in case of liver metastasis)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\]) =\< 2.5 X institutional ULN (or =\< 5 times ULN in case of liver metastasis)
• Creatinine =\< 2 ng/ml
• Females of child-bearing potential (FOCBP) and males must agree to use 2 methods of adequate contraception prior to study entry, for the duration of study participation, and for number (#) days following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are not eligible.
• Current or prior use of immunosuppressive therapy within 2 weeks of starting investigational therapy
• Patients who are taking any herbal (alternative) medicines are NOT eligible for participation; patients must be off any such medications by the time of registration for at least 2 weeks; NOTE: Vitamin supplements are acceptable
• Patients may not have received any other investigational agents within 4 weeks prior to registration
• Prior treatment with immune therapy (including but not limited to cluster of differentiation \[CD\]137, OX40, programmed death \[PD\]-1, PD-L1 or cytotoxic T-lymphocyte antigen 4 \[CTLA4\] inhibitors)
• Prior severe infusion reaction to a monoclonal antibody
• Patients with a history of or active autoimmune disease within the past 3 years with the following exceptions:
• Vitiligo or alopecia
• Hypothyroidism on stable doses of thyroid replacement therapy
• Psoriasis not requiring systemic therapy within the past 3 years
• History of primary immunodeficiency disease or tuberculosis
• Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection) are not eligible; other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Uncontrolled pulmonary, renal, or hepatic dysfunction
• Ongoing or active infection requiring systemic treatment

Sponsors & Collaborators

• Northwestern University: lead
• MedImmune LLC: collaborator
• Avon Breast Cancer Foundation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study was closed before reaching the planned total sample size of 50 patients due to slow accrual.

Results Point of Contact

• Title: Ami Shah, MD
• Organization: Northwestern University

amishah@northwestern.edu

312 503 5488

Study Officials

• Cesar Santa-Maria, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: January 14, 2016
• Primary Completion: February 6, 2020
• Study Completion: January 22, 2021
• Last Updated: May 17, 2022
• Results First Posted: April 23, 2021

Record last verified: 2022-04

Locations

US (2)