Radiation Therapy and M7824 in Treating Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

NCT03524170 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2017-0499NCI-2018-00961
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824) when given together with radiation therapy in treating patients with hormone receptor positive, HER2 negative breast cancer that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. M7824 is a drug that targets specific proteins on immune cells in order to activate immune responses against tumor cells. Giving M7824 together with radiation therapy may work better in treating patients with breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose (RP2D) of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer

  Will be determined by dose limiting toxicity. RP2D defined as the highest dose level with no more than 1 patient with DLT out of 6 patients that are treated.

  6 weeks after first administration of M7824

• Safety and tolerability in patients with metastatic HR+/HER2- breast cancer

  Will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. Recommended phase 2 dose (RP2D) will be determined by "3+3" design, and the recommended phase II dose is defined when 6 patients have been treated on that dose with no more than 1 dose limiting toxicity (DLT). DLT will be evaluated within 6 weeks after first administration of anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824). Detailed information collected for each adverse event (AE) will include a description of the event, duration, severity, relationship to study treatment, action taken, and clinical outcome. Severity of AEs will be graded according to the CTCAE v 4.0. Summary of AEs will include only AEs that started or worsened during the on-treatment period, the treatment-emergent AEs. However, all safety data (including those from the pre- and post-treatment periods) will be listed and those collected during the pre- and post-treatment are to be flagged.

  Start of study drug up to 30 days after study drug stopped

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Start of study drug up to 90 days after study drug stopped

• Overall survival (OS)

  Start of study drug up to 90 days after study drug stopped

• Immunologic/molecular response

  Up to 56 days

• Evaluation of the size of metastasis after treatment with M7824 with radiation (in-field) and non-irradiated (abscopal) sites

  Up to 56 days

Study Arms (1)

Treatment (M7824, radiation therapy)

EXPERIMENTAL

Patients receive M7824 IV over 1 hour every 14 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Beginning within 3 days after second dose of M7824, patients undergo radiation therapy QD for 5-10 days depending on the site of disease in the absence of disease progression or unacceptable toxicity.

Drug: Bintrafusp Alfa; Radiation: Radiation Therapy

Interventions

Bintrafusp Alfa DRUG

Given IV

Also known as: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

Treatment (M7824, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Treatment (M7824, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Is willing and able to provide written informed consent for the trial and has signed the appropriate written informed consent form, approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Highly effective contraception for both male and female subjects if the risk of conception exists. Highly effective contraception must be used 30 days prior to first trial administration, for the duration of trial treatment, and at least for 4 months after stopping trial treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.
• Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. HR defined as positive if expression greater than 10% by immunohistochemistry (IHC). HER2 negative or non-amplified is determined by the current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) criteria which are as follows: HER2 testing by IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed. HER2 is positive if: i. IHC 3+ based on circumferential membrane staining that is a. complete, intense ii. ISH positive based on: a. single-probe average HER2 copy number \>= 6.0 signals/cell. b. Dual-probe HER2/CEP17 ratio \>= 2.0 with an average HER2 copy number \>= 4.0 signals/cell c. Dual-probe HER2/CEP17 ratio \>= 2.0 with an average HER2 copy number \< 4.0 signals/cell d. Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number \>= 6.0 signals/cell.
• Has at least 2 identified sites of metastatic disease by imaging.
• Has received no more than 5 previous lines of chemotherapy and has received at least one line of therapy with an endocrine therapy or endocrine therapy combination.
• White blood cell (WBC) count \>= 3 x 10\^9/L.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L.
• Lymphocyte count \>= 0.5 x 10\^9/L.
• Platelet count \>= 100 x 10\^9/L.
• Hemoglobin (Hgb) \>= 9 g/dL.
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) level =\< 2.5 x ULN.
• Alanine aminotransferase (ALT) level =\< 2.5 x ULN.
• International normalized ratio (INR) \< 1.5.

You may not qualify if:

• Anticancer treatment within 14 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy \[with the exception of palliative radiotherapy delivered in a normal organ-sparing technique\], immune therapy, or cytokine therapy).
• Major surgery as determined by the investigator within 28 days before the start of trial treatment (prior diagnostic biopsy is permitted).
• Systemic therapy with immunosuppressive agents within 7 days before the start of treatment; or use of any investigational drug within 28 days before the start of trial treatment.
• Subjects with active central nervous system (CNS) metastases with significant neurological compromise or symptoms are excluded. Subjects with a history of treated CNS metastases (by surgery or radiation therapy), who show no evolving new neurological symptoms are eligible for the study.
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
• Significant acute or chronic infections including, among others: a. Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. b. Active hepatitis B virus (HBV) (HBV surface antigen positive) or hepatitis C virus (HCV) (HCV RNA positive). c. Subjects with known active tuberculosis (history of exposure or history of positive tuberculosis test plus presence of clinical symptoms, physical or radiographic findings).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. subjects with type I diabetes, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses 10 mg of prednisone or equivalent per day.
• Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association classification class \> II), or serious cardiac arrhythmia.
• Clinically relevant diseases (for example, inflammatory bowel disease) and /or uncontrolled medical conditions, which, in the opinion of the investigator, might impair the subject's tolerance or ability to participate in the trial.
• Vaccine administration within 4 weeks of M7824 administration. Vaccination with live vaccines while on trial is prohibited. Administration of inactivated vaccines is allowed (for example, inactivated influenza vaccines).
• Pregnancy and breast feeding.
• History of conditions associated with bleeding diatheses.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

bintrafusp alfa protein, human; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Meghan Karuturi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: May 14, 2018
• Study Start: April 30, 2018
• Primary Completion: February 10, 2022
• Study Completion: February 10, 2022
• Last Updated: March 7, 2022

Record last verified: 2022-03

Locations

US (1)