Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial

NCT04756505 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2020-0245NCI-2021-00434
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial is to find out the best dose, possible benefits and/or side effects of NHS-IL12 given together with bintrafusp alfa and radiation therapy in treating patients with hormone receptor positive, HER2 negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with NHS-IL12, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody avelumab and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving NHS-IL12, bintrafusp alfa, and radiation therapy may kill more tumor cells.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Hormone Receptor Positive Breast Adenocarcinoma; Metastatic Breast Carcinoma; Metastatic HER2 Negative Breast Adenocarcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Detailed information collected for each AE will include a description of the event, duration, severity, relationship to study treatment, action taken and clinical outcome. Severity of AEs will be grated according to Common Terminology Criteria for Adverse Events version .4.0.

  Up to 30 days post treatment

• Recommended phase II dose (RP2D)

  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.

  Up to 28 days

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From start of treatment until objective tumor progression or death, whichever occurs first, assessed up to 1 year

• Overall survival (OS)

  From treatment until death from any cause, assessed up to 1 year

• Percent (%) change in tumor infiltrating lymphocytes (TIL)

  Baseline up to 1 year

• Size of metastasis after treatment with both therapeutic agents with radiation (in-field) and nonirradiated (abscopal) sites

  Up to 1 years

Study Arms (1)

Treatment (bintrafusp alfa, NHS-IL12, radiation therapy)

EXPERIMENTAL

Patients receive bintrafusp alfa IV over 1 hour on days 1 and 14 and immunocytokine NHS-IL12 SC on day 14. Beginning on day 14 of cycle 1, patients undergo radiation therapy QD for up to 4 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Bintrafusp Alfa; Biological: Immunocytokine NHS-IL12; Radiation: Radiation Therapy

Interventions

Bintrafusp Alfa DRUG

Given IV

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

Treatment (bintrafusp alfa, NHS-IL12, radiation therapy)

Immunocytokine NHS-IL12 BIOLOGICAL

Given SC

Also known as: M-9241, M9241, NHS-IL-12, NHS-IL12

Treatment (bintrafusp alfa, NHS-IL12, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (bintrafusp alfa, NHS-IL12, 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
• Is age \>= 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. Men on study also must be using contraception. Women of childbearing potential (WOCBP) are women who have not been postmenopausal greater than 1 year or undergone a hysterectomy or bilateral oophorectomy
• Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. Eligible patients must have estrogen receptor (ER) and/or progesterone (PR) expression 10% or greater by immunohistochemistry (IHC). HER2 negative or nonamplified 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:
• IHC 3+ based on circumferential membrane staining that is
• Complete, intense
• ISH positive based on:
• Single-probe average HER2 copy number \>= 6.0 signals/cell
• Dual-probe HER2/CEP17 ratio \>= 2.0 with an average HER2 copy number \>= 4.0 signals/cell
• Dual-probe HER2/CEP17 ratio \>= 2.0 with an average HER2 copy number \< 4.0 signals/cell
• 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. This can include areas of metastatic disease to the bone, but one additional of the sites of metastatic disease must be amenable to biopsy
• Has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• 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

You may not qualify if:

• Anticancer treatment within 14 days before the start of trial treatment (e.g. cytoreductive therapy, radiotherapy etc.), or surgery within 4 weeks of start of trial treatment
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease =\< 3 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
• QT interval corrected for heart rate (QTc) \>= 470 ms
• Current or prior use of immunosuppressive medication within 28 days before the first dose of M7824 or NHS-IL-12, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, hypo- or hyperthyroid disease, or psoriasis not requiring systemic treatment are not excluded
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Significant acute or chronic infections including, among other:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
• Active hepatitis B virus (HBV surface antigen positive) or hepatitis C virus (HCV antibody positive and/or HCV RNA positive)
• Subjects with known active tuberculosis (history of exposure or history of positive tuberculosis test plus presence of clinical symptoms, physical or radiographic findings)
• History of allogeneic organ transplant
• History of hypersensitivity to M7824 or NHS-IL-12 or any excipient of either compound

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

bintrafusp alfa protein, human; NHS-IL12 immunocytokine; 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, MD

  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: February 11, 2021
• First Posted: February 16, 2021
• Study Start: March 7, 2021
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: December 27, 2023

Record last verified: 2023-12