Neoplasms

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Breast Diseases

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Interleukin-12

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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.

Bintrafusp Alfa

Immunocytokine NHS-IL12

Radiation Therapy

Meghan Karuturi, MD

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.

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of bintrafusp alfa (M7824) in combination with immunocytokine NHS-IL12 (NHS-IL-12) and radiation therapy in patients with metastatic hormone receptor positive (HR+)/HER2- breast cancer.

II. To determine the recommended phase II dose (RP2D) of NHS-IL-12 in combination with M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer.

SECONDARY OBJECTIVES:

I. To assess immunologic/molecular responses, specifically percent (%) change in tumor infiltrating lymphocytes (TIL) pre and post therapy to M7824 in combination with NHS-IL-12 and radiation therapy in patients with HR+/HER2- metastatic breast cancer.

II. To explore preliminary progression free survival (PFS) and overall survival (OS) to power future definitive trial.

III. To evaluate the in-field and abscopal effect of treatment with M7824 in combination with NHS-IL-12 and radiation therapy.

EXPLORATORY OBJECTIVES:

I. To characterize circulating immune cell populations and cytokine profiles in tumor and circulation following treatment with M7824.

II. To conduct tissue-based ribonucleic acid sequencing (RNAseq), RNA scope, whole exome sequencing (WES) targeted sequencing.

III. To correlate dosimetry to response (assessed by degree of radiation fibrosis).

IV. To evaluate the pharmacokinetics of NHS-IL-12 in combination with M7824.

OUTLINE: This is a dose-escalation study of immunocytokine NHS-IL12.

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

After completion of study treatment, patients are followed up at 30 days.

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

REINA: A Phase I Study of Radiation Enhanced IL 12-Necrosis Attraction in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients

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.

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.

PFS will be estimated for all enrolled patients and patients who receive at least one treatment using Kaplan-Meier method and compared between or among patients' characteristic groups by log-rank test. Univariate Cox regression model may be applied to assess the effect of variables of interest on PFS when appropriate.

OS will be estimated for all enrolled patients and patients who receive at least one treatment using Kaplan-Meier method and compared between or among patients' characteristic groups by log-rank test. Univariate Cox regression model may be applied to assess the effect of variables of interest on OS, when appropriate.

The % change of TIL pre and post treatment will be estimated along with 95% confidence interval. Wilcoxon signed rank test may be used to examine whether the change in TIL is different from zero.

The difference in size of metastasis measured by the longest diameters of the tumor or the shortest diameter of a lymph node by Response Evaluation Criteria in Solid Tumors, before and after treatment will be estimated for both the irradiated site (diff irradiated) and the non-irradiated site (diff non-irradiated). Will also estimate the difference between the two different sites (diff = diff non-irradiated - diff irradiated). May evaluate if diff irradiated, diff non-irradiated, and diff = diff non-irradiated - diff Irradiated are significantly different from 0 by the Wilcoxon signed rank test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial	NCT04756505	Anatomic Stage ... Hormone Recepto... Metastatic Brea... Metastatic HER2... Prognostic Stag...	Bintrafusp Alfa Immunocytokine ... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial	NCT04756505	Anatomic Stage ... Hormone Recepto... Metastatic Brea... Metastatic HER2... Prognostic Stag...	Bintrafusp Alfa Immunocytokine ... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for metastatic her2 negative breast adenocarcinoma