INCMGA00012 and Pelareorep for the Treatment of Metastatic Triple Negative Breast Cancer, IRENE Study

NCT04445844 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 042001NCI-2020-02940Pro2020000268P30CA072720
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 2 study to evaluate the safety and efficacy of the combination of INCMGA00012 and pelareorep and to see how well they work in treating patients with triple negative breast cancer that has spread to other parts of the body (metastatic). INCMGA00012 is a monoclonal antibody that works by attaching to the programmed cell death protein 1 (PD-1) and blocking this pathway, allowing the immune system to recognize and attack the cancer cells. Pelareorep is a type of virus called reovirus which occurs naturally and may break down cancer cells. Giving INCMGA00012 and pelareorep may slow the growth and spread of the cancer to another part of the body.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Locally Advanced Breast Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR)

  Defined as the percentage of participants having an objective response (complete response \[CR\] or partial response \[PR\]), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The ORR of the drug will be assessed according to Simon's two stage design. The estimated ORR will be compared to the response rate specified in the null hypothesis (6%) using one-sided exact binomial test at type I error 5%. 95% confidence interval (C.I.) will be also reported.

  Within 8 weeks after completion of treatment

• Incidence of adverse events

  Will be determined by the number, frequency, duration, and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0; laboratory tests and vital signs.

  Up to 2 years after completion of treatment

Secondary Outcomes (4)

• Progression free survival (PFS)

  From the start of therapy until disease progression, or death due to any cause, assessed up to 2 years after completion of treatment

• Overall survival (OS)

  From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment

• Duration of Response (DOR)

  Up to 2 years after completion of treatment

• Quality of life will be evaluated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30).

  Up to 2 years after completion of treatment

Other Outcomes (2)

• Changes in PD-L1 expression

  Pre and post-treatment

• T-cell receptor (TCR) sequencing

  Up to 2 years after completion of treatment

Study Arms (1)

Treatment (pelareorep, retifanlimab)

EXPERIMENTAL

Patients receive pelareorep IV over 60 minutes on days 1, 2, 15, and 16. Patients also receive INCMGA00012 IV over 60 minutes on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Pelareorep; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Biological: Retifanlimab

Interventions

Pelareorep BIOLOGICAL

Given IV

Also known as: PO BB0209, PO-BB0209, Reolysin, Reovirus Serotype 3, Wild-type Reovirus

Treatment (pelareorep, retifanlimab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (pelareorep, retifanlimab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (pelareorep, retifanlimab)

Retifanlimab BIOLOGICAL

Given IV

Also known as: INCMGA 0012, INCMGA-0012, INCMGA00012, INCMGA0012, MGA 012, MGA-012, MGA012

Treatment (pelareorep, retifanlimab)

Eligibility Criteria

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

You may qualify if:

• Metastatic or inoperable locally advanced, histologically documented triple negative breast cancer (TNBC) (negative expression of estrogen receptor \[ER\], progesterone receptor \[PR\] and human epidermal growth factor receptor 2 \[HER2\] immunohistochemistry \[IHC\] 0 or 1+, HER2 fluorescence in situ hybridization \[FISH\] negative if IHC 2+, per American Society of Clinical Oncology \[ASCO\] College of American Pathologists \[CAP\] guidelines)
• Pre-menopausal and post-menopausal women who have received 1-2 prior lines of systemic therapy for metastatic triple negative breast cancer. Patients must have received at least one prior line of chemotherapy
• Patients who have received adjuvant therapy for locally advanced triple negative breast cancer may be eligible for the study if they relapse with metastatic disease within 6 months since completion of neo-adjuvant/adjuvant systemic therapy. The adjuvant/neoadjuvant therapy will be considered as 1 line of therapy
• Availability of tumor specimen for determination of PD-L1 and additional biomarker studies. Patient should be willing to undergo a pre-treatment biopsy as well as a biopsy after cycle 2 to evaluate the tumor microenvironment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients who have received prior treatment with anti-PD-1 or anti-PD-L1 inhibitors are eligible for the study
• Absolute neutrophil count \>= 1,000/uL
• Platelet count \>= 100,000/uL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 2 x upper limit of normal (ULN) or =\< 3 x ULN for subjects with Gilbert's disease or liver metastases
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (=\< 5 x ULN if evidence of hepatic involvement by malignant disease)
• Estimated glomerular filtration rate (eGFR) \>= 40 mL/min/1.73m\^2
• Lactate dehydrogenase (LDH) \< 2 x ULN
• Provision of signed and dated informed consent form
• Life expectancy \>= 3 months, as determined by the investigator

You may not qualify if:

• Subjects who have received 4 or more lines prior treatment in the metastatic setting
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo, alopecia, hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, celiac disease controlled by diet alone or conditions not expected to recur in the absence of an external trigger are permitted
• History of psychiatric illness or social situations that would limit compliance with study requirements. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Known active, untreated central nervous system (CNS) metastases and/or carcinomatous meningitis except for patients with =\< 3 small (\< 0.6 cm) asymptomatic brain lesions where treatment is not indicated. Patients with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis
• Subjects previously treated with pelareorep
• Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis
• Prior allogeneic stem cell or solid organ transplantation
• Patients may not have non-oncology vaccine therapies for prevention of infectious disease (for example, seasonal live influenza vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine
• Known history of human immunodeficiency virus (HIV) or other serious immunocompromised state
• Known positive hepatitis B surface antigen undergoing anti-viral treatment and/or active hepatitis C indicated by positive quantitative hepatitis C virus (HCV) ribonucleic acid (RNA)
• Patient is pregnant or breastfeeding
• Receipt of any investigational treatment or anti-cancer therapy within 14 days of enrollment into the study
• Known hypersensitivity to the study drugs or their components
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) class III-IV within 6 months prior to their first dose of study drugs
• Prior malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 1 year prior to study entry

Sponsors & Collaborators

• Mridula George, MD: lead
• Incyte Corporation: collaborator
• Oncolytics Biotech: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

The Ohio State University Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

reolysin

Condition Hierarchy (Ancestors)

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

Study Officials

• Mridula A George

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine - Medical Oncology

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 24, 2020
• Study Start: July 13, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2)