Combination Study of SV-BR-1-GM With Retifanlimab

NCT03328026 | Completed Phase 1 FDA Drug

• 1 other identifier: BRI-ROL-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 14

Brief Summary

This is an open-label, phase I/II double arm study of the SV-BR-1-GM regimen in combination with retifanlimab in patients with metastatic or locally recurrent breast cancer who have failed standard therapy. Patients will receive the SV-BR-1-GM regimen with combination immunotherapy. There will be an initial evaluation of the combination of the SV-BR-1-GM regimen with retifanlimab every 3 weeks. If this is found to be safe and well tolerated in a cohort of at least 12 patients (dose-limiting toxicities (DLTs) in less than 30% of the patients evaluated), then an expansion cohort of up to 24 patients will be treated with that combination. These will be randomized to two regimens differing in the timing of checkpoint inhibitor administration.

Conditions

Breast Neoplasm; Breast Cancer Metastatic; Breast Cancer; Metastatic Breast Cancer

Keywords

Breast Cancer; Metastatic Breast Cancer; MBC; Immunotherapy; Cancer Vaccine

Outcome Measures

Primary Outcomes (3)

• Evaluate the Adverse Events (AEs), including Serious Adverse Events (SAEs), that occur in patients treated with SV-BR-1-GM administered in combination with INCMGA00012 (retifanlimab) [Safety]

  To evaluate the safety of SV-BR-1-GM as assessed by: o Adverse Events (AEs), including Serious Adverse Events (SAEs)

  Through study completion, an average of 1 year

• Evaluate the Proportion of Patients with Abnormalities in Safety Laboratory Parameters that occur in patients treated with SV-BR-1-GM administered in combination with INCMGA00012 (retifanlimab) [Safety]

  To evaluate the safety of SV-BR-1-GM as assessed by: o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters

  Through study completion, an average of 1 year

• Evaluate changes in the electrocardiogram QT interval that occur in patients treated with SV-BR-1-GM administered in combination with INCMGA00012 (retifanlimab)[Safety]

  To evaluate the safety of SV-BR-1-GM as assessed by: o Electrocardiograms (ECG) with measurement of the QT interval

  Through study completion, an average of 1 year

Secondary Outcomes (3)

• Evaluate the tumor response to SV-BR-1-GM (ORR) when administered in combination with INCMGA00012 (retifanlimab)

  Through study completion, an average of 1 year

• Evaluate the tumor response to SV-BR-1-GM (Non-progression) when administered in combination with INCMGA00012 (retifanlimab)

  Through study completion, an average of 1 year

• Evaluate the tumor response to SV-BR-1-GM (Durability) when administered in combination with INCMGA00012 (retifanlimab)

  Through study completion, an average of 1 year

Study Arms (2)

SV-BR-1-GM, retifanlimab combination original sequence

EXPERIMENTAL

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab with cycles every 3 weeks

Biological: SV-BR-1-GM; Drug: Low dose cyclophosphamide; Drug: Interferon Inoculation; Drug: retifanlimab

SV-BR-1-GM, retifanlimab combination alternative sequence

EXPERIMENTAL

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab as follows: Cycle 1: SV-BR-1-GM only Cycle 2: resume retifanlimab on Day 2±1 Cycle 3 and beyond: retifanlimab can be administered on Day -2, Day 0, 1, 2, or 3.

Biological: SV-BR-1-GM; Drug: Low dose cyclophosphamide; Drug: Interferon Inoculation; Drug: retifanlimab

Interventions

Low dose cyclophosphamide DRUG

Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.

Also known as: Cytoxan

SV-BR-1-GM, retifanlimab combination alternative sequence; SV-BR-1-GM, retifanlimab combination original sequence

SV-BR-1-GM BIOLOGICAL

SV-BR-1-GM inoculation intradermally at 4 sites.

SV-BR-1-GM, retifanlimab combination alternative sequence; SV-BR-1-GM, retifanlimab combination original sequence

Interferon Inoculation DRUG

Post-inoculation low dose Interferon into the vaccination sites \~2 days after SV-BR-1-GM inoculation.

SV-BR-1-GM, retifanlimab combination alternative sequence; SV-BR-1-GM, retifanlimab combination original sequence

retifanlimab DRUG

retifanlimab 375mg administered as an intravenous infusion over 30-60 minutes every 3 weeks per randomization

Also known as: INCMGA00012

SV-BR-1-GM, retifanlimab combination alternative sequence; SV-BR-1-GM, retifanlimab combination original sequence

Eligibility Criteria

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

You may qualify if:

• Have histological confirmation of breast cancer with recurrent and/or metastatic lesions, as per the investigational site, and have failed prior therapy.
• Patients with persistent disease and local recurrence must not be amenable to local treatment.
• For patients with metastatic disease:
• Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER) or progesterone receptor (PR) positive tumors: must be refractory to hormonal therapy (e.g., aromatase inhibitor, tamoxifen or fluvestrant) and previously treated with at least 2 regimens including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab).
• HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fluvestrant) and previously treated with at least 2 chemotherapy containing regimens. (e.g. CDK4/6 inhibitor, PIK3CA inhibitor, etc)
• HER2 positive and ER and PR negative tumors: must have failed at least 2 regimens including at least two anti-HER2 agents (e.g., trastuzumab and pertuzumab).
• Triple Negative tumors: Must have exhausted other available therapies including prior treatment with a taxane and carboplatin.
• Patients with new or progressive breast cancer metastatic to the brain will be eligible provided:
• The brain metastases must be clinically stable (without evidence of progressive disease by imaging) for at least 4 weeks prior to first dose
• Must have received prior radiation therapy for brain metastases or be ineligible for radiation therapy
• There is no need for steroids and patients have not had steroids for at least 2 weeks
• No individual tumor size is \>50 mm
• Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
• If surgically debulked, must be healed from surgery and at least 3 weeks have elapsed since general anesthesia
• Patients consent to MRI studies at 3-4 week intervals until evidence of tumor regression on at least 2 imaging studies. In no case, will the interval between MRI studies be longer than 3 months. MRI studies may be introduced at any time should the patients develop new or clearly worsening symptoms and/or introduction of steroids

You may not qualify if:

• Concurrent or recent chemotherapy, immunotherapy (except the SV-BR-1-GM regimen), or general anesthesia/major surgery within 21 days. Patients must have recovered from all known or expected toxicities from previous systemic treatment and passed a treatment-free "washout" period of 3 weeks before starting this program (8 weeks for patients receiving nitrosourea or mitomycin). Prior immune related toxicity should not have exceeded Grade 2 (with exception of endocrinopathy).
• Radiotherapy within 14 days of first dose of study treatment with the following caveats:
• days for pelvic radiotherapy.
• weeks for brain metastases
• months for thoracic region radiotherapy that is \> 30 Gy in 2 Gy fractions.
• Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
• History of clinical hypersensitivity to the designated combination immunotherapy, GM-CSF, Interferon, yeast, beef, or to any components used in the preparation of SV-BR-1-GM.
• History of clinical hypersensitivity to any of the immunotherapies proposed for combination treatment or their excipients.
• Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (e.g., antihistamines and corticosteroids) or known allergy or hypersensitivity to any component of retifanlimab or formulation components.
• Serum creatinine OR Measured or calculated Creatinine Clearance (CrCl) (GFR can also be used in place of creatinine or CrCl) \>1.5 × ULN OR \<30 mL/min for participants with creatinine levels \>1.5 × institutional ULN.
• Absolute granulocyte count \<1000; platelets \<100,000; hemoglobin ≤ 8 g/L.
• INR or PT or aPTT \> 1.5 × ULN, unless the participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. Note: See the restricted medications list in protocol section 5.9. If an alternative cannot be found, the participant cannot be enrolled.
• Receiving any medication listed in the prohibited medication (section 5.10 of the protocol).
• Proteinuria \>1+ on urinalysis or \>1 gm/24hr.
• History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful. Screening corrected QT interval (QTc) interval \>480 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is \>480 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is \<480 milliseconds.

Sponsors & Collaborators

• LumaBridge: collaborator
• BriaCell Therapeutics Corporation: lead

Study Sites (14)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami/Sylvester at Plantation

Plantation, Florida, 33324, United States

Location

Carle Cancer Institute

Urbana, Illinois, 61801, United States

Location

Cancer Center of Kansas (CCK)

Wichita, Kansas, 67214, United States

Location

The Center for Cancer and Blood Disorders a division of American Oncology Partners MD

Bethesda, Maryland, 20817, United States

Location

St Vincent-Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Overlook Medical Center Oncology Research, Atlantic Health System

Summit, New Jersey, 07901, United States

Location

Manhattan Hematology Oncology Associates (MHOA)

Manhattan, New York, 10016, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Tranquil Clinical Research

Webster, Texas, 77598, United States

Location

Hematology-Oncology Associates of Fredericksburg, Inc

Fredericksburg, Virginia, 22408, United States

Location

Related Links

• Sponsor Website
• CRO Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• George E Peoples, MD, FACS

  LumaBridge LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: November 1, 2017
• Study Start: March 16, 2018
• Primary Completion: March 24, 2026
• Study Completion: March 24, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)