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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03328026
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : May 3, 2023
Sponsor:
Collaborator:
LumaBridge
Information provided by (Responsible Party):
BriaCell Therapeutics Corporation

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Breast Neoplasm Metastatic Breast Cancer Breast Cancer Metastatic Biological: SV-BR-1-GM Drug: Low dose cyclophosphamide Drug: Interferon Inoculation Drug: retifanlimab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the SV-BR-1-GM Regimen in Metastatic or Locally Recurrent Breast Cancer Patients in Combination With Retifanlimab
Actual Study Start Date : March 16, 2018
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SV-BR-1-GM, retifanlimab combination original sequence
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
SV-BR-1-GM inoculation intradermally at 4 sites.

Drug: Low dose cyclophosphamide
Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.
Other Name: Cytoxan

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

Drug: retifanlimab
retifanlimab 375mg administered as an intravenous infusion over 30-60 minutes every 3 weeks per randomization
Other Name: INCMGA00012

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

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

Drug: Low dose cyclophosphamide
Pretreatment with low dose cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation.
Other Name: Cytoxan

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

Drug: retifanlimab
retifanlimab 375mg administered as an intravenous infusion over 30-60 minutes every 3 weeks per randomization
Other Name: INCMGA00012




Primary Outcome Measures :
  1. 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] [ Time Frame: Through study completion, an average of 1 year ]

    To evaluate the safety of SV-BR-1-GM as assessed by:

    o Adverse Events (AEs), including Serious Adverse Events (SAEs)


  2. 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] [ Time Frame: Through study completion, an average of 1 year ]

    To evaluate the safety of SV-BR-1-GM as assessed by:

    o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters


  3. Evaluate changes in the electrocardiogram QT interval that occur in patients treated with SV-BR-1-GM administered in combination with INCMGA00012 (retifanlimab)[Safety] [ Time Frame: Through study completion, an average of 1 year ]

    To evaluate the safety of SV-BR-1-GM as assessed by:

    o Electrocardiograms (ECG) with measurement of the QT interval



Secondary Outcome Measures :
  1. Evaluate the tumor response to SV-BR-1-GM (ORR) when administered in combination with INCMGA00012 (retifanlimab) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per RECIST 1.1


  2. Evaluate the tumor response to SV-BR-1-GM (Non-progression) when administered in combination with INCMGA00012 (retifanlimab) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Non-progressive rate, defined as CR, PR or stable disease (SD) per iRECIST


  3. Evaluate the tumor response to SV-BR-1-GM (Durability) when administered in combination with INCMGA00012 (retifanlimab) [ Time Frame: Through study completion, an average of 1 year ]

    Tumor response as assessed by:

    o Duration of response




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Have histological confirmation of breast cancer with recurrent and/or metastatic lesions, as per the investigational site, and have failed prior therapy.

2. Patients with persistent disease and local recurrence must not be amenable to local treatment.

3. For patients with metastatic disease:

  1. 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).
  2. 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.
  3. 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).
  4. 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:

a. The brain metastases must be clinically stable (without evidence of progressive disease by imaging) for at least 4 weeks prior to first dose b. Must have received prior radiation therapy for brain metastases or be ineligible for radiation therapy c. There is no need for steroids and patients have not had steroids for at least 2 weeks d. No individual tumor size is >50 mm e. Tumor is not impinging on Middle Cerebral Artery/speech-motor strip f. If surgically debulked, must be healed from surgery and at least 3 weeks have elapsed since general anesthesia g. 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

4. Be 18 years of age or older and female 5. Have expected survival of at least 4 months 6. Have adequate performance status (ECOG 0-1) Patients with ECOG of 2 may be admitted only with Sponsor approval.

7. Have provided written informed consent 8. For the Expansion cohorts, patients must also either have:

  1. Grade I (well-differentiated) or grade II (moderately differentiated) tumor histology based on prior pathological findings OR
  2. Match the SV-BR-1-GM cell line at least at one HLA type (HLA-A*24:02, B*35:08, B*55:01, C*01:02, C*04:01, DRB3*01:01, DRB3*02:02, DRB1*11:04 or DRB1*13:03)

    Exclusion Criteria:

    1. 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 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).
    2. Radiotherapy within 14 days of first dose of study treatment with the following caveats:

      a. 28 days for pelvic radiotherapy. b. 8 weeks for brain metastases c. 6 months for thoracic region radiotherapy that is > 30 Gy in 2 Gy fractions.

    3. Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support). Endocrinopathy, if well-managed, is not exclusionary and should be discussed with medical monitor.
    4. Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
    5. 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.
    6. History of clinical hypersensitivity to any of the immunotherapies proposed for combination treatment or their excipients.
    7. 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.
    8. 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.
    9. Absolute granulocyte count <1000; platelets <100,000; hemoglobin ≤ 9 g/L.
    10. Bilirubin ≥ 1.5 × ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >2x ULN. For patients with hepatic metastases, ALT/AST >5x ULN is exclusionary.
    11. 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.
    12. Receiving any medication listed in the prohibited medication (section 5.10 of the protocol).
    13. Proteinuria >1+ on urinalysis or >1 gm/24hr.
    14. 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.

    16. Left ventricular ejection fraction (LVEF as determined by cardiac echo or MUGA scan) below the normal limits of the institutions' specific testing range.

    17. New York Heart Association stage 3 or 4 cardiac disease. 18. A pericardial effusion of moderate severity or worse. 19. Symptomatic pleural effusion or ascites. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.

    20. Any woman of childbearing potential (i.e., has had a menstrual cycle within the past year and has not been surgically sterilized), unless she: agrees to take appropriate precautions to avoid becoming pregnant during the study (with at least 99% certainty, see Appendix A for permitted methods) and has a negative serum pregnancy test within 7 days prior to starting treatment.

    21. Men must have been sterile or, if they were potentially fertile/reproductively competent, should take appropriate precautions to avoid fathering a child for the duration of the study.

    22. Women who are pregnant or nursing. 23. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent.

    24. Patients who are HIV positive (by self-report) or have clinical or laboratory features indicative of AIDS.

    25. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

    25. Has had an allogeneic tissue/solid organ transplant. 26. Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.

    27. Patients with a history of colitis. 28. Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.

    29. Known active HBA, HBV, or HCV infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, anti-HCV, anti-HBc IgG or IgM, or HBsAg (in the absence of prior immunization).

    30. Active infections requiring systemic therapy.

a. All antibiotic therapy within 28 days of initiating treatment must be recorded 31. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). 32. Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator in consultation with the medical monitor.

33. Has received a live vaccine within 28 days of the planned start of study drug. Note: examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live-attenuated vaccines and are not allowed.

34. Patients may not be on a concurrent clinical trial, unless approved by the Investigator.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03328026


Contacts
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Contact: Jane Hart, MBA 210-268-6121 jhart@lumabridge.com
Contact: Michelle Reeves, CTA 210-722-4936 mreeves@lumabridge.com

Locations
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United States, California
Hoag Memorial Hospital Presbyterian Recruiting
Newport Beach, California, United States, 92663
Contact: Marilyn Wright    949-764-6752    Marilyn.Wright@hoag.org   
Contact: Ana Navarrete    949-764-6753    Ana.Navarrete@hoag.org   
Principal Investigator: Chaitali S Nangia, MD         
St. Joseph Heritage Healthcare Recruiting
Santa Rosa, California, United States, 95403
Contact: Kimberly Young, BS, RN, CCRC    707-521-3830    kimberly.young@stjoe.org   
Contact: Charity Behrend    707-521-3829    Charity.Behrend@Providence.org   
Principal Investigator: Jarrod P Holmes, M.D.         
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact: Emily R Huffman, CCRC    904-953-7610    huffman.emily@mayo.edu   
Principal Investigator: Saranya Chumsri, MD         
University of Miami/Sylvester at Plantation Recruiting
Plantation, Florida, United States, 33324
Contact: Deborah M Conte, CCRC    954-210-1171    dmc238@med.miami.edu   
Principal Investigator: Carmen J Calfa, MD         
United States, Illinois
Carle Cancer Institute Recruiting
Urbana, Illinois, United States, 61801
Contact: Christine Rogers, CCRC    217-383-3394    christine.rogers@carle.com   
Contact: Jocelyn Harseim       Jocelyn.Harseim@Carle.com   
Principal Investigator: Kendrith Rowland, MD         
United States, Kansas
Cancer Center of Kansas (CCK) Recruiting
Wichita, Kansas, United States, 67214
Contact: Pat Stone, RN    316-613-4313    Pat.stone@cancercenterofkansas.com   
Contact: Shaker Dakhil, MD    (316) 262-4467    John.Taylor@cancercenterofkansas.com   
Principal Investigator: Shaker Dakhil, MD         
United States, Maryland
The Center for Cancer and Blood Disorders a division of American Oncology Partners MD Recruiting
Bethesda, Maryland, United States, 20817
Contact: Jenelle Larkin, CRC    301-571-2016    Jenelle.Larkin@aoncology.com   
Contact: Natalie Bongiorno, RN, MSHS    301.571.2016    Natalie.Bongiorno@aoncology.com   
Principal Investigator: Ralph Boccia, MD         
United States, New Jersey
Overlook Medical Center Oncology Research, Atlantic Health System Recruiting
Summit, New Jersey, United States, 07901
Contact: Christopher Buck    201-572-9943    christopher.buck@atlantichealth.org   
Contact: Christine Koranyi    (862) 881-9131    christine.koranyi@atlantichealth.org   
Principal Investigator: Bonni Guerin, MD         
United States, New York
Manhattan Hematology Oncology Associates (MHOA) Recruiting
Manhattan, New York, United States, 10016
Contact: Patricia Rose, RN    212-689-6791    clinicaltrials@mhony.com   
Principal Investigator: Alec Goldenberg, MD         
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Akhil Valiyil, CRC    972-566-3061    avaliyil@marycrowley.org   
Contact: Minal Barve, MD    972-566-3000    Referral@MaryCrowley.org   
Principal Investigator: Minal Barve, MD         
Tranquil Clinical Research Recruiting
Webster, Texas, United States, 77598
Contact: Francis O Oyih, CRC    346-435-9512    franciso@TranquilityResearch.com   
Contact: John Knecht, MD    832 748-1074    ResearchParticipation@TranquilConsulting.com   
Principal Investigator: John Knecht, MD         
United States, Virginia
Hematology-Oncology Associates of Fredericksburg, Inc Recruiting
Fredericksburg, Virginia, United States, 22408
Contact: Ashley Lawrence, RN    540-371-0079    alawrence@hoafredericksburg.com   
Contact: Amber Spurley    540-371-0079    research@hoafredericksburg.com   
Principal Investigator: Christopher N. Vaughn, MD         
Sponsors and Collaborators
BriaCell Therapeutics Corporation
LumaBridge
Investigators
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Study Director: George E Peoples, MD, FACS LumaBridge LLC
Additional Information:
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Responsible Party: BriaCell Therapeutics Corporation
ClinicalTrials.gov Identifier: NCT03328026    
Other Study ID Numbers: BRI-ROL-001
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by BriaCell Therapeutics Corporation:
Breast Cancer
Metastatic Breast Cancer
MBC
Immunotherapy
Cancer Vaccine
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Interferons
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antiviral Agents
Anti-Infective Agents