Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer

• ClinicalTrials.gov Identifier: NCT02593227
• Recruitment Status: Completed
• First Posted: November 1, 2015
• Last Update Posted: July 19, 2021
• Sponsor: Marker Therapeutics, Inc.
• Information provided by (Responsible Party): Marker Therapeutics, Inc.

Tracking Information

• First Submitted Date: October 27, 2015
• First Posted Date: November 1, 2015
• Last Update Posted Date: July 19, 2021
• Actual Study Start Date: April 2016
• Actual Primary Completion Date: July 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 30, 2015)

Immune response [ Time Frame: 3 years ]

Emergence of B and T cell immunity targeting the folate receptor alpha

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 25, 2016)

• Folate receptor alpha expression [ Time Frame: Baseline ]
  To determine FRα expression status of primary tumors
• Relapse Free Survival [ Time Frame: 3 years ]
  RFS in relation to FR specific immune response
• Safety and tolerability (treatment emergent adverse events and injection site reactions) [ Time Frame: 3 years ]
  Incidence of treatment emergent adverse events and injection site reactions

Original Secondary Outcome Measures (submitted: October 30, 2015)

• Folate receptor alpha expression [ Time Frame: Baseline ]
  To determine FRα expression status of primary tumors
• Relapse Free Survival [ Time Frame: 3 years ]
  RFS in relation to FR specific immune response
• Objective response rate [ Time Frame: 3 years ]
  ORR in the subset of patients with residual disease
• Safety and tolerability (treatment emergent adverse events and injection site reactions) [ Time Frame: 3 years ]
  Incidence of treatment emergent adverse events and injection site reactions

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer
• Official Title: A Randomized Multicenter Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of Vaccination With Folate Receptor Alpha Peptides With GM-CSF in Patients With Triple Negative Breast Cancer Defined as Primary Tumor That is Her2-neu and Low (< 10%) ER/PR Nuclear Staining
• Brief Summary: This Phase II trial evaluates the safety and immunogenicity of two doses of the Folate Receptor Alpha (FRα) peptide vaccine mixed with GM-CSF as a vaccine adjuvant, with or without a immune priming with cyclophosphamide, as a consolidation therapy after neoadjuvant or adjuvant treatment of patients with Stage IIb-III triple negative breast cancer (TNBC).

Detailed Description

Triple negative breast cancers (TNBCs) occur in approximately 20-25% of all patients with breast cancer and are associated with a poor prognosis. Patients with TNBCs derive no benefit from targeted therapies. Excluding those patients who demonstrate a pathologic complete response following neoadjuvant chemotherapy, which is a minor fraction (i.e. 15%), overall survival is only 45% at 7 years.

Following standard of care, there are windows of opportunity to further and safely treat patients to prevent recurrence. Stimulating the immune system to produce T cells immunity specific for tumor antigens may significantly delay recurrence and cure patients.

The proposed vaccine is intended to induce T cells to survey for the reemergence of TNBCs and to prevent recurrence in the adjuvant setting. The vaccine strategy is antigen-specific and targets the Folate Receptor Alpha (FRα). FRα is an ideal target because of its limited expression in the healthy tissues and it high expression in 86% of TNBCs. Studies have shown that it is a biologically important marker that is associated with poorer clinical outcome and is retained in metastatic lesions.

The FRα vaccine include a pool of 5 peptides that are immunogenic epitopes and safely generate tissue-surveying CD4 T cell immune responses in patients tested in a recently completed phase I clinical trial.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Biological: Low dose FRα vaccine
  165ug per peptide ID injection
  Other Name: TPIV200
• Drug: Cyclophosphamide
  IV infusion over 1 hour
  Other Name: Cytoxan
• Biological: High dose FRα vaccine
  500ug per peptide ID injection
  Other Name: TPIV200

Study Arms

• Experimental: Low dose FRα vaccine
  FRα peptide vaccine with GM-CSF adjuvant - single ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
  Intervention: Biological: Low dose FRα vaccine
• Experimental: High dose FRα vaccine
  FRα peptide vaccine with GM-CSF adjuvant - triple ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
  Intervention: Biological: High dose FRα vaccine
• Experimental: Low dose FRα vaccine + cyclophosphamide
  Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FRα peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
  Interventions:

  • Biological: Low dose FRα vaccine
  • Drug: Cyclophosphamide
• Experimental: High dose FRα vaccine + cyclophosphamide
  Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FRα peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
  Interventions:

  • Drug: Cyclophosphamide
  • Biological: High dose FRα vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 30, 2015): 80
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 15, 2021
• Actual Primary Completion Date: July 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Female patient, age 18 years or older;
2. Completely resected unilateral or bilateral primary carcinoma of the breast
3. Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
4. Primary tumor was negative for ER, PR (cut-off for positivity is >10% positive tumor cells with nuclear staining) and negative for Her2-neu (0 or 1+ on immunohistochemistry and/or normal gene copy number by in-situ hybridization); Central review is not required.
5. Completed primary treatment (surgery and radio/chemotherapy in adjuvant and/or neo-adjuvant setting) <360 days prior to first vaccination.
6. Completed last cycle of chemotherapy or radiation > 60 days prior to first vaccination

7. Either clinical or pathological Stage I (T1c), II, or III according to AJCC 7th edition

   • Note that patients with (i) non-invasive breast cancer (DCIS) alone, (ii) incidental (microscopic) nodal cancer without a primary tumor (pN1mi), or (iii) metastatic disease are excluded.
   • Resected tumor: No evidence of gross tumor at the surgical resection margin noted in the final surgery report. No evidence of gross residual adenopathy
8. Karnofsky index >= 70%;
9. Life expectancy of at least 5 years, disregarding the diagnosis of cancer;

10. Adequate Blood, renal and hepatic function, as determined within 28 days from registration:

    • ANC ≥ 1,500 / mm3
    • Platelet ≥ 100,000 / uL
    • Hgb > 9 g/dL
    • Creatinine ≤ 1.5 x ULN or 24-hour urine < Grade 2
    • Urinalysis with < 2+ proteinuria
    • Serum albumin ≥ 3 g/dL
    • SGOT (AST) ≤ 3 x ULN
11. Anti-nuclear antibody (ANA) negative or low-positive institutional range, as determined within 28 days from registration. Intermediate values (usually defined by a titer of ≤1:80, or as indicated by institutional range) are acceptable if there are, in the opinion of the Investigator, no early signs of an autoimmune disease.
12. Primary tumor is available for shipment to central laboratory for analysis of FRα expression by IHC.
13. Patients must be, in the opinion of the Investigator, available and compliant for treatment and follow-up.

Exclusion Criteria:

1. Clinical evidence of distant metastases per practice guidelines for breast cancer;
2. Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion;
3. Known hypersensitivity reaction to the GM-CSF adjuvant; Any known contra-indication to GM-CSF or Cyclophosphamide treatment;
4. Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to registration and must implement adequate contraceptive measures during study treatment;
5. Active autoimmune disease requiring therapy within the past 2 years (Note: patients with vitiligo, Grave's disease or psoriasis not requiring systemic treatment within the past 2 years are not excluded);
6. Other uncontrolled illness or medical condition, such as active infection, symptomatic heart failure (New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease), unstable angina pectoris, myocardial infarction or stroke within last 6 months, psychiatric illness that may limit compliance with study requirement or interfere with the understanding and giving of informed consent;
7. Prior active secondary malignancy < 5 years prior to consent (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix) or currently receiving other specific treatment for this cancer (including monoclonal antibody or pathway inhibitor);
8. Completed treatment with systemic corticosteroid or immune-modulators < 30 days prior to registration;
9. Planned treatment with other experimental drugs or any other non-hormonal anti-cancer therapy;
10. Immunocompromised patients, including patients with known HIV infection;
11. Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin).

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02593227
• Other Study ID Numbers: FRV-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Marker Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Marker Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Richard Kenney, MD; Marker Therapeutics, Inc.

• PRS Account: Marker Therapeutics, Inc.
• Verification Date: July 2021