Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers

NCT02725489 | Completed Phase 2 FDA Drug

• 3 other identifiers: 16-06CL-PTL 124ESR-15-11306
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the researchers want to learn more about Vigil and durvalumab in advanced women's cancers: 1) how much of Vigil in combination with durvalumab (MEDI4736) can be given with an acceptable level of side effects, 2) the effects of Vigil and durvalumab in combination (good and bad), 3) if Vigil will cause changes in cancer cells that may help durvalumab attack the cancer, and 4) whether or not Vigil and durvalumab will slow your cancer or stop your cancer from getting worse. Combining Vigil with durvalumab will allow the former to induce (or increase) the infiltration of activated T cells into tumors, and in addition, to enhance PD-L1 (programmed cell death ligand 1) expression. Consequently, the response rate of historically low or un-responsive cancer will be increased with the combination of Vigil and anti PD-L1.

Conditions

Breast Cancer; Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Uterine Cancer; Cervical Cancer; Endometrial Cancer

Keywords

Vigil; durvalumab; MEDI4736; PD-L1; anti PD-L1; immunotherapy; PD-L1 inhibitor; breast cancer; ovarian cancer; fallopian tube cancer; primary peritoneal cancer; uterine cancer; cervical cancer; endometrial cancer

Outcome Measures

Primary Outcomes (1)

• Number of treatment-emergent AEs of Vigil + Durvalumab

  The safety evaluation will include collection of AEs, SAEs and changes from baseline in laboratory evaluations, vital signs, ECGs and physical exams. AEs will be graded according to the NCI CTCAE v4.03.

  Up to 90 days after last dose of study treatment

Secondary Outcomes (3)

• Overall response rate (ORR)

  Up to 12 months after start of study treatment

• Disease status

  Up to 12 months after start of study treatment

• IFNγ-ELISPOT conversion rate (negative to positive) during on-study treatment

  12 weeks after start of study treatment

Study Arms (3)

Part 1 Cohort 1: 1x10^6 cells Vigil

EXPERIMENTAL

The first part will be a safety run-in comprised of 2 cohorts that will use a 3 + 3 design to determine the Vigil dose in Part 2. Cohort 1 will receive a low dose of Vigil (1x10\^6 cells/intradermal (ID) injection) in combination with durvalumab (1500 mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

Biological: Vigil; Drug: Durvalumab

Part 1 Cohort 2: 1x10^7 cells Vigil

EXPERIMENTAL

Cohort 2 will receive Vigil at 1x10\^7 cells/ID injection and durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

Biological: Vigil; Drug: Durvalumab

Part 1 Cohort -1: 1x10^5 cells Vigil

EXPERIMENTAL

If needed, Cohort -1 will be used which will receive Vigil at 1x10\^5 cells/ID injection and Durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

Biological: Vigil; Drug: Durvalumab

Interventions

Vigil BIOLOGICAL

Vigil is made up of irradiated autologous tumor cells which have been electroporated ex vivo with the Vigil plasmid designed to suppress expression of both the TGFβ1 and TGFβ2 proteins while simultaneously expressing rhGMCSF protein.

Also known as: bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy, FANG

Part 1 Cohort -1: 1x10^5 cells Vigil; Part 1 Cohort 1: 1x10^6 cells Vigil; Part 1 Cohort 2: 1x10^7 cells Vigil

Durvalumab DRUG

A human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against programmed cell death ligand 1 (PD-L1)

Also known as: MEDI4736

Part 1 Cohort -1: 1x10^5 cells Vigil; Part 1 Cohort 1: 1x10^6 cells Vigil; Part 1 Cohort 2: 1x10^7 cells Vigil

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document for tissue harvest
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Histologically or cytologically confirmed diagnosis of women's cancer, inclusive, but not limited to breast, ovarian, fallopian tube, primary peritoneal, uterine, cervical, endometrial, that is locally advanced or metastatic for which the projected response rate to durvalumab is 15% or less.
• Female patients age ≥ 18 years
• No prior Vigil immunotherapy
• Treatment-naïve or refractory (no response to checkpoints) / resistant (initial response but relapse) to PD-1 or PD-L1 inhibitor therapy
• ECOG Performance Status ≤ 1
• Estimated survival ≥ 6 months
• Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of \~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.
• One lesion not previously irradiated nor intended for vaccine manufacture, which can be biopsied with minimal invasion and measurable at baseline as per RECIST 1.1 guidelines (performed prior to biopsy) or 2 lesions not previously irradiated nor intended for vaccine manufacture, one of which can be biopsied with minimal invasion and the other of which is measurable at baseline as per RECIST 1.1 guidelines. If the only such target lesion has previously been irradiated it must have shown unequivocal evidence of disease progression following completion of radiation therapy. Alternative methods of disease assessment, e.g. measurement of tumor markers or ascites/pleural fluid, may be considered by the Sponsor on a case-by-case basis.
• Provision of tumor tissue sample (archived or fresh) to allow for PD-L1 expression analysis
• Successful manufacturing of at least 4 vials of Vigil.
• Ability to understand and the willingness to sign a written informed consent document
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Estimated survival of ≥ 6 months

You may not qualify if:

• Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study.
• Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily for \< 30 days duration.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent.
• Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 5 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
• History of brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 4 months.
• Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids (unless within the protocol allowed doses).
• Known history of allergies or sensitivities to gentamicin, Durvalumab, or any excipient.
• History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Known HIV or acute or chronic Hepatitis B or C infection.
• History of pneumonitis or interstitial lung disease.
• History of organ transplant that requires therapeutic immunosuppression
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of Peptic Ulcer Disease or gastritis
• History of primary immunodeficiency
• History of leptomeningeal carcinomatosis

Sponsors & Collaborators

• Mary Crowley Medical Research Center: lead
• Gradalis, Inc.: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Uterine Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms

Interventions

FANG vaccine; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Diseases; Uterine Cervical Diseases

Study Officials

• Minal Barve, MD

  Mary Crowley Cancer Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2016
• First Posted: April 1, 2016
• Study Start: June 3, 2016
• Primary Completion: December 30, 2019
• Study Completion: December 2, 2020
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)