Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine

Study Description

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Brief Summary:

In this study, Genocea is evaluating an investigational, personalized adjuvanted vaccine, GEN-009, that is being developed for the treatment of patients with solid tumors. A proprietary tool developed by Genocea, called ATLAS™ (Antigen Lead Acquisition System) will be used to identify neoantigens in each patient's tumor that are recognized by their CD4 and/or CD8 T cells. ATLAS-identified neoantigens will then be incorporated into a patient's personalized vaccine in the form of synthetic long peptides (SLPs).

Condition or disease	Intervention/treatment	Phase
Cutaneous Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Renal Cell Carcinoma	Biological: GEN-009 Adjuvanted Vaccine; Drug: Nivolumab	Phase 1; Phase 2

Detailed Description:

This first-in-human study of GEN-009 will be conducted in three parts in adult patients with cutaneous melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma, or renal cell carcinoma (Parts B and C only). In Part A, the safety and immunogenicity of single-agent GEN-009 will be evaluated in patients with the above-noted tumor types who have completed treatment with curative intent for their disease (eg, surgical resection, neoadjuvant and/or adjuvant chemotherapy, and/or radiation therapy) and have no evidence of disease (NED) at the time of initiating vaccination with GEN-009. In Part B, up to 15 patients in each disease cohort will be enrolled and evaluated for safety, immunogenicity, and preliminary antitumor activity of GEN-009. Patients in Part B will receive GEN-009 at the schedule selected in Part A, in combination with nivolumab at the approved dose and schedule per the United States Package Insert (USPI). Part C will evaluate the safety, immunogenicity, and objective response rate (ORR) of patients with the above-noted tumor types who have received at least 1 line of standard systemic therapy that included a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor for advanced, recurrent, or metastatic disease.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	124 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 1/2a Study to Evaluate the Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine in Adult Patients With Selected Solid Tumors
Actual Study Start Date :	August 29, 2018
Estimated Primary Completion Date :	December 2022
Estimated Study Completion Date :	December 2022

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Part A; Participants in Part A have no evidence of disease when they begin receiving GEN-009 Adjuvanted Vaccine, and have completed treatment with curative intent for their disease (eg, surgical resection, neoadjuvant and/or adjuvant chemotherapy, and/or radiation therapy). Part A will consist of approximately 9 participants.	Biological: GEN-009 Adjuvanted Vaccine; GEN-009 Adjuvanted Vaccine consists of GEN-009 Drug Product mixed with Hiltonol (poly-ICLC, adjuvant) and is administered by subcutaneous injection.
Experimental: Part B; Participants in Part B have advanced or metastatic solid tumors, and will receive GEN-009 Adjuvanted Vaccine in combination with nivolumab. Part B will consist of up to 75 participants.	Biological: GEN-009 Adjuvanted Vaccine; GEN-009 Adjuvanted Vaccine consists of GEN-009 Drug Product mixed with Hiltonol (poly-ICLC, adjuvant) and is administered by subcutaneous injection.; Drug: Nivolumab; Nivolumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.; Other Name: OPDIVO
Experimental: Part C; Participants in Part C have relapsed or refractory solid tumors, have received at least 1 line of standard systemic therapy that included a PD-1 or PD-L1 inhibitor for advanced, recurrent, or metastatic disease, and will receive GEN-009 Adjuvanted Vaccine as a monotherapy. Part C will consist of up to 40 participants.	Biological: GEN-009 Adjuvanted Vaccine; GEN-009 Adjuvanted Vaccine consists of GEN-009 Drug Product mixed with Hiltonol (poly-ICLC, adjuvant) and is administered by subcutaneous injection.

Outcome Measures

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Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 1.5 years after first GEN-009 vaccination ]
   Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
2. T-cell responses to GEN-009 adjuvanted vaccine [ Time Frame: 1.5 years after first GEN-009 vaccination ]
   Immunogenicity based on T-cell responses to GEN-009

Secondary Outcome Measures :

1. Antitumor activity of GEN-009 in Part B [ Time Frame: 48 weeks after first GEN-009 vaccination ]
   Evaluation conducted based on RECIST v1.1 (and immune-related RECIST [irRECIST], where appropriate)
2. Antitumor activity of GEN-009 in Part C [ Time Frame: 48 weeks after first GEN-009 vaccination ]
   Evaluation conducted based on RECIST v1.1

Other Outcome Measures:

1. Long-term clinical outcomes of Part A participants [ Time Frame: 1.5 years after first GEN-009 vaccination ]
   Disease recurrence
2. Additional cellular responses after vaccination with GEN-009 [ Time Frame: 1 year after first GEN-009 vaccination ]
   Cytokine secretion
3. Phenotype of circulating immune cells after vaccination with GEN-009 [ Time Frame: 1 year after first GEN-009 vaccination ]
   Measured by flow cytometry
4. Tumor-infiltrating T cells after vaccination with GEN-009 [ Time Frame: 1 year after first GEN-009 vaccination ]
   Will be examined in tumor biopsies

Eligibility Criteria

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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

General Inclusion Criteria:

• Diagnosis of 1 of the following tumor types:

  1. Melanoma (cutaneous).
  2. NSCLC.
  3. SCCHN (oral, oropharyngeal, hypopharyngeal, or laryngeal).
  4. Urothelial carcinoma.
  5. Renal cell carcinoma (Parts B and C only).
• Understand the study, be willing to comply with all study procedures and sign the informed consent
• Adequate tumor tissue available
• ECOG performance status of 0 or 1
• Negative pregnancy test (females of childbearing potential)
• Agree to use of contraception during the study until at least 90 days after final GEN-009 dose
• Adequate hematologic, liver, and kidney function

Part A-specific Inclusion:

• Have completed or will complete treatment for their disease with curative intent
• Have no evidence of disease

Part B-specific Inclusion:

• Receiving or will initiate treatment with full-dose nivolumab per disease as listed below:

  1. NSCLC: Patients with metastatic NSCLC with disease progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have had disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab
  2. SCCHN: Patients with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy
  3. Cutaneous Melanoma: Patients with unresectable or metastatic cutaneous melanoma regardless of BRAF mutation status

  4. Urothelial Carcinoma: Patients with locally advanced or metastatic urothelial carcinoma who:

     1. Have had disease progression during or following platinum-containing chemotherapy
     2. Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  5. Renal Cell Carcinoma: Patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.
• Disease assessment by CT or MRI
• Have at least 1 lesion that is measureable by RECIST 1.1
• Agree to a tumor biopsy 50 days after first GEN-009 vaccination
• Participants with hypothyroidism must be on thyroid replacement treatment

Part C-specific Inclusion:

• Have received at least 1 line of standard systemic therapy for advanced, relapsed, or metastatic disease
• Have received a PD-1 or PD-L1 inhibitor either as a single-agent or in combination, and have had disease progression on the checkpoint inhibitor or disease that is considered by the Investigator to be refractory to the checkpoint inhibitor

• In addition, Part C participants should have received the following chemotherapy:

  1. NSCLC: A platinum-containing chemotherapy regimen
  2. SCCHN: A platinum-containing chemotherapy regimen
  3. Cutaneous Melanoma with a BRAF V600 mutation: An FDA-approved BRAF inhibitor
  4. Urothelial carcinoma: A platinum-containing chemotherapy regimen.
  5. Renal Cell Carcinoma: An anti-angiogenic therapy
• Have at least 1 lesion that is measureable by RECIST 1.1
• Agree to a tumor biopsy 50 days after first GEN-009 vaccination

General Exclusion Criteria:

• Received a live vaccine ≤ 28 days, or a non-live vaccine ≤ 14 days, prior to the first dose of GEN-009
• Acute or chronic skin disorders that would interfere with injection
• Receiving immunosuppressive therapies or systemic corticosteroids. Note: Use of topical corticosteroids or inhaled corticosteroids is acceptable
• Allergy to the vaccine adjuvant Hiltonol (poly-ICLC)
• Active hepatitis B or hepatitis C infection
• HIV Positive
• History of clinically significant cardiac condition
• History of leptomeningeal carcinomatosis
• Had clinically active immune-mediated disease within 5 years
• Received a prior allogeneic stem cell transplant
• Has primary immune deficiency
• Received a prior solid organ transplant
• Has malignant disease, other than the tumor types being treated in this study
• Female patient who is pregnant, breastfeeding, or who plans to become pregnant from the signing of the informed consent until ≥ 90 days from last dose of GEN-009
• Any condition that in the judgment of the PI would make the patient inappropriate for enrollment in the study

Part A-specific Exclusion Criteria:

• Has received or requires more than 2 adjuvant or neoadjuvant regimens (other than surgical excisions) given with curative intent prior to first GEN-009 vaccination
• Has not recovered or stabilized from any clinically significant toxicity associated with any prior procedure or anticancer therapy

Part B-specific Exclusion Criteria:

• Has received or requires additional anticancer treatment prior to first GEN-009 vaccination (however, these participants may be eligible for Part C)

Part C-specific Exclusion Criteria:

• Has received or requires additional anticancer treatment within 14 days of first GEN-009 vaccination
• Has not recovered or stabilized from any clinically significant toxicity associated with any prior procedure or anticancer therapy

Contacts and Locations

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Contacts

Contact: Jennifer LaVin	617-876-8191	jennifer.lavin@genocea.com

Locations

United States, Arizona
Scottsdale Healthcare Hospitals DBA HonorHealth	Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer, RN 480-323-1339 clinicaltrials@honorhealth.com
Principal Investigator: Michael S. Gordon, MD
Sub-Investigator: Jasgit Sachdev, MD
Sub-Investigator: Erkut H. Borazanci, MD
Sub-Investigator: Sunil Sharma, MD
Sub-Investigator: Frank Y. Tsai, MD
United States, California
UC San Diego Moores Cancer Center	Recruiting
La Jolla, California, United States, 92093
Contact: Ashley Weaver 858-822-1962 aweaver@ucsd.edu
Principal Investigator: Sandip Patel, MD
John Wayne Cancer Institute - Providence Saint John's Health Center	Recruiting
Santa Monica, California, United States, 90404
Contact: Hunter Cole 310-449-5224 ColeH@jwci.org
Principal Investigator: Przemyslaw Twardowski, MD
Sub-Investigator: Steven J. O'Day, MD
United States, Colorado
University of Colorado, Anschutz Cancer Pavilion	Recruiting
Aurora, Colorado, United States, 80045
Contact: Kristen Califano 720-848-0592 kristen.califano@ucdenver.edu
Principal Investigator: Antonio Jimeno, MD, PhD
Sub-Investigator: Daniel W. Bowles, MD
Sub-Investigator: David R. Cambridge, MD, PhD
Sub-Investigator: Bradley R. Corr, MD
Sub-Investigator: Lindsey Davis, MD
Sub-Investigator: Jennifer R. Diamond, MD
Sub-Investigator: Lia Gore, MD
Sub-Investigator: Gentry GT King, MD
Sub-Investigator: Elaine T. Lam, MD
Sub-Investigator: Alexis D. Leal, MD
Sub-Investigator: Stephen Leong, MD
Sub-Investigator: Karl D. Lewis, MD
Sub-Investigator: Christopher H. Lieu, MD
Sub-Investigator: Jessica McDermott, MD
Sub-Investigator: Wells A. Messersmith, MD
Sub-Investigator: Jose M. Pacheco, MD
Sub-Investigator: Thomas W. Purcell, MD
Sub-Investigator: Victor M. Villalobos, MD, PhD
United States, New York
Columbia University Medical Center - Herbert Irving Pavilion	Recruiting
New York, New York, United States, 10032
Contact: Fawzia Ibrahim 212-342-3970 fi2158@cumc.columbia.edu
Principal Investigator: Mark Stein, MD
Sub-Investigator: Richard D. Carvajal, MD
Sub-Investigator: Gary K. Schwartz, MD
Sub-Investigator: Kevin Kalinsky, MD
Sub-Investigator: Charles Drake, MD, PhD
Sub-Investigator: Emerson Lim, MD
Sub-Investigator: June Hou, MD
Sub-Investigator: Matthew Ingham, MD
Sub-Investigator: Jessica Yang, MD
Sub-Investigator: Meghna Trivedi, MD
United States, Pennsylvania
Hospital of the University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Maryann Redlinger 215-662-7452 maryann.redlinger@uphs.upenn.edu
Principal Investigator: Roger Cohen, MD
Sub-Investigator: Ronac Mantami, MD
Sub-Investigator: Naomi Haas, MD
Sub-Investigator: Vivek Narayan, MD
Sub-Investigator: Charu Aggarwal, MD
Sub-Investigator: Joshua Bauml, MD
Sub-Investigator: Tara Mitchell, MD
United States, Tennessee
The Sarah Cannon Research Institute	Recruiting
Nashville, Tennessee, United States, 37203
Contact: Ask Sarah 615-339-4214 asksarah@sarahcannon.com
Principal Investigator: Melissa L. Johnson, MD
Sub-Investigator: Todd M. Bauer, MD
Sub-Investigator: Johanna C. Bendell, MD
Sub-Investigator: Howard A. Burris, III, MD
Sub-Investigator: Erika P. Hamilton, MD

Sponsors and Collaborators

Genocea Biosciences, Inc.

Investigators

Study Director:	Arthur P. DeCillis, MD

More Information

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Additional Information:

OPDIVO (nivolumab) United States Prescribing Information 

Responsible Party:	Genocea Biosciences, Inc.
ClinicalTrials.gov Identifier:	NCT03633110 History of Changes
Other Study ID Numbers:	GEN-009-101
First Posted:	August 16, 2018
Last Update Posted:	November 2, 2018
Last Verified:	November 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Genocea Biosciences, Inc.:

Vaccine; Personalized; Immunotherapy; Solid Tumor; Personal; Skin	Lung; Cancer; Bladder; Kidney; Melanoma; Carcinoma

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Non-Small-Cell Lung; Melanoma; Carcinoma, Squamous Cell; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms	Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms, Squamous Cell; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Kidney Diseases; Urologic Diseases