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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Sub-Investigator: Gregory Daniels, MD, PhD
Sub-Investigator: Mina Nikanjam, MD, PhD
Sub-Investigator: Lyudmila Bazhenova, MD
Sub-Investigator: Kathryn Gold, MD
Sub-Investigator: Ezra Cohen, MD
Sub-Investigator: Assuntina Sacco, MD
Sub-Investigator: Rana McKay, MD
Sub-Investigator: James Randall, MD
Sub-Investigator: Frederick Millard, MD
Sub-Investigator: Shumei Kato, 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, Massachusetts
Dana-Farber Cancer Institute	Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Kristina Kelley 617-632-4976 kristinam_kelley@dfci.harvard.edu
Principal Investigator: Mark Awad, MD, PhD
Sub-Investigator: Frank S. Hodi, MD
Sub-Investigator: Osama Rahma, MD
Sub-Investigator: Patrick Ot, PhD
United States, Michigan
Karmanos Cancer Institute	Recruiting
Detroit, Michigan, United States, 48201
Contact: Amanda Newman 313-576-8411 newmana@karmanos.org
Principal Investigator: Ulka Vaishampayan, MD
Sub-Investigator: Hirva Mamdani, MD
Sub-Investigator: Amy Weise, MD
Sub-Investigator: Misako Nagasaka, MD
Sub-Investigator: Ira Winer, MD, PhD
Sub-Investigator: Anteneh Tesfaye, MD
Sub-Investigator: Anthony Shields, MD, PhD
Sub-Investigator: Ammar Sukari, MD
Sub-Investigator: Mary Josephine P Pilat, PhD
Sub-Investigator: Joseph Uberti, MD, PhD
Sub-Investigator: Abhinav Deol, MD
Sub-Investigator: Voravit Ratanatharathorn, MD
Sub-Investigator: Lois Ayash, MD
Sub-Investigator: Asif Alavi, MD
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
United States, Texas
The University of Texas MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Debora Clay 713-745-0294 daclay@mdanderson.org
Principal Investigator: Maura Gillison, MD, PhD
Sub-Investigator: George Blumenschein Jr., MD
Sub-Investigator: Lauren Byers, MD
Sub-Investigator: Frank Fossella, MD
Sub-Investigator: Don Gibbons, MD, PhD
Sub-Investigator: Bonnie Glisson, MD
Sub-Investigator: John Heymach Jr., MD, PhD
Sub-Investigator: Jonathan Kurie, MD
Sub-Investigator: George Simon, MD
Sub-Investigator: Vassiliki Papadimitrakopoulou, MD
Sub-Investigator: Faye Johnson, MD
Sub-Investigator: Frank E Mott, MD
Sub-Investigator: Charles Lu, MD
Sub-Investigator: Jianjun Zhang, MD, PhD
Sub-Investigator: Ferdinandos Skoulidis, MD, PhD
Sub-Investigator: Vincent Lam, MD
Sub-Investigator: Mehmet Altan, MD
Sub-Investigator: Anne S Tsao, MD
Sub-Investigator: Renata Ferrarotto, MD
Sub-Investigator: Xiuning Le, MD
Sub-Investigator: Diana Bell, MD
Sub-Investigator: Jeffrey Myers, MD
Sub-Investigator: Neil Gross, MD
Sub-Investigator: Yasir Elamin, MD
Sub-Investigator: Sanjay Gupta, MD
Sub-Investigator: Michelle Williams, MD

Sponsors and Collaborators

Genocea Biosciences, Inc.

Investigators

Study Director:	Arthur P. DeCillis, MD

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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:	January 3, 2019
Last Verified:	January 2019

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