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

• ClinicalTrials.gov Identifier: NCT03633110
• Recruitment Status: Active, not recruiting
• First Posted: August 16, 2018
• Last Update Posted: May 6, 2020
• Sponsor: Genocea Biosciences, Inc.
• Information provided by (Responsible Party): Genocea Biosciences, Inc.

Study Description

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; Drug: Pembrolizumab	Phase 1; Phase 2

Detailed Description:

This first-in-human study of GEN-009 will be conducted in two 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 (Part B 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 a PD-1 inhibitor therapy (nivolumab or pembrolizumab) at the approved dose and schedule per the United States Package Insert (USPI). In addition, up to 15 patients who enroll in one of the Part B disease-specific cohorts but whose disease progresses during the screening period therapy may be enrolled into a separate relapsed/refractory disease cohort.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 99 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

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 PD-1 inhibitor therapy (nivolumab or pembrolizumab). Part B will consist of up to 90 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; Drug: Pembrolizumab; Pembrolizumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.; Other Name: KEYTRUDA

Outcome Measures

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)

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

• 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 (Part B 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 nivolumab or pembrolizumab per disease as listed below:

  1. NSCLC: Patients with metastatic non-squamous NSCLC beginning first-line pembrolizumab in combination with pemetrexed and platinum chemotherapy, or metastatic squamous NSCLC beginning first-line pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel
  2. SCCHN: Patients beginning pembrolizumab with recurrent or metastatic SCCHN with disease progression on or after a platinum-based therapy, or beginning first-line pembrolizumab for recurrent or metastatic SCCHN if tumors express PD-L1 with a Combined Positive Score (CPS) ≥ 1.
  3. Cutaneous Melanoma: Patients with unresectable or metastatic cutaneous melanoma beginning nivolumab monotherapy or nivolumab in combination with ipilimumab.

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

     1. Are not eligible for cisplatin-containing chemotherapy, and tumor is PD-L1 positive with CPS ≥ 10, or are not eligible for any platinum-containing chemotherapy, OR
     2. Have had disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

  5. Renal Cell Carcinoma:

     1. Patients with advanced RCC who have received prior anti-angiogenic therapy, and are beginning nivolumab monotherapy, OR
     2. Untreated patients with intermediate or poor risk RCC based on the IMDC score who are beginning nivolumab in combination with ipilimumab.
• 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

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
• Patient has received cytotoxic chemotherapy within 4 weeks of the first leukapheresis

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

Contacts and Locations

Locations

United States, California

UC San Diego Moores Cancer Center

La Jolla, California, United States, 92093

John Wayne Cancer Institute - Providence Saint John's Health Center

Santa Monica, California, United States, 90404

United States, Colorado

University of Colorado, Anschutz Cancer Pavilion

Aurora, Colorado, United States, 80045

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New York

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States, 10032

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

The Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Wisconsin

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Genocea Biosciences, Inc.

Investigators

• Study Director: Arthur P. DeCillis, MD

More Information

Additional Information:

OPDIVO (nivolumab) United States Prescribing Information 

• Responsible Party: Genocea Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT03633110
• Other Study ID Numbers: GEN-009-101
• First Posted: August 16, 2018
• Last Update Posted: May 6, 2020
• Last Verified: May 2020

• 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; Melanoma; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Carcinoma, Squamous Cell; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Kidney Diseases; Urologic Diseases; Head and Neck Neoplasms; Pembrolizumab; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents