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

NCT ID: NCT03633110

Last Updated: 2022-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-29
• Study Completion Date: 2022-02-28

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).

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.

Conditions

Cutaneous Melanoma; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of the Head and Neck; Urothelial Carcinoma; Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GEN-009 Adjuvanted Vaccine

Intervention Type: BIOLOGICAL

GEN-009 Adjuvanted Vaccine consists of GEN-009 Drug Product mixed with Hiltonol (poly-ICLC, adjuvant) and is administered by subcutaneous injection.

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.

Group Type: EXPERIMENTAL

GEN-009 Adjuvanted Vaccine

Intervention Type: BIOLOGICAL

GEN-009 Adjuvanted Vaccine consists of GEN-009 Drug Product mixed with Hiltonol (poly-ICLC, adjuvant) and is administered by subcutaneous injection.

Nivolumab

Intervention Type: DRUG

Nivolumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.

Interventions

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.

Intervention Type: BIOLOGICAL

Nivolumab

Nivolumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab is a PD-1 checkpoint inhibitor approved by the FDA to treat the tumor types in this study.

Intervention Type: DRUG

Other Intervention Names

OPDIVO; KEYTRUDA

Eligibility Criteria

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

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genocea Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arthur P. DeCillis, MD

Role: STUDY_DIRECTOR

Locations

UC San Diego Moores Cancer Center

La Jolla, California, United States

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

Santa Monica, California, United States

University of Colorado, Anschutz Cancer Pavilion

Aurora, Colorado, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

The Sarah Cannon Research Institute

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States

Countries

United States

Related Links

https://rm2.scinet.fda.gov/druglabel/rs/spl/by-id/242058/242058.html

OPDIVO (nivolumab) United States Prescribing Information

Other Identifiers

GEN-009-101

Identifier Type: -

Identifier Source: org_study_id