Clinical Trials /

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

NCT03633110

Description:

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).

Related Conditions:
  • Cutaneous Melanoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Renal Cell Carcinoma
  • Squamous Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, Tolerability, Immunogenicity, and Antitumor Activity of GEN-009 Adjuvanted Vaccine
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GEN-009-101
  • NCT ID: NCT03633110

Conditions

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

Interventions

DrugSynonymsArms
GEN-009 Adjuvanted VaccinePart A
NivolumabOPDIVOPart B
PembrolizumabKEYTRUDAPart B

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalParticipants 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.
  • GEN-009 Adjuvanted Vaccine
Part BExperimentalParticipants 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.
  • GEN-009 Adjuvanted Vaccine
  • Nivolumab
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:1.5 years after first GEN-009 vaccination
Safety Issue:
Description:Adverse events will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genocea Biosciences, Inc.

Trial Keywords

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

Last Updated

October 4, 2019