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

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:
5. 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
6. Have had disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
7. Renal Cell Carcinoma:
8. Patients with advanced RCC who have received prior anti-angiogenic therapy, and are beginning nivolumab monotherapy, OR
9. 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