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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

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

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Arthur P. DeCillis, MD

Role: Study Director

Affiliation: N/A

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION