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

This first-in-human study of GEN-009 will be conducted in three 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 (Parts B and C 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 nivolumab at the
approved dose and schedule per the United States Package Insert (USPI). Part C will evaluate
the safety, immunogenicity, and objective response rate (ORR) of patients with the
above-noted tumor types who have received at least 1 line of standard systemic therapy that
included a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1)
inhibitor for advanced, recurrent, or metastatic disease.

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 (Parts B and C 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 full-dose nivolumab per disease as listed
below:

1. NSCLC: Patients with metastatic NSCLC with disease progression on or after
platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations
should have had disease progression on FDA-approved therapy for these aberrations
prior to receiving nivolumab

2. SCCHN: Patients with recurrent or metastatic SCCHN with disease progression on or
after a platinum-based therapy

3. Cutaneous Melanoma: Patients with unresectable or metastatic cutaneous melanoma
regardless of BRAF mutation status

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

1. Have had disease progression during or following platinum-containing
chemotherapy

2. Have disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy

5. Renal Cell Carcinoma: Patients with advanced renal cell carcinoma who have
received prior anti-angiogenic therapy.

- 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

Part C-specific Inclusion:

- Have received at least 1 line of standard systemic therapy for advanced, relapsed, or
metastatic disease

- Have received a PD-1 or PD-L1 inhibitor either as a single-agent or in combination,
and have had disease progression on the checkpoint inhibitor or disease that is
considered by the Investigator to be refractory to the checkpoint inhibitor

- In addition, Part C participants should have received the following chemotherapy:

1. NSCLC: A platinum-containing chemotherapy regimen

2. SCCHN: A platinum-containing chemotherapy regimen

3. Cutaneous Melanoma with a BRAF V600 mutation: An FDA-approved BRAF inhibitor

4. Urothelial carcinoma: A platinum-containing chemotherapy regimen.

5. Renal Cell Carcinoma: An anti-angiogenic therapy

- Have at least 1 lesion that is measureable by RECIST 1.1

- Agree to a tumor biopsy 50 days after first GEN-009 vaccination

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

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

Part B-specific Exclusion Criteria:

- Has received or requires additional anticancer treatment prior to first GEN-009
vaccination (however, these participants may be eligible for Part C)

Part C-specific Exclusion Criteria:

- Has received or requires additional anticancer treatment within 14 days of first
GEN-009 vaccination

- Has not recovered or stabilized from any clinically significant toxicity associated
with any prior procedure or anticancer therapy