This is a Phase 2 study designed to determine the preliminary anti-tumor activity and confirm
the safety of VV1 in combination with cemiplimab. The study will concurrently enroll patients
with four distinct advanced malignancies in 5 separate tumor cohorts. The four cancers type
are NSCLC and melanoma that are progressing on CPI treatment, CPI-naïve HCC, and
treatment-naïve Endometrial.
Patients with melanoma will be enrolled into two parallel cohorts; in one cohort (Intravenous
melanoma cohort) patients will receive IV VV1 and patients in the other cohort (Intratumoral
melanoma cohort) will receive both IV VV1 and Intratumoral VV1; both cohorts will receive IV
cemiplimab in combination therapy with VV1 treatment. Patients with NSCLC, HCC or endometrial
cancer will receive IV VV1 and IV cemiplimab combination therapy.
Key Inclusion Criteria
1. Age ≥18 years on day of signing informed consent.
2. Specific by tumor cohorts:
- For the HCC cohort, confirmed diagnosis of inoperable HCC by histology or
clinical/radiological criteria. Progressed on, or intolerant to, one prior line
of systemic therapy. Child Pugh Score A or B7.
- For the NSCLC cohort, histologically confirmed diagnosis of advanced and/or
metastatic NSCLC in which radiological progression has been demonstrated during
therapy with a PD(L)1 immune CPI and for which no existing options are felt to
provide clinical benefit (only one line of PD-(L)1 therapy is permitted).
Progression during or following 1 or more prior regimen(s) and no more than 3
prior therapeutic regimens for metastatic disease.
- For the melanoma cohorts, histologically confirmed diagnosis of advanced and/or
metastatic melanoma in which radiological progression has been demonstrated
during therapy with a PD(L)1 immune CPI and for which no existing options are
considered to provide clinical benefit (only one line of PD(L)1 therapy is
permitted). Progression on ipilimumab is not required. Note: For IT melanoma
cohort:
- i. At least one tumor lesion amenable to repeated IT injection via palpation
or ultrasound. Injection of deep visceral lesions is not permitted.
- ii. Agrees to provide a newly obtained biopsy of injected and witness
lesions prior to start of study treatment, and to repeat biopsies twice
during study treatment, and to providing the acquired tissue for biomarker
analysis. Tissue obtained for the biopsy must not be previously irradiated,
but a new or progressing lesion in the radiation field is acceptable.
- For the endometrial cancer cohort, histologically confirmed diagnosis of advanced
and/or metastatic endometrial adenocarcinoma. Eligible patients will have
progressed on, or be intolerant to, one line of prior systemic therapy and are
not candidates for curative surgery or radiation.
3. For patients treated with prior anti-PD-(L)1 therapy:
- Last dose of anti-PD-(L)1 must be within 12 weeks of initiating study treatment.
- Patient must have received at least 4 doses on q2w, 3 doses on q3w or 2 doses on
q4w schedule of the previous anti-PD-(L)1 therapy.
- Progression on prior anti-PD-(L)1 therapy must be defined by:
- Documented radiographic progression on a single radiographic scan, if treatment
with anti-PD-(L)1 was ≥ 16 weeks.
- Documented radiographic progression on two consecutive radiographic scans at
least 4 weeks apart, if treatment with anti-PD-(L)1 therapy was between 8 - 16
weeks; if radiographic progression is accompanied with clinical progression, then
a single scan assessment may be used.
- If progression was only in lymph nodes, biopsy to provide histological
confirmation of progression in the lymph node is required.
4. Measurable disease based on RECIST 1.1.
Key Exclusion criteria: Patients meeting any of the following exclusion criteria at
screening/Day -1 of first dosing will not be enrolled in the study
1. Availability of and patient acceptance of an alternative curative therapeutic option.
2. Recent or ongoing serious infection, including any active Grade 3 or higher per the
National Institute of Cancer Common Terminology Criteria for Adverse Events Version
5.0 (NCI CTCAE, v5.0) viral, bacterial, or fungal infection within 2 weeks of
registration.
3. Known seropositivity for and with active infection by the human immunodeficiency virus
(HIV).
• Patients who are seropositive for HIV but are receiving antiviral therapy and show
non-detectable viral load and a normal CD4 T cell count for at least 6 months are
eligible.
4. Seropositive for and with evidence of active viral infection with hepatitis B virus
(HBV). Patients who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA
negative are eligible.
- Patients who had HBV but have received an antiviral treatment and show
non-detectable viral DNA for 6 months are eligible.
- Patients who are seropositive because of HBV vaccine are eligible.
5. Seropositive for and with active viral infection with hepatitis C virus (HCV).
• Patients who had HCV but have received an antiviral treatment and show no detectable
HCV viral DNA for 6 months are eligible.
6. Known history of active or latent TB (bacillus tuberculosis).
7. Any concomitant serious health condition, which, in the opinion of the investigator,
would place the patient at undue risk from the study, including uncontrolled
hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic
obstructive pulmonary disease requiring hospitalization within 3 months) or
neurological disorder (e.g., seizure disorder active within 3 months).
8. Prior therapy within the following timeframe before the planned start of study
treatment as follows:
- Small molecule inhibitors, and/or other investigational agent: ≤ 2 weeks or 5
half-lives, whichever is shorter.
- Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other
similar experimental therapies: ≤ 3 weeks or 5 half-lives, whichever is shorter.
- Antibody drug conjugates and radioimmunoconjugates or other similar experimental
therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
9. New York Heart Association (NYHA) classification III or IV, known symptomatic coronary
artery disease, or symptoms of coronary artery disease on systems review, or known
cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia).
10. Any known or suspected active organ-threatening autoimmune disease, such as
inflammatory bowel disease, autoimmune hepatitis, lupus, or pneumonitis, with the
exception of hypothyroidism and type 1 diabetes that are controlled with treatment.
11. Immunodeficiency or immunosuppression
12. History of Grade 3 or 4 immune-mediated adverse reaction to immune CPIs.
13. Toxicities from previous therapies that have not resolved to a Grade 1 or less.
14. History of non-infectious pneumonitis that required steroids, or current pneumonitis.
