A Phase I/2a, Open-Label, Dose Escalation and Expansion study of the Safety and Tolerability of T3011 Administered via Intertumoral Injection as a Single agent in Combination with Intravenous Pembrolizumab in Patients with Advanced or Metastatic Solid Tumors

This is a Phase 1/2a, open-label, study to evaluate the safety and preliminary efficacy of
intratumoral T3011 given alone and in combination with intravenous pembrolizumab in partients
with advanced or metastatic solid tumors.

Key Inclusion Criteria:

1. Age 18 years or older.

2. Disease progression after standard of care (SOC) therapy or in the opinion of

3. The Investigator unlikely to benefit from SOC therapy. Inclusion Diagnosis Phase 1 -
Histologically or pathologically confirmed locally recurrent or metastatic advanced
malignancy.

Phase 2a Part 1 i. Arm A - locally recurrent or metastatic melanoma. Participants must
have received no more than 3 prior regimens for advanced or metastatic disease.

ii. Arm B - locally recurrent or metastatic HNSCC. It must also meet the following
criteria: 1) Disease progression to platinum-containing chemotherapy; 2) Failure to
anti-PD-1/PDL1 blockade after receiving at least 2 doses alone or in combination.

iii. Arm C - Sarcoma. Participants must have received no more than three lines of
prior anti-cancer therapies.

iv. Arm D - locally recurrent or metastatic cSCC. Participants must have received no
more than 3 prior regimens for advanced or metastatic disease.

Phase 2a Part 2 i.v. Arm E - Histologically or pathologically confirmed NSCLC that is
advanced or recurrent, without EGFR mutation or ALK rearrangement. Participants must
have received at least one line but no more than three lines of prior anti-cancer
therapies.

4. Measurable disease per RECIST version 1.1.

5. Must have at least 1 tumor lesion that is accessible for IT injection of T3011 in the
opinion of the investigator.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

7. Life expectancy > 12 weeks.

8. Demonstrate adequate organ function as defined by acceptable laboratory testing
results.

9. Women of child-bearing potential (WCBP) and men must agree to use adequate
contraception prior to study entry, while on study treatment, and for six months after
receiving last dose of T3011. WCBP must have a negative serum pregnancy test prior to
W1D1.

10. Last dose of previous anticancer therapy ≥ 21 days, radiotherapy > 21 days, or
surgical intervention > 21 days prior to the first dose of T3011.

11. Recovered from all prior anticancer therapy toxicities.

12. Willingness to provide fresh tumor biopsy specimens as specified in the Schedule of
Assessments.

13. Capable of understanding and complying with protocol requirements.

14. Signed and dated institutional review board/independent ethics committee-approved
informed consent form before any protocol-directed screening procedures are performed.

Key Exclusion Criteria:

1. Have only uninjectable tumors..

2. Patients with injectable tumors impinging upon major airways or blood vessels.

3. HNSCC only: Prior re-irradiation field containing carotid artery.

4. Greater than 3 distant metastatic lymph node regions and/or metastatic lesions or the
largest distant metastases with a diameter of more than 3 cm (non-sarcoma)/5 cm
(sarcoma) unless the lesion is to be injected.

5. Prior treatment with another OV (including T-VEC), tumor vaccines, cellular therapy or
gene therapy.

6. Prior intolerance to anti-PD-(L)1 monoclonal antibody or history of immunotherapy
related non-infectious pneumonitis/interstitial lung disease.

7. Prior treatment with anti-PD-(L)1 monoclonal antibody in combination with IL-12.

8. Requires continued concurrent therapy with any drug active against HSV.

9. Live vaccines, attenuated vaccines within 4 weeks prior to initiation of study
treatment (participants vaccinated with inactivated vaccines can be enrolled.

10. Primary or acquired immunodeficient states.

11. Pregnant or lactating.

12. Prior organ transplantation.

13. Active hepatitis B virus, hepatitis C virus, and HIV infection or a positive
serological test at Screening within 14 days of dosing with T3011.

14. Active autoimmune disease or medical conditions requiring chronic steroid or
immunosuppressive therapy within 4 weeks prior to first administration of study
treatment.

15. History of or current central nervous system metastases.

16. History of seizure disorders within 6 months of Screening.

17. Active oral or skin herpes lesion at Screening.

18. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis
requiring treatment with systemic steroids.

19. Congestive heart failure, active coronary artery disease, unevaluated new onset angina
within 3 months or unstable angina, or clinically significant cardiac arrhythmias.

20. History of allergic reactions attributed to compounds of similar biological
composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody.

18. Active infection with SARS-CoV-2 virus. 21. Participants with moderate to large amount
of pleural effusion, ascites or pericardial effusion who need drug or medical intervention.

22. Other systemic conditions or organ abnormalities that, in the opinion of the
investigator, may interfere with the conduct and/or interpretation of the current study.