A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants 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 advancedmalignancy. Phase 2a Part 1 i. Arm A - locally recurrent or metastatic melanoma. Participantsmust 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 followingcriteria: 1) Disease progression to platinum-containing chemotherapy; 2) Failure toanti-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 ofprior anti-cancer therapies. iv. Arm D - locally recurrent or metastatic cSCC. Participants must have received nomore than 3 prior regimens for advanced or metastatic disease. Phase 2a Part 2 i.v. Arm E - Histologically or pathologically confirmed NSCLC thatis advanced or recurrent, without EGFR mutation or ALK rearrangement. Participantsmust have received at least one line but no more than three lines of prioranti-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 inthe 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 testingresults.

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

10. Last dose of previous anticancer therapy ≥ 21 days, radiotherapy > 21 days, orsurgical 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 ofAssessments.

13. Capable of understanding and complying with protocol requirements.

14. Signed and dated institutional review board/independent ethics committee-approvedinformed consent form before any protocol-directed screening procedures areperformed.

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 orthe 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 therapyor gene therapy.

6. Prior intolerance to anti-PD-(L)1 monoclonal antibody or history of immunotherapyrelated 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 studytreatment (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 positiveserological test at Screening within 14 days of dosing with T3011.

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

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/pneumonitisrequiring treatment with systemic steroids.

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

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

21. 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.