MarkV-01: This study is evaluating how safe, tolerable and effective a new targeted therapy is when given alone, or in combination with immunotherapy, in people with advanced or metastatic solid cancersA Phase 1a/1b, First-in-Human, Open Label Study to Assess the Safety, Tolerability, and Pharmacokinetics of PMC-309 (Anti-VISTA), as Monotherapy and Combined With Pembrolizumab, in Patients With Advanced or Metastatic Solid Tumors

Exclusion

A participant who meets ANY of the following exclusion criteria must be excluded from the study:

1. Has received treatment with a VISTA targeting agent.
2. Has a history of positive testing for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus) or other clinically active liver disease, or positive testing at Screening for HBsAg or anti- hepatitis C virus.
3. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
4. Has a medical condition which, in the opinion of the PI (or designee), places the participant at an unacceptably high risk for toxicity.
5. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
6. Is currently participating in or has participated in a study of an investigational agent or have received anticancer immunotherapy within 4 weeks prior to the first dose of IP.
7. Has an active autoimmune disease with a history of flares requiring immunosuppressant medications within the past 6 months or that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
8. History of known or suspected seizure disorder.
9. Has oxygen-dependent chronic disease.
10. Serious Grade 4 venous thromboembolic event including pulmonary embolism.
11. Participant is receiving therapeutic anticoagulants.
12. Has had an allogeneic tissue/solid organ transplant.
13. Major surgery (eg, requiring general anesthesia) within 4 weeks before the planned first dose of the IP, or not fully recovered from prior surgery, or has surgery planned during the time the participant is expected to participate in the study or within 4 weeks after the last dose of IP.

14. Fertility exclusions:

    1. Participant is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 120 days after the last dose of IP; WOCBP must have a negative pregnancy status confirmed by urine pregnancy test at Screening and within 72 hours of first dose of the IP. (If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.)
    2. Participant is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of the IP.
    3. Male participants must also refrain from sperm donation during the treatment period and for 5 terminal half-lives (of PMC-309) plus an additional 90 days (a spermatogenesis cycle).

    Note: The half-life of PMC-309 is 47 hours.

15. Vaccinated with a live vaccine within 30 days (with the exception of the annual inactivated influenza vaccine) prior to the first dose of the IP.
16. Received COVID-19 vaccine within 7 days of the first IP administration.
17. Any medical condition for which, in the opinion of the PI or designee, participation would not be in the best interest of the participant (eg, compromise the well-being of the participant) or that could prevent, limit, or confound the protocol specified assessments.
18. Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension; poorly controlled diabetes; ongoing active infection requiring antibiotics or acute infectious illness (including suspected viral infection); symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia considered to increase risk for the participant by the PI (or designee); or active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder, treated depression with ongoing antidepressant medication etc.) that would limit compliance with study requirements.
19. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of IP.
20. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression for at least 4 weeks by repeat imaging [note that the repeat imaging should be performed during Screening], clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of IP).
21. Prior allogeneic organ or bone marrow transplant.

22. Participant has had prior therapy meeting the following:

    1. Prior T-cell receptor-modified or chimeric antigen receptor T-cell (CART) therapy.
    2. Other anticancer therapy, including chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 4 weeks prior to the first dose of IP.
    3. Has received prior radiotherapy (excluding limited palliative radiation) within 2 weeks of start of IP or has a history of radiation pneumonitis.
    4. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (less than and equal to 2 weeks of radiotherapy) to non-CNS disease.
    5. Except for hearing loss, alopecia and pigmentation, all toxicity caused by previous anti-tumor therapy has recovered to Grade 1 or less.
23. Participant received prior therapy with an anti-PD-1 or anti-PD-L1 mAb or with an agent targeting stimulatory or co-inhibitory T-cell receptors and was discontinued from that treatment due to a Grade 3 or higher immune related AE.
24. Participant has an active autoimmune disease that required systemic treatment in the past.
25. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
26. Class III or IV heart failure by New York Heart Association (NYHA) classification.
27. History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of IP administration.
28. History of serious gastrointestinal hemorrhage within 6 months prior to start of IP administration.
29. History of hypertensive crisis or hypertensive encephalopathy.
30. History of posterior reversible encephalopathy syndrome.
31. Social situation that would limit compliance with study requirements.
32. A diagnosis of immunodeficiency or is receiving chronic systemic corticosteroids at a dose that exceeds 10 mg daily of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior the first dose of the IP. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.