A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors

Inclusion Criteria:

• At least 18 years of age.

• Participants must have histologically confirmed locally advanced, recurrent ormetastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy).

• Participants must have progressed on or be intolerant of available standard of caretreatment options or have disease for which there is no standard of care treatmentavailable, with the exception of participants enrolling to the neoadjuvant cohorts.

• At least 2 lesions of measurable disease, unless specified otherwise in theselection criteria.

• Willingness to undergo biopsies.

• Demonstrated adequate organ function within 28 days of Cycle 1 Day 1 (C1D1).

• Life expectancy >12 weeks as determined by the Investigator.

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

• Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or antiCTLA 4antibody must have at least 4 weeks from the last dose of antibody and evidence ofdisease progression per investigator assessment before enrollment.

• Participants who have previously received an immune checkpoint inhibitor prior toenrollment must have any immune related toxicities resolved to ≤Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible.

• Female and male participants of childbearing potential who are sexually active mustagree to use highly effective methods of contraception.

Exclusion Criteria:

• Participants who have been previously treated with a TLR agonist (excluding topicalagents for unrelated disease) are not eligible.

• Other active malignancies within the last 2 years are excluded.

• Active autoimmune diseases, regardless of need for immunosuppressive treatment atthe time of screening, with the exception of patients well controlled on physiologicendocrine replacement.

• Systemic immunosuppressive treatment with the exception for patients oncorticosteroid taper (for example, for chronic obstructive pulmonary diseaseexacerbation). Participants cannot start dosing on study until steroid dose is at orlower than 10 mg per day prednisone or equivalent.

• Women who are breastfeeding or have a positive serum pregnancy test during screeningor within 72 hours prior to C1D1 are not eligible.

• Vaccination with live, attenuated vaccines within 4 weeks of enrollment.

• Symptomatic central nervous system metastases.

• Known bleeding disorder that is deemed to place the patient at unacceptable risk forbleeding complications from intratumoral injections or biopsies.

• Known hypersensitivity to any component of TransCon TLR7/8 Agonist or pembrolizumab.

• Any uncontrolled bacterial, fungal, viral, or other infection.

• Treatment with any other anti-cancer systemic treatment (approved orinvestigational) or radiation therapy within 4 weeks of first dosing on study is notallowed.

• Significant cardiac disease

• A marked baseline prolongation of QT/QTc (corrected QT) interval (e.g., repeateddemonstration of a QTc interval >480 ms (National Cancer Institute NCI) CommonTerminology Criteria for Adverse Events [CTCAE] grade 1) using Fredericia's QTcorrection formula.

• A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heartfailure, clinically significant hypokalemia, family history of Long QT Syndrome).

• The use of concomitant medications that prolong the QT/QTc interval within 14 daysof enrollment.

• Positive for HIV or with active hepatitis B or C infection.