TCTLR: This Phase I/II trial is trying to evaluate how safe and tolerable a new cancer drug (TransCon TLR7/8 Agonist) alone, and in combination with immunotherapy (Pembrolizumab) in people with advanced or metastatic solid cancersPhase 1/2, Open-label, Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumor Malignancies

Exclusion

• Participants who have been previously treated with a TLR agonist (excluding topical agents 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 at the time of screening, with the exception of patients well controlled on physiologic endocrine replacement.
• Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation). Participants cannot start dosing on study until steroid dose is at or lower than 10 mg per day prednisone or equivalent.
• Women who are breastfeeding or have a positive serum pregnancy test during screening or 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 for bleeding 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 or investigational) or radiation therapy within 4 weeks of first dosing on study is not allowed.
• Significant cardiac disease
• A marked baseline prolongation of QT/QTc (corrected QT) interval (e.g., repeated demonstration of a QTc interval >480 ms (National Cancer Institute NCI) Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fredericia's QT correction formula.
• A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, clinically significant hypokalemia, family history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval within 14 days of enrollment.
• Positive for HIV or with active hepatitis B or C infection.