A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies

Age

18–any

Sex

ALL

Healthy volunteers

Not accepted

At least 18 years of age, or country defined local legal age
Demonstrated adequate organ function at screening
Life expectancy \>12 weeks as determined by the Investigator
Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception
Participants must have histologically confirmed locally advanced, recurrent, or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy), with the exception of the neoadjuvant cohorts
Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Part 3 and Part 4: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated protein (CTLA-4) antibody must have a washout of at least 4 weeks from the last dose and evidence of disease progression per investigator assessment before Cycle 1 Day 1 (C1D1) with the exception of the neoadjuvant cohorts
Participants who have previously received an immunotherapy prior to C1D1 must have any immune-related toxicities resolved to ≤Grade 1 or baseline (prior to the immunotherapy) to be eligible, with the exception of participants on well controlled physiologic endocrine replacement
Part 3: Neoadjuvant cohorts: participants must have completely resectable disease

Symptomatic central nervous system metastases and/or carcinomatous meningitis
Active autoimmune diseases, regardless of need for immunosuppressive treatment, with the exception of participants well controlled on physiologic endocrine replacement
Any uncontrolled bacterial, fungal, viral, or other infection
Significant cardiac disease
A marked clinically significant baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>480 ms) \[CTCAE Grade 1\]) using Fridericia's QT correction formula
Positive for human immunodeficiency virus (HIV) or has known active hepatitis B or C infection
Known hypersensitivity to any study treatment(s) used in the specific study part/cohort
Participants who have been previously treated with IL-2 or IL-2 variants (all participants)
Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation).
Vaccination with live, attenuated vaccines within 4 weeks of C1D1
Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of C1D1
Part 3: Other active malignancies within the last 2 years
Women who are breastfeeding or have a positive serum pregnancy test during screening