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

Conditions: Advanced Solid Tumor; Locally Advanced Solid Tumor; Metastatic Solid Tumor; Platinum-resistant Ovarian Cancer; Post Anti-PD-1 Melanoma; 2L+ Cervical Cancer; Neoadjuvant Melanoma; Neoadjuvant Non-Small Cell Lung Cancer; Post Anti-PD-(L)1 Non-Small Cell Lung Cancer; Post Anti-PD-(L)1 Small Cell Lung Cancer; Third Line or Later (3L+) HER2+ Breast Cancer; Second or Third Line (2L/3L) Cervical Cancer; Third-line or Later (3L+) Platinum-resistant Ovarian Cancer (PROC)

Summary: transcon il-2 β/γ is an investigational drug being developed for treatment of locally advanced or metastatic solid tumors. this is a first-in-human, open-label, phase 1/2, dose escalation and dose expansion study of transcon il-2 β/γ as monotherapy or in combination therapy in adult participants with advanced or metastatic solid tumors. given the unique pk profile enabled by the transcon technology, transcon il-2 β/γ presents the opportunity to enhance the therapeutic index of current il-2 therapy.

il-2 is a key cytokine that directs the immune system through pleiotropic effects mediated by promoting expansion of both cytotoxic effector cells and tregs. transcon il-2 β/γ is designed as a long-acting delivery prodrug of il-2 β/γ, a potent cytokine signaling molecule, with the potential to improve the safety and efficacy of il-2.

Eligibility criteria:
key inclusion criteria: * 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 key exclusion criteria: * 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