Clinical Trial Finder

Key

Inclusion Criteria:

• - At least 18 years of 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.

• - Part 3, Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, and Neoadjuvant Melanoma: Participants who have been previously treated with IL-2 or IL-2 variants (all participants), or TLR agonist.

• - 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

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.

Arms

Experimental: Part 1 Monotherapy Dose Escalation: TransCon IL-2 β/γ

TransCon IL-2 β/γ in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D

Experimental: Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with Pembrolizumab

TransCon IL-2 β/γ with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo

TransCon IL-2 β/γ using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist

TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery

(Optional Arm): TransCon IL-2 β/γ using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery

TransCon IL-2 β/γ using the RP2D with Pembrolizumab followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery

TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery

TransCon IL-2 β/γ using the RP2D with Pembrolizumab and SOC Chemotherapy followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion

TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D with Pembrolizumab

Experimental: Part 4 Combination Dose Optimization

TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D in titrating doses and/or different dose frequencies with Pembrolizumab

Interventions

Drug: - TransCon IL-2 β/γ

TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion

Drug: - Pembrolizumab

Pembrolizumab will be administered as an intravenous (IV) infusion

Drug: - Chemotherapy drug

SOC chemotherapy will be administered as an intravenous (IV) infusion

Drug: - TransCon TLR7/8 Agonist

TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection

Procedure: - Surgery

Surgery will take place 4-6 weeks after last dose of study treatment.