A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or Chemotherapy or TransCon TLR7/8 Agonist in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (IL Believe)
Advanced Solid Tumor, Locally Advanced Solid Tumor, Metastatic Solid Tumor
About this trial
This is an interventional treatment trial for Advanced Solid Tumor
Eligibility Criteria
Key Inclusion Criteria:
- At least 18 years of age
- Demonstrated adequate organ function at screening
- Life expectancy >12 weeks as determined by the Investigator
- At least 1 lesion of measurable disease, except for Post Anti-PD-1 Melanoma and 2L+ Cervical Cancer (at least 2 lesions of measurable disease)
- 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: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Part 1 and Part 2: Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-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)
- Part 1 and Part 2: 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: Part 3, neoadjuvant cohorts: participants must have completely resectable disease
Key Exclusion Criteria:
- Symptomatic central nervous system metastases
- 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 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), or TLR agonist (Part 3 only for Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer, and Neoadjuvant Melanoma)
- 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
Sites / Locations
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
- Ascendis Pharma Investigational SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Part 1 Monotherapy Dose Escalation: TransCon IL-2 β/γ
Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with Pembrolizumab
Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo
Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist
Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery
Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery
Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery
Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery
TransCon IL-2 β/γ in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D
TransCon IL-2 β/γ with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D
TransCon IL-2 β/γ using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination
TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination
TransCon IL-2 β/γ using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination
TransCon IL-2 β/γ using the RP2D with Pembrolizumab followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination
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
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