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
Advanced Solid TumorLocally Advanced Solid TumorMetastatic Solid TumorPlatinum-resistant Ovarian CancerPost Anti-PD-1 Melanoma2L+ Cervical CancerNeoadjuvant MelanomaNeoadjuvant Non-Small Cell Lung CancerPost Anti-PD-(L)1 Non-Small Cell Lung CancerPost Anti-PD-(L)1 Small Cell Lung CancerThird Line or Later (3L+) HER2+ Breast CancerSecond or Third Line (2L/3L) Cervical CancerThird-line or Later (3L+) Platinum-resistant Ovarian Cancer (PROC)
TransCon IL-2 β/γ: TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
Pembrolizumab: Pembrolizumab will be administered as an intravenous (IV) infusion
Chemotherapy drug: SOC chemotherapy will be administered as an intravenous (IV) infusion
TransCon TLR7/8 Agonist: TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection
Surgery: Surgery will take place 4-6 weeks after last dose of study treatment.
Trastuzumab: Trastuzumab will be administered as an intravenous (IV) infusion
Trastuzumab emtansine (T-DM1): Trastuzumab emtansine (T-DM1) will be administered as an intravenous (IV) infusion
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Safety and Tolerability — Through study completion, expected average of 2 years Treatment emergent and treatment related adverse events (assessed by NCI CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths.
Maximum Tolerated Dose (MTD) — Each cycle is 21 days Determine the maximum tolerated dose by assessing the Incidence of Dose Limiting Toxicities (DLTs), treatment emergent and treatment related adverse events (assessed by NCI CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation and deaths.
Recommended Phase 2 Dose (RP2D) — 12 months To determine a recommended phase 2 dose of TransCon IL-2 β/γ and combination regimen for further development by evaluating number of patients with treatment-related adverse events as assessed by CTCAE.
Trial sites (68)
Facility
City
Region
Status
Ascendis Pharma Investigational Site
Los Angeles
California
Ascendis Pharma Investigational Site
Los Angeles
California
Ascendis Pharma Investigational Site
Springfield
Illinois
Ascendis Pharma Investigational Site
Louisville
Kentucky
Ascendis Pharma Investigational Site
Boston
Massachusetts
Ascendis Pharma Investigational Site
Morristown
New Jersey
Ascendis Pharma Investigational Site
New York
New York
Ascendis Pharma Investigational Site
Huntersville
North Carolina
Ascendis Pharma Investigational Site
Canton
Ohio
Ascendis Pharma Investigational Site
Cincinnati
Ohio
Ascendis Pharma Investigational Site
Oklahoma City
Oklahoma
Ascendis Pharma Investigational Site
Pittsburgh
Pennsylvania
Ascendis Pharma Investigational Site
Nashville
Tennessee
Ascendis Pharma Investigational Site
Richmond
Virginia
Ascendis Pharma Investigational Site
Adelaide
Australia
Ascendis Pharma Investigational Site
Adelaide
Australia
Ascendis Pharma Investigational Site
Brisbane
Australia
Ascendis Pharma Investigational Site
Frankston
Australia
Ascendis Pharma Investigational Site
Southport
Australia
Ascendis Pharma Investigational Site
Toorak Gardens
Australia
Ascendis Pharma Investigational Site
Waratah
Australia
Ascendis Pharma Investigational Site
Wilrijk
Belgium
Ascendis Pharma Investigational Site
Montreal
Canada
Ascendis Pharma Investigational Site
Toronto
Canada
Ascendis Pharma Investigational Site
Toronto
Canada
Ascendis Pharma Investigational Site
Cuneo
Italy
Ascendis Pharma Investigational Site
Florence
Italy
Ascendis Pharma Investigational Site
Grosseto
Italy
Ascendis Pharma Investigational Site
Lido di Camaiore
Italy
Ascendis Pharma Investigational Site
Livorno
Italy
Ascendis Pharma Investigational Site
Meldola
Italy
Ascendis Pharma Investigational Site
Milan
Italy
Ascendis Pharma Investigational Site
Milan
Italy
Ascendis Pharma Investigational Site
Modena
Italy
Ascendis Pharma Investigational Site
Roma
Italy
Ascendis Pharma Investigational Site
Torino
Italy
Ascendis Pharma Investigational Site
Turin
Italy
Ascendis Pharma Investigational Site
Verona
Italy
Ascendis Pharma Investigational Site
Krakow
Poland
Ascendis Pharma Investigational Site
Poznan
Poland
+ 28 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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