Active, not recruiting
Phase 1/Phase 2
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
Condition(s) studied
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)
Investigational drug(s) / intervention(s)
TransCon IL-2 β/γPembrolizumabChemotherapy drugTransCon TLR7/8 AgonistSurgeryTrastuzumabTrastuzumab emtansine (T-DM1)
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
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.