IL Believe: A Study of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab or Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 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 |
Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
|
| Experimental: Part 2 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 |
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
|
| Experimental: Part 3 Dose Expansion: TransCon IL-2 β/γ with SOC Chemotherapy TransCon IL-2 β/γ with SOC Chemotherapy using the RP2D from Part 2 to evaluate safety/tolerability and anti-tumor activity of the combination |
Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
Drug: Chemotherapy drug
SOC chemotherapy will be administered as an intravenous (IV) infusion
|
Outcome Measures
Primary Outcome Measures
- 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.
Secondary Outcome Measures
- Overall Response Rate [Average of 2 years]
Response assessed by RECIST v1.1
- Duration of Response [Average of 2 years]
Time from first documentation of objective tumor response (CR or PR that is subsequently confirmed) to first documentation of disease progression or death due to any cause, whichever occurs first
- Time to Response [Expected up to 1 year from first dose]
Time from date of first dose of study treatment to first occurrence of response (CR or PR)
- Progression Free Survival (PFS) [Average of 2 years]
Time from date of first dose of study treatment to first documentation of disease progression or death due to any cause
- Overall Survival (OS) [Average of 2 years]
Time from date of first dose of study treatment to date of death due to any cause
- PK Characterization (Cmax) [Average of 2 years]
Maximum observed plasma concentration of TransCon IL-2 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ
- PK Characterization (Tmax) [Average of 2 years]
Time to reach maximum plasma concentration of TransCon IL-2 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ alone or in combination with pembrolizumab or SOC chemotherapy
- PK Characterization (AUClast) [Average of 2 years]
Area under the plasma concentration curve from time zero to last sampling time at which the concentration is at or above the lower limit of quantification for TransCon IL-2 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ alone or in combination with pembrolizumab or SOC chemotherapy
- PK Characterization (AUC0-t) [Average of 2 years]
Area under the plasma concentration curve from time zero to time t for TransCon IL-2 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ alone or in combination with pembrolizumab or SOC chemotherapy
- PK Characterization (t1/2) [Average of 2 years]
Apparent terminal half-life of TransCon IL-2 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ alone or in combination with pembrolizumab or SOC chemotherapy
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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At least 18 years of age
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Participants must have histologically confirmed locally advanced, recurrent, or metastatic solid tumor malignancies that cannot be treated with curative intent (surgery or radiotherapy)
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At least 1 lesion of measurable disease
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Demonstrated adequate organ function at screening
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Life expectancy >12 weeks as determined by the Investigator
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
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Participants who have undergone treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody must have at least 4 weeks from the last dose of antibody and evidence of disease progression per investigator assessment before Cycle 1 Day 1 (C1D1)
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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 well controlled on physiologic endocrine replacement
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Female and male participants of childbearing potential who are sexually active must agree to use highly effective methods of contraception
Key Exclusion Criteria:
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Symptomatic central nervous system metastases
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Active autoimmune diseases, regardless of need for immunosuppressive treatment at the time of screening, with the exception of participants well controlled on physiologic endocrine replacement
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Any uncontrolled bacterial, fungal, viral, or other infection
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Significant cardiac disease
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A marked 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
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Positive for HIV or has known active hepatitis B or C infection
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Known hypersensitivity to any study treatment(s) used in the specific study part/cohort
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Participants who have been previously treated with IL-2 or IL-2 variants
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Systemic immunosuppressive treatment with the exception for patients on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation). Participants cannot start dosing on study until steroid dose is at or lower than 10 mg per day prednisone or equivalent
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Vaccination with live, attenuated vaccines within 4 weeks of C1D1
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Treatment with any other anti-cancer systemic treatment (approved or investigational) or radiation therapy within 4 weeks of first dosing on study is not allowed
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Women who are breastfeeding or have a positive serum pregnancy test during screening or within 72 hours prior to C1D1 are not eligible
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ascendis Pharma Investigational Site | Boston | Massachusetts | United States | 02114 |
| 2 | Ascendis Pharma Investigational Site | Huntersville | North Carolina | United States | 28078 |
| 3 | Ascendis Pharma Investigational Site | Canton | Ohio | United States | 44718 |
| 4 | Ascendis Pharma Investigational Site | Cincinnati | Ohio | United States | 45219 |
| 5 | Ascendis Pharma Investigational Site | Pittsburgh | Pennsylvania | United States | 15232 |
| 6 | Ascendis Pharma Investigational Site | Southport | Queensland | Australia | 4215 |
Sponsors and Collaborators
- Ascendis Pharma Oncology Division A/S
Investigators
- Study Director: Davis T Castro, Ascendis Pharma Oncology Division A/S
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ASND0029