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

Advanced Solid Tumor Clinical Trial

— IL Believe  

Official title:

IL Believe: A Phase 1/2, Open-label, Dose Escalation and Dose Expansion Study to Investigate the Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab, Standard of Care Chemotherapy, or TransCon TLR7/8 Agonist, or in Combination With Pembrolizumab and Standard of Care Chemotherapy, in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05081609
• Other study ID #: ASND0029
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 11, 2022
• Est. completion date: August 2027

Study information

• Verified date: December 2023
• Source: Ascendis Pharma A/S
• Contact: Ray Tam
• Phone: 650-374-9144
• Email: RTM[@]ascendispharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 393
• Est. completion date: August 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Locally Advanced Solid Tumor
• Lung Neoplasms
• Melanoma
• Metastatic Solid Tumor
• Neoplasms
• Platinum-resistant Ovarian Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• TransCon IL-2 ß/?
TransCon IL-2 ß/? 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

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

Locations

Country	Name	City	State
Australia	Ascendis Pharma Investigational Site	Adelaide	South Australia
Australia	Ascendis Pharma Investigational Site	Southport	Queensland
Korea, Republic of	Ascendis Pharma Investigational Site	Seoul	Songpa-gu
United States	Ascendis Pharma Investigational Site	Boston	Massachusetts
United States	Ascendis Pharma Investigational Site	Canton	Ohio
United States	Ascendis Pharma Investigational Site	Cincinnati	Ohio
United States	Ascendis Pharma Investigational Site	Huntersville	North Carolina
United States	Ascendis Pharma Investigational Site	Nashville	Tennessee
United States	Ascendis Pharma Investigational Site	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Ascendis Pharma Oncology Division A/S

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	Treatment emergent and treatment related adverse events (assessed by NCI CTCAE v5.0), serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths.	Through study completion, expected average of 2 years
Primary	Maximum Tolerated Dose (MTD)	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.	Each cycle is 21 days
Primary	Recommended Phase 2 Dose (RP2D)	To determine a recommended phase 2 dose of TransCon IL-2 ß/? and combination regimen for further development by evaluating number of patients with treatment-related adverse events as assessed by CTCAE.	12 months
Secondary	Overall Response Rate	Response assessed by RECIST v1.1	Average of 2 years
Secondary	Pathologic Complete Response	Evaluate the pathologic Complete Response (pCR) for anti-tumor activity of TransCon IL-2 ß/? alone or in combination with pembrolizumab, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy in the Neoadjuvant Cohorts	15 weeks
Secondary	Major Pathologic Response	Evaluate the Major Pathologic Response (MPR) for anti-tumor activity of TransCon IL-2 ß/? alone or in combination with pembrolizumab, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy in the Neoadjuvant Cohorts	15 weeks
Secondary	Duration of Response	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	Average of 2 years
Secondary	Time to Response	Time from date of first dose of study treatment to first occurrence of response (CR or PR)	Expected up to 1 year from first dose
Secondary	Progression Free Survival (PFS)	Time from date of first dose of study treatment to first documentation of disease progression or death due to any cause	Average of 2 years
Secondary	Event free survival (EFS) by RECIST 1.1	Time from the date of the first dose of study treatment to the occurrence of any of the following: progression of disease that precludes surgery, disease recurrence after surgery, or death from any cause.	2 years
Secondary	Overall Survival (OS)	Time from date of first dose of study treatment to date of death due to any cause	Average of 2 years
Secondary	PK Characterization (Cmax)	Maximum observed plasma concentration of TransCon IL-2 ß/? and Free IL-2 ß/? after IV administration of TransCon IL-2 ß/? alone or in combination with other therapies	Average of 2 years
Secondary	PK Characterization (Tmax)	Time to reach maximum plasma concentration of TransCon IL-2 ß/? and Free IL-2 ß/? after IV administration of TransCon IL-2 ß/? alone or in combination other therapies	Average of 2 years
Secondary	PK Characterization (AUClast)	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 ß/? and Free IL-2 ß/? after IV administration of TransCon IL-2 ß/? alone or in combination with other therapies	Average of 2 years
Secondary	PK Characterization (AUC0-t)	Area under the plasma concentration curve from time zero to time t for TransCon IL-2 ß/? and Free IL-2 ß/? after IV administration of TransCon IL-2 ß/? alone or in combination with other therapies	Average of 2 years
Secondary	PK Characterization (t1/2)	Apparent terminal half-life of TransCon IL-2 ß/? and Free IL-2 ß/? after IV administration of TransCon IL-2 ß/? alone or in combination with other therapies	Average of 2 years