Trial record 1 of 82 for:
IL BELIEVE
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)
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| ClinicalTrials.gov Identifier: NCT05081609 |
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Recruitment Status :
Recruiting
First Posted : October 18, 2021
Last Update Posted : April 18, 2023
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Sponsor:
Ascendis Pharma Oncology Division A/S
Information provided by (Responsible Party):
Ascendis Pharma A/S ( Ascendis Pharma Oncology Division A/S )
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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 |
|---|---|---|
| Advanced Solid Tumor Locally Advanced Solid Tumor Metastatic Solid Tumor Platinum-resistant Ovarian Cancer Post Anti-PD-1 Melanoma 2L+ Cervical Cancer Neoadjuvant Melanoma Neoadjuvant Non-Small Cell Lung Cancer | Drug: TransCon IL-2 β/γ Drug: Pembrolizumab Drug: Chemotherapy drug Drug: TransCon TLR7/8 Agonist Procedure: Surgery | Phase 1 Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 317 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | January 11, 2022 |
| Estimated Primary Completion Date : | January 2025 |
| Estimated Study Completion Date : | May 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1 Monotherapy 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
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Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion |
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Experimental: Part 2 Combination 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
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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 |
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Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo
TransCon IL-2 β/γ using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination
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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 |
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Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist
TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination
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Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion Drug: TransCon TLR7/8 Agonist TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection |
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Experimental: Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery
TransCon IL-2 β/γ using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination
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Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion Procedure: Surgery Surgery will take place 4-6 weeks after last dose of study treatment. |
|
Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery
TransCon IL-2 β/γ using the RP2D with Pembrolizumab followed by surgery 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: Pembrolizumab Pembrolizumab will be administered as an intravenous (IV) infusion Procedure: Surgery Surgery will take place 4-6 weeks after last dose of study treatment. |
|
Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery
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
|
Drug: TransCon IL-2 β/γ
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion Drug: 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. |
|
Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery
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
|
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 Drug: Chemotherapy drug SOC chemotherapy will be administered as an intravenous (IV) infusion Procedure: Surgery Surgery will take place 4-6 weeks after last dose of study treatment. |
Primary Outcome Measures :
- Safety and Tolerability [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Average of 2 years ]Response assessed by RECIST v1.1
- Pathologic Complete Response [ Time Frame: 15 weeks ]Evaluate the pathologic Complete Response (pCR) for anti-tumor activity of TransCon IL-2 β/γ alone or in combination with pembrolizumab, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy in the Neoadjuvant Cohorts
- Major Pathologic Response [ Time Frame: 15 weeks ]Evaluate the Major Pathologic Response (MPR) for anti-tumor activity of TransCon IL-2 β/γ alone or in combination with pembrolizumab, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy in the Neoadjuvant Cohorts
- Duration of Response [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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
- Event free survival (EFS) by RECIST 1.1 [ Time Frame: 2 years ]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.
- Overall Survival (OS) [ Time Frame: Average of 2 years ]Time from date of first dose of study treatment to date of death due to any cause
- PK Characterization (Cmax) [ Time Frame: 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 alone or in combination with other therapies
- PK Characterization (Tmax) [ Time Frame: 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 other therapies
- PK Characterization (AUClast) [ Time Frame: 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 other therapies
- PK Characterization (AUC0-t) [ Time Frame: 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 other therapies
- PK Characterization (t1/2) [ Time Frame: 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 other therapies
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05081609
Contacts
| Contact: Ray Tam | 650-374-9144 | RTM@ascendispharma.com |
Locations
| United States, Massachusetts | |
| Ascendis Pharma Investigational Site | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| United States, North Carolina | |
| Ascendis Pharma Investigational Site | Recruiting |
| Huntersville, North Carolina, United States, 28078 | |
| United States, Ohio | |
| Ascendis Pharma Investigational Site | Recruiting |
| Canton, Ohio, United States, 44718 | |
| Ascendis Pharma Investigational Site | Recruiting |
| Cincinnati, Ohio, United States, 45219 | |
| United States, Pennsylvania | |
| Ascendis Pharma Investigational Site | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15232 | |
| United States, Tennessee | |
| Ascendis Pharma Investigational Site | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Australia, Queensland | |
| Ascendis Pharma Investigational Site | Recruiting |
| Southport, Queensland, Australia, 4215 | |
| Australia, South Australia | |
| Ascendis Pharma Investigational Site | Recruiting |
| Adelaide, South Australia, Australia, 5000 | |
| Korea, Republic of | |
| Ascendis Pharma Investigational Site | Recruiting |
| Seoul, Songpa-gu, Korea, Republic of, 05505 | |
Sponsors and Collaborators
Ascendis Pharma Oncology Division A/S
Investigators
| Study Director: | Davis Torrejon-Castro | Ascendis Pharma Oncology Division A/S |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ascendis Pharma Oncology Division A/S |
| ClinicalTrials.gov Identifier: | NCT05081609 |
| Other Study ID Numbers: |
ASND0029 |
| First Posted: | October 18, 2021 Key Record Dates |
| Last Update Posted: | April 18, 2023 |
| Last Verified: | April 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Neoplasms Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Nerve Tissue |
Nevi and Melanomas Pembrolizumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |