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

NCT05081609
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Phase
Phase 1/Phase 2
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Recruitment status
Active, not recruiting
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Participants
320
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Lead sponsor
Ascendis Pharma Oncology Division A/S
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Start date
2022-01-11
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Number of sites
68
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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.
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Acronym
IL Believe
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Short title
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
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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, TransCon TLR7/8 Agonist, or Other Anticancer Therapies, in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2029-08-01
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First posted
2021-10-18
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Registry last updated
2026-02-24
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Primary completion date
2027-08-01
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Start date
2022-01-11
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Actual participants
320
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Participants
320
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
68
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Registry sponsor category
Industry
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Lead sponsor
Ascendis Pharma Oncology Division A/S
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05081609
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ClinicalTrials.gov ID
NCT05081609
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Safety and Tolerability

    Timeframe: 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.

  2. Maximum Tolerated Dose (MTD)

    Timeframe: 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.

  3. Recommended Phase 2 Dose (RP2D)

    Timeframe: 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.

  1. Overall Response Rate

    Timeframe: Average of 2 years

    Response assessed by RECIST v1.1

  2. Pathologic Complete Response

    Timeframe: 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

  3. Major Pathologic Response

    Timeframe: 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

  4. Duration of Response

    Timeframe: 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

  5. Time to Response

    Timeframe: 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)

  6. Progression Free Survival (PFS)

    Timeframe: 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

  7. Event free survival (EFS) by RECIST 1.1

    Timeframe: 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.

  8. Overall Survival (OS)

    Timeframe: Average of 2 years

    Time from date of first dose of study treatment to date of death due to any cause

  9. PK Characterization (Cmax)

    Timeframe: 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

  10. PK Characterization (Tmax)

    Timeframe: 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

  11. PK Characterization (AUClast)

    Timeframe: 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

  12. PK Characterization (AUC0-t)

    Timeframe: 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

  13. PK Characterization (t1/2)

    Timeframe: 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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
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
Sources for eligibility
clinicaltrials.gov

  • Ascendis Pharma Investigational SiteLos Angeles, United States
  • Ascendis Pharma Investigational SiteLos Angeles, United States
  • Ascendis Pharma Investigational SiteSpringfield, United States
  • Ascendis Pharma Investigational SiteLouisville, United States
  • Ascendis Pharma Investigational SiteBoston, United States
  • Ascendis Pharma Investigational SiteMorristown, United States
  • Ascendis Pharma Investigational SiteNew York, United States
  • Ascendis Pharma Investigational SiteHuntersville, United States
  • Ascendis Pharma Investigational SiteCanton, United States
  • Ascendis Pharma Investigational SiteCincinnati, United States
  • Ascendis Pharma Investigational SiteOklahoma City, United States
  • Ascendis Pharma Investigational SitePittsburgh, United States
  • Ascendis Pharma Investigational SiteNashville, United States
  • Ascendis Pharma Investigational SiteRichmond, United States
  • Ascendis Pharma Investigational SiteAdelaide, Australia
  • Ascendis Pharma Investigational SiteAdelaide, Australia
  • Ascendis Pharma Investigational SiteBrisbane, Australia
  • Ascendis Pharma Investigational SiteFrankston, Australia
  • Ascendis Pharma Investigational SiteSouthport, Australia
  • Ascendis Pharma Investigational SiteToorak Gardens, Australia
  • Ascendis Pharma Investigational SiteWaratah, Australia
  • Ascendis Pharma Investigational SiteWilrijk, Belgium
  • Ascendis Pharma Investigational SiteMontreal, Canada
  • Ascendis Pharma Investigational SiteToronto, Canada
  • Ascendis Pharma Investigational SiteToronto, Canada

And 43 more, listed on the interactive page.

Sources for sites
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Sources for references
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Related records

Drugs (4)

Lead sponsors (1)

Conditions (1)

Targets (18)