Advanced Solid TumorPhase 1/2IL BelieveNCT05081609
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
A Phase 1/2 study testing TransCon IL-2 β/γ, Pembrolizumab and Chemotherapy drug in people with Advanced Solid Tumor and Locally Advanced Solid Tumor, run by Ascendis Pharma Oncology Division A/S at 68 sites in 10 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Locally Advanced Solid Tumor, Metastatic Solid Tumor
- What is being tested?
- TransCon IL-2 β/γ, Pembrolizumab and Chemotherapy drug
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 68 sitesin 10 countries
- Study dates
- 11 Jan 2022to Aug 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
68 sites in 10 countries.
68 sites in 10 countries
Spain17 sites
Ascendis Pharma Investigational Site
Barcelona, 08023
Ascendis Pharma Investigational Site
Barcelona, 08028
Ascendis Pharma Investigational Site
Barcelona, 08035
Ascendis Pharma Investigational Site
L'Hospitalet de Llobregat, 08908
Ascendis Pharma Investigational Site
Madrid, 28006
Ascendis Pharma Investigational Site
Madrid, 28027
Ascendis Pharma Investigational Site
Madrid, 28040
Ascendis Pharma Investigational Site
Madrid, 28041
Ascendis Pharma Investigational Site
Madrid, 28050
Ascendis Pharma Investigational Site
Málaga, 29010
Ascendis Pharma Investigational Site
Murcia, 30120
Ascendis Pharma Investigational Site
Oviedo, 33011
Ascendis Pharma Investigational Site
Pamplona, 31008
Ascendis Pharma Investigational Site
Seville, 41009
Ascendis Pharma Investigational Site
Seville, 41014
Ascendis Pharma Investigational Site
Valencia, 46009
Ascendis Pharma Investigational Site
Valencia, 46014
United States14 sites
Ascendis Pharma Investigational Site
Boston, Massachusetts, 02114
Ascendis Pharma Investigational Site
Canton, Ohio, 44718
Ascendis Pharma Investigational Site
Cincinnati, Ohio, 45219
Ascendis Pharma Investigational Site
Huntersville, North Carolina, 28078
Ascendis Pharma Investigational Site
Los Angeles, California, 90048
Ascendis Pharma Investigational Site
Los Angeles, California, 90067
Ascendis Pharma Investigational Site
Louisville, Kentucky, 40202
Ascendis Pharma Investigational Site
Morristown, New Jersey, 07960
Ascendis Pharma Investigational Site
Nashville, Tennessee, 37203
Ascendis Pharma Investigational Site
New York, New York, 10032
Ascendis Pharma Investigational Site
Oklahoma City, Oklahoma, 73104
Ascendis Pharma Investigational Site
Pittsburgh, Pennsylvania, 15232
Ascendis Pharma Investigational Site
Richmond, Virginia, 23298
Ascendis Pharma Investigational Site
Springfield, Illinois, 62702
Italy13 sites
Ascendis Pharma Investigational Site
Cuneo, 12100
Ascendis Pharma Investigational Site
Florence, 50134
Ascendis Pharma Investigational Site
Grosseto, 58100
Ascendis Pharma Investigational Site
Lido di Camaiore, 55041
Ascendis Pharma Investigational Site
Livorno, 57124
Ascendis Pharma Investigational Site
Meldola, 47014
Ascendis Pharma Investigational Site
Milan, 20133
Ascendis Pharma Investigational Site
Milan, 20141
Ascendis Pharma Investigational Site
Modena, 41124
Ascendis Pharma Investigational Site
Roma, 00167
Ascendis Pharma Investigational Site
Torino, 10126
Ascendis Pharma Investigational Site
Turin, 10060
Ascendis Pharma Investigational Site
Verona, 37134
Australia7 sites
Ascendis Pharma Investigational Site
Adelaide, 5000
Ascendis Pharma Investigational Site
Adelaide, 5042
Ascendis Pharma Investigational Site
Brisbane, 04120
Ascendis Pharma Investigational Site
Frankston, 3199
Ascendis Pharma Investigational Site
Southport, 4215
Ascendis Pharma Investigational Site
Toorak Gardens, 05065
Ascendis Pharma Investigational Site
Waratah, 2298
South Korea6 sites
Ascendis Pharma Investigational Site
Seongnam-si, 13620
Ascendis Pharma Investigational Site
Seoul, Songpa-gu, 05505
Ascendis Pharma Investigational Site
Seoul, 03080
Ascendis Pharma Investigational Site
Seoul, 03722
Ascendis Pharma Investigational Site
Seoul, 06231
Ascendis Pharma Investigational Site
Seoul, 06351
Canada3 sites
Ascendis Pharma Investigational Site
Montreal, H4A 3J1
Ascendis Pharma Investigational Site
Toronto, M4N 3M5
Ascendis Pharma Investigational Site
Toronto, M5G 2C4
Poland3 sites
Ascendis Pharma Investigational Site
Krakow, 31-501
Ascendis Pharma Investigational Site
Poznan, 60693
Ascendis Pharma Investigational Site
Warsaw, 02-781
Singapore2 sites
Ascendis Pharma Investigational Site
Singapore, 119228
Ascendis Pharma Investigational Site
Singapore, 217562
Taiwan2 sites
Ascendis Pharma Investigational Site
Taipei, 10002
Ascendis Pharma Investigational Site
Taipei, 11259
About this study
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
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.
Read the 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.
- Conditions
- Advanced Solid Tumor, Locally Advanced Solid Tumor, Metastatic Solid Tumor, Platinum-resistant Ovarian Cancer, Post Anti-PD-1 Melanoma, 2L+ Cervical Cancer
- Being tested
- TransCon IL-2 β/γ, Pembrolizumab, Chemotherapy drug, TransCon TLR7/8 Agonist, Surgery
- Medical subject headings
- Neoplasm Metastasis, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TransCon IL-2 β/γDrug
TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
PembrolizumabDrug
Pembrolizumab will be administered as an intravenous (IV) infusion
Chemotherapy drugDrug
SOC chemotherapy will be administered as an intravenous (IV) infusion
TransCon TLR7/8 AgonistDrug
TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection
SurgeryProcedure or surgery
Surgery will take place 4-6 weeks after last dose of study treatment.
TrastuzumabDrug
Trastuzumab will be administered as an intravenous (IV) infusion
Trastuzumab emtansine (T-DM1)Drug
Trastuzumab emtansine (T-DM1) will be administered as an intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Monotherapy Dose Escalation: TransCon IL-2 β/γ | Experimental | TransCon IL-2 β/γ in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D Receives: Drug: TransCon IL-2 β/γ |
| Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with Pembrolizumab | Experimental | TransCon IL-2 β/γ with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D Receives: Drug: TransCon IL-2 β/γ; Drug: Pembrolizumab |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo | Experimental | TransCon IL-2 β/γ using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination Receives: Drug: TransCon IL-2 β/γ; Drug: Chemotherapy drug |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist | Experimental | TransCon IL-2 β/γ with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination Receives: Drug: TransCon IL-2 β/γ; Drug: TransCon TLR7/8 Agonist |
| Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery | Experimental | (Optional Arm): TransCon IL-2 β/γ using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination Receives: Drug: TransCon IL-2 β/γ; Procedure: Surgery |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery | Experimental | TransCon IL-2 β/γ using the RP2D with Pembrolizumab followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination Receives: Drug: TransCon IL-2 β/γ; Drug: Pembrolizumab; Procedure: Surgery |
| Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery | Experimental | 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 Receives: Drug: TransCon IL-2 β/γ; Drug: TransCon TLR7/8 Agonist; Procedure: Surgery |
| Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery | Experimental | 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 Receives: Drug: TransCon IL-2 β/γ; Drug: Pembrolizumab; Drug: Chemotherapy drug; Procedure: Surgery |
| Part 3 Combination Dose Expansion | Experimental | TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D with Pembrolizumab Receives: Drug: TransCon IL-2 β/γ; Drug: Pembrolizumab |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapy | Experimental | TransCon IL-2 β/γ monotherapy Receives: Drug: TransCon IL-2 β/γ |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab | Experimental | TransCon IL-2 β/γ + trastuzumab Receives: Drug: TransCon IL-2 β/γ; Drug: Trastuzumab |
| Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1) | Experimental | TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1) Receives: Drug: TransCon IL-2 β/γ; Drug: Trastuzumab emtansine (T-DM1) |
| Part 4 Combination Dose Optimization | Experimental | TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D in titrating doses and/or different dose frequencies with Pembrolizumab Receives: Drug: TransCon IL-2 β/γ; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, expected average of 2 years
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.
Measured: Each cycle is 21 days
Recommended Phase 2 Dose (RP2D)
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.
Measured: 12 months
Secondary outcomes (13)
Overall Response Rate
Response assessed by RECIST v1.1
Measured: Average of 2 years
Pathologic Complete Response
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
Measured: 15 weeks
Major Pathologic Response
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
Measured: 15 weeks
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
Measured: Average of 2 years
Time to Response
Time from date of first dose of study treatment to first occurrence of response (CR or PR)
Measured: Expected up to 1 year from first dose
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
Measured: Average of 2 years
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.
Measured: 2 years
Overall Survival (OS)
Time from date of first dose of study treatment to date of death due to any cause
Measured: Average of 2 years
PK Characterization (Cmax)
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
Measured: Average of 2 years
PK Characterization (Tmax)
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
Measured: Average of 2 years
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 β/γ and Free IL-2 β/γ after IV administration of TransCon IL-2 β/γ alone or in combination with other therapies
Measured: Average of 2 years
PK Characterization (AUC0-t)
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
Measured: Average of 2 years
PK Characterization (t1/2)
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
Measured: Average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start11 Jan 2022
- Primary completionAug 2027 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascendis Pharma Oncology Division A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Davis Torrejon-Castro, Study director, Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05081609
- Sponsor's protocol ID
- ASND0029
- Acronym
- IL Believe
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2021
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rosen DB, Kvarnhammar AM, Laufer B, Knappe T, Karlsson JJ, Hong E, Lee YC, Thakar D, Zuniga LA, Bang K, Sabharwal SS, Uppal K, Olling JD, Kjaergaard K, Kurpiers T, Schnabel M, Reich D, Glock P, Zettler J, Krusch M, Bernhard A, Heinig S, Konjik V, Wegge T, Hehn Y, Killian S, Viet L, Runz J, Faltinger F, Tabrizi M, Abel KL, Breinholt VM, Singel SM, Sprogoe K, Punnonen J. TransCon IL-2 beta/gamma: a novel long-acting prodrug with sustained release of an IL-2Rbeta/gamma-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer. J Immunother Cancer. 2022 Jul;10(7):e004991. doi: 10.1136/jitc-2022-004991.
PubMed 35817480