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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05081609




Registration number
NCT05081609
Ethics application status
Date submitted
5/10/2021
Date registered
18/10/2021
Date last updated
15/10/2024

Titles & IDs
Public title
A Study to Investigate Safety and Tolerability of TransCon IL-2 ß/? 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
Scientific 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 ß/? 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
Secondary ID [1] 0 0
ASND0029
Universal Trial Number (UTN)
Trial acronym
IL Believe
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Locally Advanced Solid Tumor 0 0
Metastatic Solid Tumor 0 0
Platinum-resistant Ovarian Cancer 0 0
Post Anti-PD-1 Melanoma 0 0
2L+ Cervical Cancer 0 0
Neoadjuvant Melanoma 0 0
Neoadjuvant Non-Small Cell Lung Cancer 0 0
Post Anti-PD-(L)1 Non-Small Cell Lung Cancer 0 0
Post Anti-PD-(L)1 Small Cell Lung Cancer 0 0
Third Line or Later (3L+) HER2+ Breast Cancer 0 0
Second or Third Line (2L/3L) Cervical Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TransCon IL-2 ß/?
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Chemotherapy drug
Treatment: Drugs - TransCon TLR7/8 Agonist
Treatment: Surgery - Surgery
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Trastuzumab emtansine (T-DM1)

Experimental: Part 1 Monotherapy Dose Escalation: TransCon IL-2 ß/? - TransCon IL-2 ß/? in escalating doses to evaluate safety/tolerability and to determine the MTD and RP2D

Experimental: Part 2 Combination Dose Escalation: TransCon IL-2 ß/? with Pembrolizumab - TransCon IL-2 ß/? with Pembrolizumab in escalating doses to evaluate safety/tolerability and determine the MTD and RP2D

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? with SOC Chemo - TransCon IL-2 ß/? using the RP2D with SOC Chemotherapy to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? with TransCon TLR7/8 Agonist - TransCon IL-2 ß/? with TransCon TLR7/8 Agonist using the RP2D to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Monotherapy Dose Expansion: TransCon IL-2 ß/? followed by surgery - (Optional Arm): TransCon IL-2 ß/? using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? with Pembrolizumab followed by surgery - TransCon IL-2 ß/? using the RP2D with Pembrolizumab followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 ß/? with TransCon TLR7/8 Agonist followed by surgery - TransCon IL-2 ß/? with TransCon TLR7/8 Agonist using the RP2D followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion:TransCon IL-2 ß/? + Pembrolizumab + SOC Chemo followed by surgery - TransCon IL-2 ß/? using the RP2D with Pembrolizumab and SOC Chemotherapy followed by surgery to evaluate safety/tolerability and anti-tumor activity of the combination

Experimental: Part 3 Combination Dose Expansion - TransCon IL-2 ß/? + Pembrolizumab TransCon IL-2 ß/? using the RP2D with Pembrolizumab

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? monotherapy - TransCon IL-2 ß/? monotherapy

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? + trastuzumab - TransCon IL-2 ß/? + trastuzumab

Experimental: Part 3 Combination Dose Expansion: TransCon IL-2 ß/? + trastuzumab emtansine (T-DM1) - TransCon IL-2 ß/? + trastuzumab emtansine (T-DM1)

Experimental: Part 4 Combination Dose Optimization - TransCon IL-2 ß/? + Pembrolizumab TransCon IL-2 ß/? using the RP2D in titrating doses and/or different dose frequencies with Pembrolizumab


Treatment: Drugs: TransCon IL-2 ß/?
TransCon IL-2 ß/? will be administered as an intravenous (IV) infusion

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion

Treatment: Drugs: Chemotherapy drug
SOC chemotherapy will be administered as an intravenous (IV) infusion

Treatment: Drugs: TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist will be administered as an IT (Intratumoral) injection

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

Treatment: Drugs: Trastuzumab
Trastuzumab will be administered as an intravenous (IV) infusion

Treatment: Drugs: Trastuzumab emtansine (T-DM1)
Trastuzumab emtansine (T-DM1) will be administered as an intravenous (IV) infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability
Timepoint [1] 0 0
Through study completion, expected average of 2 years
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD)
Timepoint [2] 0 0
Each cycle is 21 days
Primary outcome [3] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [3] 0 0
12 months
Secondary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
Average of 2 years
Secondary outcome [2] 0 0
Pathologic Complete Response
Timepoint [2] 0 0
15 weeks
Secondary outcome [3] 0 0
Major Pathologic Response
Timepoint [3] 0 0
15 weeks
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
Average of 2 years
Secondary outcome [5] 0 0
Time to Response
Timepoint [5] 0 0
Expected up to 1 year from first dose
Secondary outcome [6] 0 0
Progression Free Survival (PFS)
Timepoint [6] 0 0
Average of 2 years
Secondary outcome [7] 0 0
Event free survival (EFS) by RECIST 1.1
Timepoint [7] 0 0
2 years
Secondary outcome [8] 0 0
Overall Survival (OS)
Timepoint [8] 0 0
Average of 2 years
Secondary outcome [9] 0 0
PK Characterization (Cmax)
Timepoint [9] 0 0
Average of 2 years
Secondary outcome [10] 0 0
PK Characterization (Tmax)
Timepoint [10] 0 0
Average of 2 years
Secondary outcome [11] 0 0
PK Characterization (AUClast)
Timepoint [11] 0 0
Average of 2 years
Secondary outcome [12] 0 0
PK Characterization (AUC0-t)
Timepoint [12] 0 0
Average of 2 years
Secondary outcome [13] 0 0
PK Characterization (t1/2)
Timepoint [13] 0 0
Average of 2 years

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2029
Actual
Sample size
Target
473
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Ascendis Pharma Investigational Site - Adelaide
Recruitment hospital [2] 0 0
Ascendis Pharma Investigational Site - Frankston
Recruitment hospital [3] 0 0
Ascendis Pharma Investigational Site - Southport
Recruitment hospital [4] 0 0
Ascendis Pharma Investigational Site - Toorak Gardens
Recruitment hospital [5] 0 0
Ascendis Pharma Investigational Site - Waratah
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
05065 - Toorak Gardens
Recruitment postcode(s) [6] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oklahoma
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Belgium
State/province [10] 0 0
Wilrijk
Country [11] 0 0
Canada
State/province [11] 0 0
Montréal
Country [12] 0 0
Canada
State/province [12] 0 0
Toronto
Country [13] 0 0
Italy
State/province [13] 0 0
Firenze
Country [14] 0 0
Italy
State/province [14] 0 0
Grosseto
Country [15] 0 0
Italy
State/province [15] 0 0
Lido Di Camaiore
Country [16] 0 0
Italy
State/province [16] 0 0
Livorno
Country [17] 0 0
Italy
State/province [17] 0 0
Meldola
Country [18] 0 0
Italy
State/province [18] 0 0
Milan
Country [19] 0 0
Italy
State/province [19] 0 0
Roma
Country [20] 0 0
Italy
State/province [20] 0 0
Turin
Country [21] 0 0
Italy
State/province [21] 0 0
Verona
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Songpa-gu
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seongnam-si
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Poland
State/province [25] 0 0
Kraków
Country [26] 0 0
Poland
State/province [26] 0 0
Poznan
Country [27] 0 0
Poland
State/province [27] 0 0
Warszawa
Country [28] 0 0
Singapore
State/province [28] 0 0
Singapore
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Murcia
Country [32] 0 0
Spain
State/province [32] 0 0
Málaga
Country [33] 0 0
Spain
State/province [33] 0 0
Oviedo
Country [34] 0 0
Spain
State/province [34] 0 0
Pamplona
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Spain
State/province [36] 0 0
Valencia
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ascendis Pharma Oncology Division A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
TransCon IL-2 ß/? 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 ß/? 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 ß/? presents the opportunity to enhance the therapeutic index of current IL-2 therapy.
Trial website
https://clinicaltrials.gov/study/NCT05081609
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Davis Torrejon-Castro
Address 0 0
Medical Monitor
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ascendis Oncology Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
+1 650-352-8389
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05081609