NCT05081609|Active Not RecruitingPhase 1FDA Drug

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

IL Believe

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

Ascendis Pharma Oncology Division A/S ClinicalTrials.gov

Compare

1 other identifier

ASND0029

Study Type

interventional

Target

320

Locations

10 countries

Sites

Timeline

RegisteredOct 2021

StartedJan 2022

CompletionAug 2029

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

320

participants targeted

Target at P75+ for phase_1

Timeline

39mo left

Started Jan 2022

Longer than P75 for phase_1

Geographic Reach

10 countries

68 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.6 years study duration

Study Progress57%

Jan 2022Aug 2029

First Submitted

Initial submission to the registry

October 5, 2021

Completed

13 days until next milestone

First Posted

Study publicly available on registry

October 18, 2021

Completed

3 months until next milestone

Study Start

First participant enrolled

January 11, 2022

Completed

5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2027

Expected

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2029

Last Updated

February 24, 2026

Status Verified

February 1, 2026

Enrollment Period

5.6 years

First QC Date

October 5, 2021

Last Update Submit

February 23, 2026

Conditions

Third-line or Later (3L+) Platinum-resistant Ovarian Cancer (PROC)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 Post Anti-PD-(L)1 Non-Small Cell Lung Cancer Post Anti-PD-(L)1 Small Cell Lung Cancer Third Line or Later (3L+) HER2+ Breast Cancer Second or Third Line (2L/3L) Cervical Cancer

Outcome Measures

Primary Outcomes (3)

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
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
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.
12 months

Secondary Outcomes (13)

Overall Response Rate
Average of 2 years
Pathologic Complete Response
15 weeks
Major Pathologic Response
15 weeks
Duration of Response
Average of 2 years
Time to Response
Expected up to 1 year from first dose
+8 more secondary outcomes

Study Arms (13)

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

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

Drug: TransCon IL-2 β/γDrug: 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

Drug: TransCon IL-2 β/γDrug: 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

Drug: TransCon IL-2 β/γDrug: 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

Drug: TransCon IL-2 β/γProcedure: 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

Drug: TransCon IL-2 β/γDrug: PembrolizumabProcedure: 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

Drug: TransCon IL-2 β/γDrug: TransCon TLR7/8 AgonistProcedure: 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

Drug: TransCon IL-2 β/γDrug: PembrolizumabDrug: Chemotherapy drugProcedure: Surgery

Part 3 Combination Dose Expansion

EXPERIMENTAL

TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D with Pembrolizumab

Drug: TransCon IL-2 β/γDrug: Pembrolizumab

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapy

EXPERIMENTAL

TransCon IL-2 β/γ monotherapy

Drug: TransCon IL-2 β/γ

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab

EXPERIMENTAL

TransCon IL-2 β/γ + trastuzumab

Drug: TransCon IL-2 β/γDrug: 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)

Drug: TransCon IL-2 β/γDrug: 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

Drug: TransCon IL-2 β/γDrug: Pembrolizumab

Interventions

TransCon TLR7/8 AgonistDRUG

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

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 AgonistPart 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery

TrastuzumabDRUG

Trastuzumab will be administered as an intravenous (IV) infusion

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab

Trastuzumab emtansine (T-DM1)DRUG

Trastuzumab emtansine (T-DM1) will be administered as an intravenous (IV) infusion

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)

TransCon IL-2 β/γDRUG

TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion

Part 1 Monotherapy Dose Escalation: TransCon IL-2 β/γPart 2 Combination Dose Escalation: TransCon IL-2 β/γ with PembrolizumabPart 3 Combination Dose ExpansionPart 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumabPart 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapyPart 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgeryPart 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC ChemoPart 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 AgonistPart 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgeryPart 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgeryPart 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgeryPart 4 Combination Dose Optimization

PembrolizumabDRUG

Pembrolizumab will be administered as an intravenous (IV) infusion

Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with PembrolizumabPart 3 Combination Dose ExpansionPart 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgeryPart 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgeryPart 4 Combination Dose Optimization

Chemotherapy drugDRUG

SOC chemotherapy will be administered as an intravenous (IV) infusion

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC ChemoPart 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery

SurgeryPROCEDURE

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

Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgeryPart 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgeryPart 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgeryPart 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.