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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

PHASE1PHASE2RECRUITING

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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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-01-11

Primary completion: 2027-08-01

Study completion finish: 2029-08-01

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05081609

Intervention or treatment

DRUG: TransCon IL-2 β/γ

DRUG: Pembrolizumab

DRUG: Chemotherapy drug

DRUG: TransCon TLR7/8 Agonist

PROCEDURE: Surgery

DRUG: Trastuzumab

DRUG: Trastuzumab emtansine (T-DM1)

Conditions

• 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

Condition: Advanced Solid Tumor, Locally Advanced Solid Tumor and more
DRUG: TransCon IL-2 β/γ and other drugs
Adelaide, Not Specified, Australia and more
Sponsor: Ascendis Pharma Oncology Division A/S

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Find a site

Closest Location:

Ascendis Pharma Investigational Site

Research sites nearby

Select from list below to view details:

Ascendis Pharma Investigational Site
Adelaide, Not Specified, Australia
Ascendis Pharma Investigational Site
Adelaide, Not Specified, Australia
Ascendis Pharma Investigational Site
Frankston, Not Specified, Australia
Ascendis Pharma Investigational Site
Southport, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
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	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
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	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
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	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
EXPERIMENTAL: Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery (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/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
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
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
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
EXPERIMENTAL: Part 3 Combination Dose Expansion TransCon IL-2 β/γ + Pembrolizumab TransCon IL-2 β/γ using the RP2D with Pembrolizumab	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapy TransCon IL-2 β/γ monotherapy	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab TransCon IL-2 β/γ + trastuzumab	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1) TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)	DRUG: TransCon IL-2 β/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion
EXPERIMENTAL: Part 4 Combination Dose Optimization 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/γ TransCon IL-2 β/γ will be administered as an intravenous (IV) infusion

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Overall Response Rate	Response assessed by RECIST v1.1	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	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	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	Average of 2 years
Time to Response	Time from date of first dose of study treatment to first occurrence of response (CR or PR)	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	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.	2 years
Overall Survival (OS)	Time from date of first dose of study treatment to date of death due to any cause	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	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	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	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	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	Average of 2 years

Frequently Asked Questions

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References

Clinical Trials Gov: 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