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
PHASE1PHASE2ACTIVE_NOT_RECRUITING
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.
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.
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
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study 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
- Third-line or Later (3L+) Platinum-resistant Ovarian Cancer (PROC)
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Ascendis Pharma Investigational Site
Select from list below to view details:
Ascendis Pharma Investigational Site
Adelaide, Australia
Ascendis Pharma Investigational Site
Adelaide, Australia
Ascendis Pharma Investigational Site
Brisbane, Australia
Ascendis Pharma Investigational Site
Frankston, Australia
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Who is running the clinical trial?
APODA
Ascendis Pharma Oncology Division A/S
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
| Drug: TransCon IL-2 β/γ |
EXPERIMENTAL: Part 2 Combination Dose Escalation: TransCon IL-2 β/γ with Pembrolizumab
| Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with SOC Chemo
| Drug: TransCon IL-2 β/γ, Drug: Chemotherapy drug |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with TransCon TLR7/8 Agonist
| Drug: TransCon IL-2 β/γ, Drug: TransCon TLR7/8 Agonist |
EXPERIMENTAL: Part 3 Monotherapy Dose Expansion: TransCon IL-2 β/γ followed by surgery
| Drug: TransCon IL-2 β/γ, Procedure: Surgery |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ with Pembrolizumab followed by surgery
| Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab, Procedure: Surgery |
EXPERIMENTAL: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ with TransCon TLR7/8 Agonist followed by surgery
| Drug: TransCon IL-2 β/γ, Drug: TransCon TLR7/8 Agonist, Procedure: Surgery |
EXPERIMENTAL: Part 3 Combination Dose Expansion:TransCon IL-2 β/γ + Pembrolizumab + SOC Chemo followed by surgery
| Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab, Drug: Chemotherapy drug, Procedure: Surgery |
EXPERIMENTAL: Part 3 Combination Dose Expansion
| Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ monotherapy
| Drug: TransCon IL-2 β/γ |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab
| Drug: TransCon IL-2 β/γ, Drug: Trastuzumab |
EXPERIMENTAL: Part 3 Combination Dose Expansion: TransCon IL-2 β/γ + trastuzumab emtansine (T-DM1)
| Drug: TransCon IL-2 β/γ, Drug: Trastuzumab emtansine (T-DM1) |
EXPERIMENTAL: Part 4 Combination Dose Optimization
| Drug: TransCon IL-2 β/γ, Drug: Pembrolizumab |
What is the study measuring?
Primary Outcome
| Measure | Description | 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
| Measure | Description | 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 |
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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 MalignanciesOther trials to consider
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