locally advanced or metastatic solid tumor malignancies, platinum resistant ovarian cancer, post-anti-pd-1 melanoma, second line or later cervical cancer, neoadjuvant melanoma and neoadjuvant non-small cell lung cancer MedDRA version: 24.1 Level: PT Classification code 10085681 Term: Carbohydrate antigen 242 System Organ Class: 10022891 - Investigations
Conditions
Interventions
Product Name: TransCon IL-2 ß/?
Product Code: ACP-016
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TransCon IL-2 ß/?
Current Sponsor code: ACP-016
Concentration unit
Sponsors
Ascendis Pharma Oncology Division A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Participants must be at least 18 years of age at the time of signing the informed consent; -Capable of giving signed informed consent; -Archival or newly obtained formalin-fixed tissue of tumor specimen: -Part 3, Cohort 3, 4 and 5: A tumor biopsy sample must be provided at baseline unless deemed unfeasible. A fresh biopsy is preferred, but archival tissue is also acceptable. -Part 3, Cohorts 6a-c and 7: archival tissue or newly obtained formalin-fixed tumor tissue; -Demonstrated adequate organ function at screening drawn within 28 days prior to C1D1; -Life expectancy >12 weeks as determined by the Investigator; -For women of childbearing potential: agreement to remain abstinent. -Part 3 ECOG: 0 or 1 Cohort 3, -Histologic or cytologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Carcinosarcoma, sarcoma, mucinous ovarian cancer, or low-grade serous histologies are excluded; -Must have platinum-resistant ovarian cancer; -participants must be appropriate candidates for treatment with single agent paclitaxel, docetaxel, or pemetrexed at study entry based on treating investigator’s clinical assessment; -At least 1 measurable target lesion as per RECIST 1:1. Cohort 4: -Histologically or cytologically confirmed diagnosis of unresectable (stage III) or metastatic (stage IV) cutaneous melanoma who have progressed on anti-PD-1 therapy or had recurrence =65 years) yes F.1.3.1 Number of subjects for this ag
Exclusion criteria
Exclusion criteria: -Symptomatic central nervous system metastases; -Active autoimmune diseases, -Any uncontrolled bacterial, fungal, viral, or other infection; -Significant cardiac disease; -A marked clinically significant baseline prolongation of QT/QTc interval, using Fridericia’s QT correction formula -Positive for HIV or has known active hepatitis B or C infection; -Known hypersensitivity to any study treatment; - Participants who have been previously treated with IL-2 or IL-2 variants (all participants) or TLR agonist, excluding topical agents for unrelated disease (Part 3, Cohorts 4, 5 and 6 ONLY); - Systemic immunosuppressive treatment with the exception for participants on corticosteroid taper (for example, for chronic obstructive pulmonary disease exacerbation); - Vaccination with live, attenuated vaccines within 4 weeks of C1D1. -Women who are breastfeeding or have a positive serum pregnancy test during screening Exclusion Criteria Specific to Part 3 ONLY -Other active malignancies within the last 2 years. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - The main objective of Part 1 and 2 was to evaluate the safety and tolerability, and define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon IL-2 ß/? alone or in combination with pembrolizumab - The main objective of Part 3 is to evaluate the safety and tolerability of TransCon IL-2 ß/? at RP2D as monotherapy and in combination with pembrolizumab, standard of care (SOC) chemotherapy, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy;Secondary Objective: - To evaluate the antitumor activity of TransCon IL-2 ß/? alone or in combination with pembrolizumab, SOC chemotherapy, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy - To characterize the plasma pharmacokinetics (PK) of TransCon IL-2 ß/? and Free IL-2 ß/? alone or in combination with pembrolizumab, SOC chemotherapy, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy;Primary end point(s): Treatment emergent and treatment related adverse events, serious adverse events (SAEs), adverse events leading to treatment discontinuation, deaths.;Timepoint(s) of evaluation of this end point: Through study completion, expected average of 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 3- cohorts 3,4,5: -Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), duration of response (DoR), and time to response (TTR) per independent central review (ICR) - ORR by RECIST 1.1, DoR, and TTR per investigator assessment - Progression-free survival (PFS) by RECIST 1.1 per ICR - PFS by RECIST 1.1 per investigator assessment - Overall Survival (OS); Part 3, cohorts 6a-c, and Cohort 7 - ORR prior to surgery by RECIST 1.1 per ICR - ORR prior to surgery by RECIST 1.1 per investigator assessment - Pathologic complete response (pCR) per central assessment for pathology review - Major pathologic response (MPR) per central assessment for pathology review - pCR per local assessment for pathology review - MPR per local assessment for pathology review - Event-free survival (EFS) by RECIST 1.1 per ICR - EFS by RECIST 1.1 per investigator assessment - OS -TransCon IL-2 ß/? and free IL-2 ß/? PK parameters, alone or in combination with pembrolizumab, SOC chemotherapy, or TransCon TLR7/8 Agonist, or in combination with pembrolizumab and SOC chemotherapy;Timepoint(s) of evaluation of this end point: 1.Overall Response Rate-Time Frame: Average of 2 years 2.Pathologic Complete Response-Time Frame: 15 weeks 3.Major Pathologic Response-Time Frame: 15 weeks 4.Duration of Response-Time Frame: Average of 2 years 5.Time to Response-Time Frame: Expected up to 1 year from first dose 6.Progression Free Survival (PFS)-Time Frame: Average of 2 years 7.Event free survival (EFS) by RECIST 1.1-Time Frame: 2 years 8.Overall Survival (OS) -Time Frame: Average of 2 years 9.PK Characterization (Cmax) -Time Frame: Average of 2 years 10.PK Characterization (Tmax) -Time Frame: Average of 2 years 11.PK Characterization (AUClast) -Time Frame: Average of 2 years 12.PK Characterization (AUC0-t) -Time Frame: Average of 2 years 13.PK Characterization (t1/2) -Time Frame: Average of 2 years | — |
Countries
Australia, Belgium, Canada, France, Italy, Korea, Republic of, Poland, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactAssociate Director
Ascendis Pharma Oncology Division A/S
Outcome results
None listed