MUM and other non-uveal, GNAQ/11 mutant melanomas MedDRA version: 21.1 Level: PT Classification code 10081431 Term: Uveal melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10030052 Term: Ocular melanom
Conditions
Interventions
Product Name: DYP688
Product Code: DYP688
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Not established yet
Current Sponsor code: DYP688
Other descriptive name: DYP688
Con
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients in the dose escalation part must be = 18 years of age at the time of informed consent (ICF) signature. In the phase II part, patients = 12 years of age at the time of informed consent may be eligible for enrollment (not applicable in countries where enrollment is restricted by the local health authority to patients = 18 years of age). Patients must have a minimum weight of 40 kg. For the 32 mg/kg dose level a maximum weight limit of 115 kg may not be exceeded. 2.ECOG performance status = 1 for patients = 18 years of age; Karnofsky performance status = 70 for patients = 16 and =65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Malignant disease, other than that being treated in this study. 2.Active brain metastases, i.e. symptomatic brain metastases or known leptomeningeal disease. 3.Evidence of active bleeding or bleeding diathesis or significant coagulopathy (including familial) or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies. 4.History of anaphylactic or other severe hypersensitivity / infusion reactions to ADCs or monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction. 5.Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: •= 2 weeks for fluoropyrimidine therapy •= 4 weeks for radiation therapy or limited field radiation for palliation within = 2 weeks prior to the first dose of study treatment. •= 4 weeks or = 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent. •= 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C. •= 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists. 6.Clinically significant and / or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade = 2) or clinically significant arrhythmia despite medical treatment. Other protocol defined criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To characterize the safety and tolerability and to identify the MTD and/or RD and regimen for future studies of DYP688 as a single agent Phase II: To evaluate the anti-tumor activity of DYP688 as a single agent;Secondary Objective: Phase I •To characterize the pharmacokinetics (PK) of DYP688 as a single agent •To assess the immunogenicity (IG) of DYP688 as a single agent •To evaluate the preliminary anti-tumor activity of DYP688 as a single agent Phase II •To further evaluate the anti-tumor activity of DYP688 as a single agent •To evaluate the effects of DYP688 as a single agent on overall survival •To further characterize the safety and tolerability of DYP688 as a single agent •To further characterize the PK of DYP688 as a single agent •To further characterize the IG of DYP688 as a single agent ;Primary end point(s): 1. Phase I: Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment. 2. Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs 3. Phase I: Frequency of dose interruptions, reductions, and discontinuations 4. Phase II: Overall Response rate (ORR) per RECIST 1.1;Timepoint(s) of evaluation of this end point: 1.: 28 days 2. and 3.: 9 months 4.: 17 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Phase I and Phase II: PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life) 2. Phase I: Prevalence and incidence of anti-DYP688 antibodies 3. Phase I: Best Overall Response (BOR) 4. Phase I: Overall Response Rate (ORR) per RECIST v1.1 5. Phase II: Duration of response (DoR), progression free survival (PFS) and DCR per RECIST v1.1 6. Phase II: Overall survival (OS) 7. Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, electrocardiograms (ECGs), and vital signs 8. Phase II: Frequency of dose interruptions, reductions, and discontinuations PK parameters for total mAb, conjugated active and inactive payload, and unconjugated active payloads (e.g., AUC, Cmax, CL, half-life) 9. Phase II: Prevalence and incidence of anti-DYP688 antibodies;Timepoint(s) of evaluation of this end point: 1.: 26 months 2., 3. and 9.: 9 months 4. to 8.: 17 months | — |
Countries
Australia, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma Services AG
Outcome results
None listed