E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MUM and other non-uveal, GNAQ/11 mutant melanomas |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Uveal Melanoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10081431 |
E.1.2 | Term | Uveal melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10030052 |
E.1.2 | Term | Ocular melanomas |
E.1.2 | System Organ Class | 100000004853 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. 2.ECOG performance status ≤ 1 for patients ≥ 18 years of age; Karnofsky performance status ≥ 70 for patients ≥ 16 and < 18 years of age; Lansky performance status ≥ 70 for patients ≥ 12 and < 16 years of age 3.Patients must be suitable and willing to undergo study required biopsies according to the treating institution’s own guidelines and requirements, if medically feasible. For all patients in Dose Escalation 4.MUM: uveal melanoma with histologically or cytologically confirmed metastatic disease. Patient must be either treatment naive or have received any number of prior lines and progressed on most recent therapy 5.Non-MUM: advanced cutaneous or mucosal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies and has evidence of GNAQ/11 mutation based on local data For patients in Phase II 6.Tebentafusp naïve group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies 7.Tebentafusp pre-treated group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease. Patients must be previously treated with tebentafusp and have progressed 8.Non-MUM: patients with diagnosis of cutaneous or mucosal melanomas harboring GNAQ/11 mutations based on local data, with histologically or cytologically confirmed metastatic disease that has progressed following all standard therapies or that has no satisfactory alternative therapies
Other protocol defined criteria may apply. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.: 28 days 2. and 3.: 9 months 4.: 17 months |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.: 26 months 2., 3. and 9.: 9 months 4. to 8.: 17 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
United States |
Switzerland |
France |
Germany |
Italy |
Netherlands |
Norway |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |