A Phase I/II, multi-center, open label study of DYP688 in patients with MUM and other GNAQ/11 mutant melanomas (study CDYP688A12101)

Phase 2

Recruiting

Conditions: other melanoma
uveal melanoma
10030054

Registration Number: NL-OMON53721

Lead Sponsor: ovartis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 7

Inclusion Criteria

• Patients in the dose escalation part must be >=18 years of age at the time of
informed consent (ICF) signature. In the phase Il part, patients >=12 years of
age at the time of informed consent may be eligible for enrollment (for
Netherlands only >=18 years of age are eligible). Patients must have a minimum
weight of 40 kg.
• ECOG performance status <=1 for patients >=18 years of age; Karnofsky
performance status >=70
• Patients must be suitable and willing to undergo study required biopsies
according to the treating institution's own guidelines and requirements.
For all patients in Dose Escalation:
• 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.
• Non-MUM: advanced cutaneous or mucosal melanoma with histologically or
cytologically confirmed metastatic disease that has progressed following all
therapies or that has no satisfactory alternative therapies and has evidence of
GNAQ/11 mutation based on local data.
For patients in Phase Il:
• 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.
• 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.
• 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.

Exclusion Criteria

• Malignant disease, other than that being treated in this study.
• Active brain metastases, i.e. symptomatic brain metastases or known
leptomeningeal disease.
• 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.
• History of anaphylactic or other severe hypersensitivity / infusion reactions
to antibody-drug conjugate or monoclonal antibodies, which in the opinion of
the investigator may pose an increased risk of serious infusion reaction.
• Treatment with any of the following anti-cancer therapies prior to the first
dose of study treatment within the stated timeframes:
• <=2 weeks tor 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
nitrosourea compounds and mitomycin C.
• <=4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1
antagonists.
• Clinically significant and / or uncontrolled heart disease such as congestive
heart failure requiring treatment (NYHA grade >=2) or clinically significant
arrhythmia despite medical treatment.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase I:<br /><br>Safety : lncidence and severity of dose limiting toxicities during the first 28<br /><br>days of treatment. lncidence and severity of (serious) adverse events,<br /><br>including changes in laboratory values, ECGs, and vital signs.<br /><br>Tolerability: Frequency of dose interruptions, reductions, and discontinuations.<br /><br>Phase II:<br /><br>Overall Response rate (RECIST 1.1).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase I:<br /><br>PK parameters (e.g. AUG, Cmax, CL, half- life).<br /><br>Prevalence and incidence of anti-DYP688 antibodies.<br /><br>Best Overall Response, Overall Response Rate (RECIST v1.1).<br /><br>Phase II:<br /><br>Duration of response, progression free survival and Disease Control Rate<br /><br>(RECIST v1.1).<br /><br>Overall survival.<br /><br>Safety: lncidence and severity of (serious) adverse events, including changes<br /><br>in laboratory values, ECGs, and vital signs.<br /><br>Tolerability: Frequency of dose interruptions, reductions, and discontinuations.<br /><br>PK parameters (e.g., AUC, Cmax, CL, half- life).<br /><br>Assessment of immunogenicity of DYP688</p><br>