Immunotherapy with ipilimumab and nivolumab preceded or not by a targeted therapy with encorafenib and binimetinib

Phase 1

• Conditions: BRAF V600 mutation–positive unresectable or metastatic melanoma; MedDRA version: 20.0Level: SOCClassification code: 10029104Term: Neoplasms benign malignant and unspecified (incl cysts and polyps) Class: 2; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-505376-30-00
• Lead Sponsor: European Organisation For Research And Treatment Of Cancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-15
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

Histologically or cytologically confirmed unresectable stage III or IV cutaneous or mucosal melanoma (unknown primary also allowed), Adequate cardiac function: · left ventricular ejection fraction (LVEF) = 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram, · 12-lead ECG (in triplicate [2-5 minutes apart]). Single ECG should be obtained after the patient has been in a supine position for 5 minutes and recorded while the patient remains in that position on which QTcF must be <470 ms., Women of childbearing potential (WOCBP) must have a negative serum (preferred) or urine pregnancy test within 72 hours prior to registration. Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons., Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and after the study treatment: · for at least 5 months for a woman and 7 months for a man after the last study treatment (nivolumab and ipilimumab or nivolumab alone). · for a period of at least 2 months after last dose of encorafenib and binimetinib. Note: A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include: · Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) · Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) · Intrauterine device (IUD) · Intrauterine hormone-releasing system (IUS) · Bilateral tubal occlusion · Vasectomized partner · Sexual abstinence. Note: for patient that will receive encorafenib: there is a potential for encorafenib to induce CYP3A4, which may reduce the effectiveness of hormonal contraception methods. Therefore, the use of at least 1 form of non-hormonal contraception is required during participation in this study., Female patients must not be breast feeding during the trial treatment and for a period of at least 5 months after treatment discontinuation., Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up., Before patient registration/randomization and before any related study activity, written informed consent must be given according to ICH/GCP, and national/local regulations, Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrolment as per local assessment, Tumor tissue (FFPE) from an unresectable or metastatic site of disease must be provided for biomarker analyses. This can be an archived sample if obtained at maximum 3 months prior to randomization and if the patient did not receive treatment since then., Measurable disease per RECIST 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvis and brain CT/MRI performed within 28 days prior to randomization, Patients = 18

Exclusion Criteria

Uveal melanoma, Child-Pugh B/C and patients with history of acute or chronic pancreatitis, Known history or current evidence of active Hepatitis B (e.g., HBsAg reactive) or C (e.g., HCV RNA [qualitative] is detected), History of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies), Chronic use of immunosuppressive agents and/or systemic corticosteroids or any use in the last 2 weeks prior to the first dose of study treatment · Corticosteroid use as premedication for IV contrast allergies/reactions is allowed · Conditions requiring systemic treatment with <10 mg daily prednisone equivalents or equivalent doses of any other corticosteroid are allowed · History of interstitial lung disease (ILD) OR pneumonitis (other than chronic obstructive pulmonary disease (COPD) exacerbation) that has required oral or IV steroids are not allowed, Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed, Autoimmune paraneoplastic syndrome requiring immunosuppressive or dedicated treatment. A specific attention should be given in order to detect any minor myasthenia signs at enrolment; acetylcholine receptor antibodies will be systematically tested when symptoms are suggestive of a myastheni, History of any other hematologic or primary solid tumor malignancy, unless in remission for at least 5 years. A patient with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ or pT1a incidental prostate cancer, Previous allogeneic tissue/solid organ transplant, Active infection requiring therapy, Major surgery or trauma within 12 weeks prior to first dose of treatment or presence of any non-healing wound. Complete wound healing from major surgery must have occurred one month before the first dose of study treatment., Any symptomatic brain or leptomeningeal disease. Subjects with brain metastases are eligible if these have been locally treated and there is no magnetic resonance imaging (MRI) evidence of progression 4 weeks after end of treatment. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration., Minor surgery (including uncomplicated tooth extractions) within 28 days before randomization with complete wound healing at least 10 days before randomization is permitted., Any anticancer treatment within 4 weeks before randomization e.g., radiation, surgery, systemic therapy., Patients with clinically relevant ongoing complications from prior anticancer therapies., Severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); an ophthalmological assessment is mandatory within 28 days from the first dose of study treatment., History of retinal degenerative disease, Im

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified