A Phase I/II Study to Assess the Safety and Efficacy of MK-3475 in Combination with Trametinib and Dabrafenib in Subjects with Advanced Melanoma - Phase I/II Study of MK-3475 in Combination with Trametinib and Dabrafenib

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.0 sites190 target enrollmentAugust 4, 2015

Conditionsadvanced or metastatic melanoma - all parts of the trialadvanced (unresectable and/or metastatic) solid tumours - Parts 4 and 5 MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864 MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864 Therapeutic area: Diseases [C] - Cancer [C04]

DrugsTafinlar Mekinist

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: advanced or metastatic melanoma - all parts of the trialadvanced (unresectable and/or metastatic) solid tumours - Parts 4 and 5
Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Enrollment: 190
Status: Active, not recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

August 4, 2015

End Date

TBD

Last Updated

4 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Eligibility Criteria

Inclusion Criteria

•The Subject must:
•1\.Have a histologically confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma or a histologically or cytologically\-documented locally\-advanced or metastatic solid malignancy,and have at least one measurable lesion as defined by RECIST 1\.1 on imaging studies (CT or MRI). Cutaneous lesions and other superficial lesions that are detectable only by physical examination and subcutaneous lesions detectable by CT are not considered measurable lesions for the purposes of this protocol, but may be considered as non\-target lesions.
•Mucosal or ocular melanoma are excluded.
•For solid tumors other than melanoma, the subject must be a participant in Part 4 or 5 (dose confirmation only), have a malignancy that is incurable and has either: (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds targeting PD\-1, PD\-L1, BRAF, or MEK. Treatment must end at least 4 weeks prior to randomization.
•2\.Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
•3\.Be \= 18 years of age on day of signing the informed consent.
•4\.Have BRAF mutation testing as determined at a local laboratory and either:
•a.Have a BRAF mutation\-positive (V600 E or K) tumor to be eligible for treatment with MK\-3475\+trametinib\+dabrafenib, trametinib\+dabrafenib or MK\-3475\+dabrafenib (if this part of the study is performed). If a subject’s initial specimen does not test BRAF mutation\-positive, a newly obtained specimen (different from the sample previously submitted) may be submitted for testing. If the newer specimen tests BRAF mutation\-positive, the subject meets this eligibility criterion.
•b.Have a BRAF mutation\-negative (wild type) tumor to be eligible for treatment with MK\-3475\+trametinib.
•Criterion 4a is applicable only to enrollment of melanoma subjects in Parts 1, 2, and 3 of the trial design. Criterion 4b is applicable only to enrollment of melanoma subjects in Parts 1, 2, 4, and 5 of the trial design. The inclusion criterion does not apply to solid tumor subjects in Parts 4 and 5 (dose confirmation only).

Exclusion Criteria

•1\. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
•2\. Is either:
•1\) BRAF mutation\-positive and has received prior systemic therapy for metastatic or advanced melanoma or
•2\) BRAF mutation\-negative and has received \>1 prior systemic therapy for metastatic melanoma. The BRAF exclusion criterion does not apply to solid tumour subjects in Parts 4 and 5 (dose confirmation only).
•3\. Has received prior therapy with compounds targeting the PD\-1, PD\-L1, BRAF, MEK or other molecules in the MAPK pathway.
•4\. Is BRAF mutation\-positive and has received prior systemic therapy with ipilimumab or other CTLA\-4 blocking antibodies.
•5\. Has had chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of trial treatment, or who has not recovered to CTCAE Grade 1 or better from the clinically significant AEs due to cancer therapeutics administered more than four weeks prior to the first dose of trial treatment.
•6\. Is expected to require any other form of systemic or localized antineoplastic therapy while in study.
•7\. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or stage 1\) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy. For dabrafenib\-containing treatment regimens in this study, subjects with any malignancy with confirmed activating RAS mutation are excluded.
•8\. Has known active central nervous metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are off systemic steroids for at least two weeks.