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CompletedLast updated: 25 January 2024

KEYNOTE-022: This phase I/II trial is evaluating the combination of an immunotherapy drug (Pembrolizumab) and two chemotherapy drugs (Dabrafenib and Trametinib) for the treatment of advanced MelanomaA Phase I/II Study to Assess the Safety and Efficacy of MK-3475 in Combination With Trametinib and Dabrafenib in Subjects With Advanced Melanoma

Clinical summary

Summary

This is a 5-part dose-finding and preliminary efficacy study of pembrolizumab (Pembro) + dabrafenib (D) + trametinib (T) for participants with advanced melanoma. Parts 1 and 2 are open-label to find and confirm the maximum tolerated dose (MTD)/maximum administered dose (MAD) for Pembro+D+T. The primary hypothesis (Parts 1 and 2) is that Pembro+D+T is sufficiently well-tolerated to permit clinical investigation. Part 3 is a double-blind study of Pembro+D+T versus placebo+D+T. The primary study hypothesis (Part 3 only) is that the Pembro+D+T improves progression-free survival (PFS) compared with placebo+D+T. Part 4 is nonrandomized and open-label and is designed to evaluate the safety and tolerability and identify the MTD or MAD of Pembro+T in participants who have v-raf murine sarcoma viral oncogene homolog B1 [BRAF] mutation-negative (without V600 E or K) melanoma or solid tumors [irrespective of BRAF status]. The primary hypothesis (Part 4) is that Pembro+T is sufficiently well-tolerated to permit clinical investigation. Part 5 will confirm the dose(s) identified in Part 4 in participants BRAF wild type [without V600E or K] melanoma or solid tumors [irrespective of BRAF status] and will further evaluate the safety and preliminary efficacy (Objective Response Rate [ORR]) of Pembro+T in participants who have BRAF wild type [without V600E or K] melanoma only. The primary hypotheses (Part 5) are that Pembro+T is sufficiently well-tolerated at the MTD/MAD to permit further clinical investigation and is effective in attaining objective responses based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator review in participants who have melanoma without BRAF V600 E or K mutations. Parts 1 and 2 of the study will also explore the MTD/MAD for open-label Pembro+T (for BRAF mutation-negative participants) concurrently with the Pembro+D+T arm; Pembro+D (for BRAF mutation-positive participants)

Conditions

This trial is treating patients with Melanoma.

Cancer

Skin Cancers Skin

Age

People18+

Phase

I/II

Trial Acronym

KEYNOTE-022

More information

Trial Identifiers

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Trial sponsor

Merck

Scientific Title

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

Eligibility

Inclusion

  • Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma excluding mucosal, or ocular melanoma (or a histologically or cytologically-documented locally-advanced or metastatic solid malignancy in Parts 4 and 5)
  • At least 1 measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI])
  • For solid tumors other than melanoma, (in Part 4 or 5 [dose confirmation only]), participants must 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 participants and treating physician. There is no limit to the number of prior treatment regimens, but prior treatment(s) should not include compounds targeting programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), BRAF, or mitogen-activated protein kinase (MEK). Treatment must end at least 4 weeks prior to randomization
  • BRAF mutation-positive (V600 E or K) melanoma for Parts 1, 2 and 3, or for Parts 1, 2, 4 and 5 only BRAF mutation-negative (wild type) melanoma with documented progression of ≥1 measurable lesion after prior therapy (if prior therapy was received). The inclusion criterion does not apply to participants with solid tumors in Parts 4 and 5 (dose confirmation only)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Anticipated life expectancy of at least 3 months
  • Able to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
  • Adequate organ function
  • Provide tissue for biomarker analysis from a newly or recently-obtained biopsy (within 90 days of Study Day 1) of a tumor lesion not previously irradiated
  • Female participants of non-childbearing potential must be willing to use highly effective contraceptive measures from the Screening Visit (Visit 1) through 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug
  • Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug

Exclusion

  • Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug
  • Prior systemic therapy (for participants who are BRAF mutation-positive), or BRAF mutation-negative and has received >1 prior systemic therapy for metastatic melanoma
  • Prior therapy with compounds targeting PD-1, PD-L1, BRAF, MEK or other molecules in the mitogen-activated protein kinase (MAPK) pathway
  • BRAF mutation-positive and has received prior systemic therapy with ipilimumab or other anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibodies. The BRAF exclusion criterion does not apply to participants with solid tumor in Parts 4 and 5 (dose confirmation only)
  • Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or not recovered from clinically significant adverse events due to cancer therapeutics administered more than 4 weeks prior to the first dose of study drug
  • Expected to require any other form of systemic or localized antineoplastic therapy while in this study
  • 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
  • Active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Active infection requiring systemic therapy
  • Active autoimmune disease, or documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
  • Previous severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
  • On chronic systemic steroid therapy (>10 mg/day prednisone or equivalent) within 2 weeks prior to first dose of study drug or on any other form of immunosuppressive medication
  • History or evidence of cardiovascular risk
  • Uncorrectable electrolyte abnormalities, long QT syndrome or taking medications known to prolong the QT interval
  • History of prior or current retinal vein occlusion (RVO)
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, their excipients, and/or dimethyl sulfoxide (DMSO)
  • Has had an allogeneic tissue/solid organ transplant, prior stem cell or bone marrow transplant
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Human immunodeficiency virus (HIV)
  • Hepatitis B or C
  • Received a live vaccine within 30 days prior to first dose of study drug
  • Pregnant or breastfeeding or expecting to conceive or father children from the Screening Visit (Visit 1) through 120 days after last dose of study drug

Inclusion

  • You are able to swallow medication by mouth.
  • Your cancer has spread to other parts of the body.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

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