Pembrolizumab and Ibrutinib in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

NCT03021460 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC1577NCI-2017-0007916-002462
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose of ibrutinib when given together with pembrolizumab in treating patients with stage III-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ibrutinib may work better in treating patients with melanoma.

Conditions

Metastatic Melanoma; Stage III Cutaneous Melanoma AJCC v7; Unresectable Melanoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (Phase I)

  Will be defined as the highest dose level among those tested where at most one out of 6 patients develops a dose limiting toxicity prior to the start of their second course of treatment. The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

  Up to start of second course of treatment

• Tumor response (dose expansion cohort)

  Estimates of tumor response and binomial confidence intervals will be reported.

  Up to 5 years

Secondary Outcomes (3)

• Tumor response evaluated according to Response Evaluation Criteria in Solid criteria (RECIST)

  Up to 5 years

• Progression-free survival

  From study entry to the documentation of disease progression, assessed up to 5 years

• Overall survival

  From study entry to death due to any cause, assessed up to 5 years

Study Arms (1)

Treatment (ibrutinib, pembrolizumab)

EXPERIMENTAL

Patients receive ibrutinib PO daily on days 1-28 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles. Patients also receive pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of cycle 2 and subsequent cycles. Cycle 1 continues for 28 days and subsequent cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (ibrutinib, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy
• At least one non-nodal lesion considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (that is, a lesion whose longest diameter can be accurately measured as \>= 1.0 cm with computed tomography \[CT\] scan, CT component of a positron emission tomography \[PET\]/CT, or magnetic resonance imaging \[MRI\]) or at least one malignant lymph node is considered measurable by RECIST criteria (that is, its short axis is \>= 1.5 cm when assessed by CT scan)
• NOTE: tumor lesions in a previously irradiated area are not considered measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Provide informed written consent
• Patient is willing to undergo treatment and monitoring at the enrolling institution
• Willing to provide tissue and blood samples for correlative research purposes
• Histologic or cytologic confirmation of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy
• Only if patient has had previous exposure to anti-PD-1 or anti-PD-L1 therapy:
• Patient had disease progression on or within 6 months after anti-PD-1/anti-PD-L1 therapy in the metastatic setting OR
• Patient had disease progression within 6 months after the last dose of adjuvant/neoadjuvant anti-PD-1/anti-PD-L1 treatment
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)
• Platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to registration)
• Criteria must be met without a transfusion =\< four weeks prior to registration
• Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)

You may not qualify if:

• Any of the following:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study medication; adequate contraception is defined as 2 methods of birth control (e.g., hormonal contraceptives, intrauterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide) or prior surgical sterilization, or abstinence from heterosexual activity
• Prior treatment with ibrutinib or prior exposure to BTK inhibitors
• Uveal melanoma
• Current use of warfarin or other vitamin K antagonists
• Require continuous treatment with a strong CYP3A inhibitor
• Currently participating or has participated in a study of an investigational cancer therapy agent or using an investigational device within 28 days prior to study registration
• Live vaccines within 28 days prior to study pre-registration
• Invasive surgical procedure within 28 days prior to study pre-registration
• History of clinically severe (e.g., requires chronic immunosuppressive therapy, \[e.g., cyclosporine A, tacrolimus\]) autoimmune disease (e.g., ulcerative colitis, lupus), or history of organ transplant
• Known history of human immunodeficiency virus (HIV) infection, active infection with hepatitis B virus or hepatitis C virus, or any uncontrolled active systemic infection
• Gastrointestinal disease that might inhibit ibrutinib absorption (e.g., malabsorption syndrome, resection of the stomach or a large portion of small bowel, or partial/complete bowel obstruction), or unable to swallow capsules
• Active central nervous system metastases and/or carcinomatous meningitis

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Yao Y, Yan Y, Suman VJ, Dietz AB, Erskine CL, Dimou A, Markovic SN, McWilliams RR, Montane HN, Block MS. Phase I study of pembrolizumab in combination with ibrutinib for the treatment of unresectable or metastatic melanoma. Front Immunol. 2025 Feb 4;16:1491448. doi: 10.3389/fimmu.2025.1491448. eCollection 2025.

  PMID: 39967670 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Melanoma

Interventions

ibrutinib; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Matthew S. Block, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 16, 2017
• Study Start: January 31, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (1)