A Phase II Study of Binimetinib in Combination With Imatinib in Patients With Advanced KIT-Mutant Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Binimetinib
- Conditions
- Melanoma Stage III
- Sponsor
- University of California, San Francisco
- Enrollment
- 25
- Locations
- 2
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This phase II trial studies how well binimetinib and imatinib work in treating patients with stage III-IV KIT-mutant melanoma that cannot be removed by surgery (unresectable). Binimetinib and imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and imatinib may help treat patients with KIT-mutant melanoma.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the overall response rate (ORR) of binimetinib plus imatinib in participants with advanced KIT-mutant melanoma. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of binimetinib plus imatinib in participants with advanced KIT-mutant melanoma. II. To estimate efficacy and survival parameters in participants with advanced KIT-mutant melanoma treated with binimetinib plus imatinib. III. To estimate efficacy in participants with advanced KIT-mutant melanoma treated with binimetinib plus imatinib. EXPLORATORY OBJECTIVES: I. To investigate association between changes in drug phosphorylated end products (p-KIT, p-MEK, p-ERK) and clinical response. II. To investigate association between clinical response and baseline Neurofibromatosis 1 (NF1) and SPRED1 status. III. To investigate pathologic correlates of acquired resistance. IV. To investigate whether NF1 and SPRED1 loss contribute to acquired resistance. V. To generate participant-derived xenograft models. VI. To determine the relationship between clinical outcomes and clinicopathologic features including KIT exon mutated, melanoma subtype, melanoma primary site, race/ethnicity, prior treatment history including immune checkpoint inhibitor (ICI)-experienced versus (vs) - naive. OUTLINE: Participants receive binimetinib orally (PO) twice daily (BID) on days 1-28 and imatinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at day 30 and 100, and then every 3 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- •Have histologically or cytologically confirmed melanoma
- •Have unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines, not amenable to local therapy
- •Have measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria
- •Have documentation of KIT-mutant melanoma by Clinical Laboratory Improvement Act (CLIA)-certified testing platform
- •Participants have progressed on prior standard-of-care therapy, or would be ineligible for or unable to tolerate standard-of-care therapy, in the opinion of the treating Investigator
- •For participants who have received prior ICI, the following is permitted:
- •Prior adjuvant or neoadjuvant ICI, if last dose administered at least 4 weeks prior to study drug start
- •Prior ICI for the treatment of unresectable/metastatic disease, if last dose administered at least 4 weeks prior to study drug start
- •Absolute neutrophil count \>= 1,500/microliter (mcL)
Exclusion Criteria
- •Has received systemic anti-cancer therapies within 3 weeks of study drug start, radiation within 2 weeks, antibody therapy within 4 weeks
- •Has not recovered from adverse events due to prior anti-cancer therapy to =\< grade 1 or baseline. Note: Stable chronic conditions (grade =\< 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll
- •Is currently receiving any other investigational agents or has received an investigational agent within 14 days or within 5 half-lives of investigational agent (whichever is shorter), prior to start of study drugs
- •Inability to swallow and retain study drugs
- •Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drugs (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, complete small bowel resection), or recent (=\< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs
- •Hypersensitivity to binimetinib or any of its excipients
- •Hypersensitivity to imatinib or any of its excipients
- •Concurrent neuromuscular disorder that is associated with elevated creatinine-kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
- •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity of hypercoagulability syndromes); history of retinal degenerative disease
- •Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
Arms & Interventions
Treatment (binimetinib, imatinib)
Patients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days
Intervention: Binimetinib
Treatment (binimetinib, imatinib)
Patients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days
Intervention: Imatinib
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: Up to week 16
Defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The ORR at stages 1 and 2 will be estimated using the method of Whitehead, and the p-values for testing the null hypothesis at each stage will use the method of Koyama \& Chen and 90% confidence interval will be reported.
Secondary Outcomes
- Progression-free survival (PFS)(Up to 2 years)
- Proportion of participants with treatment-related adverse events (AE)(Up to 2 years)
- Clinical benefit rate (CBR)(Up to 2 years)
- Median duration of response(Up to 2 years)
- Overall survival (OS)(Up to 2 years)