INCB039110 in Combination With Dabrafenib and Trametinib in Patients With BRAF-mutant Melanoma and Other Solid Tumors.

NCT03272464 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-380
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs as a possible treatment for BRAF-mutant melanoma. The drugs involved in this study are:

• Itacitinib (INCB039110)
• Dabrafenib
• Trametinib

Conditions

Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Maximum tolerated dose (MTD) is defined as the highest dose of the treatment that does not cause unacceptable side effects in at least two-thirds of participants.

  Approximately 2 months

Secondary Outcomes (3)

• Objective Response Rate

  Approximately 7 months

• Number of Participants With Progression-Free Survival at 6 Months

  6 Months

• Overall Survival

  approximately 7 months

Study Arms (1)

Trametinib + Dabrafenib + INCB039110

EXPERIMENTAL

* Dabrafenib is administered orally every 12 hours * Trametinib is administered orally once a day * INCB039110 is administered orally once a day

Drug: Trametinib; Drug: Dabrafenib; Drug: INCB039110

Interventions

Trametinib DRUG

Trametinib may work by binding to your cancer cells to inhibit the cancer cells' signals to decrease cell growth.

Also known as: Mekinist

Trametinib + Dabrafenib + INCB039110

Dabrafenib DRUG

Dabrafenib may work by stopping your cancer cells from duplicating.

Also known as: Tafinlar

Trametinib + Dabrafenib + INCB039110

INCB039110 DRUG

Itacitinib may work by stopping your tumor cells from living and growing.

Also known as: Itacitinib

Trametinib + Dabrafenib + INCB039110

Eligibility Criteria

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

You may qualify if:

• For Dose-Escalation Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below\*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy or not previously received BRAF targeted therapy, and for which standard curative or palliative measures do not exist or are no longer effective.
• If test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided to the Overall Principal Investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test).
• For Dose-Expansion Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below\*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy.
• If test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided to the Overall Principal Investigator (PI) for approval. (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test).
• Patients must have measurable disease by RECIST, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• Patients may have received any number of prior lines of therapy. All prior systemic anti-cancer treatment-related toxicities must be less than or equal to Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0; NCI, 2009) at the time of enrollment. This does not include alopecia and Grade 2 or less peripheral neuropathy.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of INCB039110 in combination with dabrafenib and trametinib in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
• Life expectancy of greater than 3 months in the opinion of the investigator.
• Patients must have acceptable organ and marrow function as defined below:
• Leukocytes (WBCs) ≥3,000/uL
• absolute neutrophil count ≥1,500/uL
• hemoglobin \> 9 g/dl (patients may be transfused to this level)
• platelets ≥ 100,000/uL
• total bilirubin \< 1.5 x institutional upper limit of normal OR \> 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range.

You may not qualify if:

• Patients who received prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiotherapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to Day 1 of Cycle 1. Patients are permitted to be on dabrafenib and trametinib at start of therapy without wash-out period prior to Day 1 of Cycle 1. Dosing will change to protocol determined dose levels on Day 1 of Cycle 1
• Patients must not have received prior JAK1 inhibitor therapy.
• Patients who are receiving any other investigational agents. Patients who have taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to registration.
• Patients with history of RAS mutation-positive tumors are not eligible regardless of interval from the current study. Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
• Patients must have no clinical evidence of leptomeningeal or brain metastasis causing spinal cord compression that are symptomatic, untreated, not stable for ≥ 4 weeks prior to Day 1 of Cycle 1 (must be documented by imaging), or requiring corticosteroids to manage metastasis-related symptoms. Subjects who have been off of corticosteroids for at least 2 weeks prior to Day 1 of Cycle 1 or are on a stable dose of ≤10 mg per day of a prednisone equivalent for \>1 month prior to Day 1 of Cycle 1 can be enrolled. Subjects must also be off of enzyme-inducing anticonvulsants for \>4 weeks prior to Day 1 of Cycle 1.
• History of known immediate or delayed hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to INCB039110, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because INCB039110, dabrafenib, and trametinib may have teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the mother being treated with the study drugs.
• History of interstitial lung disease or pneumonitis.
• Patients known to be HIV-positive patients and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• History of another malignancy other than the study indication under this trial within 5 years of study enrollment. Does not apply to subjects who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer, or other in situ cancers.
• History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):
• History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
• Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure \>21 mm Hg.
• History or evidence of cardiovascular risk including any of the following:

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Incyte Corporation: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

trametinib; dabrafenib; INCB039110; itacitinib

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

Results Point of Contact

• Title: David M. Miller, MD, PhD
• Organization: Massachusetts General Hospital

dmiller4@mgh.harvard.edu

617-726-2667

Study Officials

• David M. Miller, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: David M. Miller, MD, PhD

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: September 5, 2017
• Study Start: May 29, 2019
• Primary Completion: July 24, 2019
• Study Completion: December 27, 2019
• Last Updated: September 22, 2023
• Results First Posted: September 22, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)