Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

NCT05441514 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 21751NCI-2022-04926P30CA033572
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety, side effects, and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving enasidenib and cobimetinib may kill more cancer cells in patients with relapsed or refractory acute myeloid leukemia.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity

  Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

  Cycle 1 (28 days)

• Incidence of adverse events

  Toxicity will be graded according to the NCI- CTCAE version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 30 days after last dose of study drug

Secondary Outcomes (7)

• Response

  Up to 1 year

• Minimal residual disease (MRD) status

  Up to 1 year

• Complete remission

  Up to 1 year

• Time to first response

  From first study does to first documented complete response, assessed up to 3 years

• Response duration

  From first study does to first documented complete response, assessed up to 1 year

Other Outcomes (3)

• Level of myeloid differentiation

  Up to 1 year

• Promotor methylation status of RAS pathway regulator

  Up to 1 year

• Changes in RAS pathway regulatory gene expression levels

  Pre and post- treatment, assessed up to 1 year

Study Arms (1)

Treatment (cobimetinib, enasidenib mesylate)

EXPERIMENTAL

Patients receive cobimetinib PO QD on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cobimetinib; Drug: Enasidenib Mesylate

Interventions

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Treatment (cobimetinib, enasidenib mesylate)

Enasidenib Mesylate DRUG

Given PO

Also known as: 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007, Enasidenib Methanesulfonate, Idhifa

Treatment (cobimetinib, enasidenib mesylate)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed AML, according to WHO criteria, with refractory/relapsed (R/R) disease who are ineligible for therapies known to be effective for treatment of their AML.
• Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow involvement
• Patients with acute promyelocytic leukemia (APL) will not be eligible
• Patients with IDH2 mutations, who were previously treated with enasidenib are allowed
• Have a documented IDH2 gene mutation (≥ 2% allele frequency) and a concomitant detectable RAS-pathway mutation (as determined by local testing), involving NRAS, KRAS, HRAS, BRAF, KIT, RIT1, PTPN11, CBL or NF1 genes.
• Adults aged ≥ 18 years
• ECOG ≤ 2
• WBC ≤25 x 10\^9/L prior to initiation of enasidenib.

You may not qualify if:

• Current or planned use of other investigational agents, antineoplastic, chemotherapy, radiation therapy, biological therapy, immunotherapy or major surgery within 2 weeks or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy (exception: hydroxyurea is allowed in cycles 1 and 2 for control of rapidly progressing leukemia or for treatment of enasidenib-related leukocytosis)
• Systemic steroid therapy \> 10 mg/day (≤ 10mg/day prednisone equivalent ok) or any other form of immunosuppressive medication within 28 days, except as required for treatment of differentiation syndrome
• Strong and moderate CYP3A4 inducers/inhibitors (moderate CYP3A4 inhibitors only allowed on Principal Investigator approval) within 14 days or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy
• Foods/supplements that are strong or moderate inhibitors or inducers of CYP3A (such as grapefruit, Seville oranges, starfruit and St. John's wort) within 7 days prior to initiation of and during study treatment
• Gastrointestinal disorder such as maladsorption syndrome or any other disorder that may interfere with oral drug absorption
• Clinically significant cardiac morbidities (Class III/IV cardiovascular disability according to the New York Heart Association Classification, arrhythmia not stable on medical management, acute cardiovascular ischemic event within 6 months of enrollment, etc)
• Active CNS disease

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

cobimetinib; 2-Propanol; methanesulfonic acid; enasidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Propanols; Alcohols; Organic Chemicals

Study Officials

• Brian Ball

  City of Hope Medical Center

  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: June 28, 2022
• First Posted: July 1, 2022
• Study Start: April 28, 2023
• Primary Completion: March 19, 2026
• Study Completion: March 19, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (1)