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Advanced Solid TumorPhase 2NCT04488003

Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations

A Phase 2 study testing Ulixertinib and Physician's Choice in people with Advanced Solid Tumor and BRAF Gene Mutation, run by BioMed Valley Discoveries, Inc at 22 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This BVD-523-ABC study builds on the safety and clinical activity experience of previous studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of patients with specific genetic alterations and tumor histologies that result in aberrant MAPK pathway signaling. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ulixertinib and Physician's Choice
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
22 sitesUnited States
Study dates
7 Jan 2021to 23 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with a locally advanced or metastatic malignancy, that has progressed following systemic therapy for their disease, if available, or for which the patient is not a candidate or refuses.
  • Tumors harboring a MEK or atypical BRAF alteration.
  • Provide signed and dated informed consent prior to initiation of any study-related procedures that are not considered standard of care (SoC).
  • Male or female patients aged ≥18 years.
  • Patients must have measurable disease by RECIST version 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
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  • Adequate renal function [creatinine ≤1.5 times ULN (upper limit of normal)] or a glomerular filtration rate (GFR) of ≥50 mL/min (using Cockcroft-Gault).
  • Adequate hepatic function [total bilirubin ≤1.5 times ULN; AST (aspartate transaminase) and ALT (alanine transaminase) ≤3 times ULN or ≤5 times ULN if the elevation is due to liver involvement by tumor].
  • Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x 109 cells/L; absolute neutrophil count ≥1.5 x 109 cells/L).
  • Adequate cardiac function: Left ventricular ejection fraction (LVEF) of >50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and a corrected QT interval (QTc) <480ms by the Fridericia method (QTcF).
  • Contraception - women: Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal (no menstrual cycle for at least 12 consecutive months), or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug. Abstinence is not considered an adequate contraceptive regimen.
  • Contraception - men: Must be surgically sterile, or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug.
  • Willing and able to participate in the trial and comply with all trial requirements.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agent may be included after consultation with the medical monitor.

Who cannot join

  • Gastrointestinal (GI) condition that could impair absorption of study medication (specific cases e.g., remote history of GI surgery, may be enrolled after discussion with the medical monitor) or inability to ingest study medication.
  • Uncontrolled or severe intercurrent medical condition.
  • Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change in the previous 4 weeks, can be allowed.
  • Having received any cancer-directed therapy (chemotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. Patients previously treated with radiotherapy must have recovered from the acute toxicities associated with such treatment.
  • Major surgery within 4 weeks prior to first dose.
  • Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 10 days between termination of the prior investigational drug and administration of study drug is required. In addition, any drug-related toxicity except alopecia should have recovered to Grade 1 or less.
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  • Prior therapy with any ERK inhibitor (e.g. LY3214996, LTT462).
  • Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g. encorafenib, dabrafenib, vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior BRAF and/or MEK inhibitor therapy is permitted for Groups 5 and 6.
  • For Part B, agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician's choice
  • Pregnant or breast-feeding women.
  • Any evidence of serious active infections. Patients are allowed to enroll if they have been fever-free for at least 48 hours and are on an active treatment that is not prohibited in Appendix 1 of the protocol.
  • Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study (based on the investigator's judgment).
  • A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
  • Concurrent therapy with any other investigational agent.
  • Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, and CYP3A4.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Duke University Medical Center / Duke Cancer Institute

    Durham, North Carolina, 27710

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • University of Florida

    Gainesville, Florida, 32610

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Kettering Cancer Center

    Kettering, Ohio, 45429

  • University of Wisconsin Clinical Science Center

    Madison, Wisconsin, 53792

  • Marshfield Medical Center

    Marshfield, Wisconsin, 54449

  • Tennessee Oncology, PLLC - Sarah Cannon (SCRI)

    Nashville, Tennessee, 37203

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Christiana Care Health Services / Helen F. Graham Cancer Center

    Newark, Delaware, 19713

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro-Minnesota Community Oncology Research Consortium (MMCORC)

    Saint Louis Park, Minnesota, 55416

  • University of Washington/Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Washington University School of Medicine - Siteman Cancer Center

    St Louis, Missouri, 63110

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Johns Hopkins Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

Official title: A Two-Part, Phase II, Multi-center Study of the ERK Inhibitor Ulixertinib (BVD-523) for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations

This BVD-523-ABC study builds on the safety and clinical activity experience of previous studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of patients with specific genetic alterations and tumor histologies that result in aberrant MAPK pathway signaling. Early clinical data have demonstrated anti-tumor activity with ulixertinib treatment and have identified specific groups of patients for whom additional development is warranted.

Read the detailed description

This multi-center, phase II study will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib (BVD-523) in patients with advanced malignancies.

Part A (tumor histology agnostic) will be open label and enroll patients to one of six groups based on their tumor alteration. Targeted enrollment per group was 38 patients with a total targeted enrollment of 228 patients. Actual enrollment was total of 104 patients with 77 patients allocated to treatment.

  • Group 1: Patients with tumors, other than colorectal cancer (CRC), having a BRAF alteration that results in an amino acid change at positions G469, L485, or L597.
  • Group 2: Patients with tumors, other than CRC, having a defined Class 2 BRAF alteration (see Appendix 2 of protocol).
  • Group 3: Patients with tumors, other than CRC, having an atypical BRAF alteration (non V600) that is not specified in Group 1 or Group 2.
  • Group 4: Patients with CRC having any atypical BRAF alteration.
  • Group 5: Patients with tumors, other than CRC, harboring alterations in MEK1/2.
  • Group 6: Patients with CRC harboring alterations in MEK1/2.

Part B (tumor histology specific) will randomly enroll patients with one of up to three specified tumor histologies to receive either ulixertinib or the physician's choice of treatment in a 2:1 ratio. Tumors must harbor a specified MEK or atypical BRAF alteration. If a patient progresses on physician's choice of treatment, crossover to the ulixertinib arm is permitted.The specific histologies to be included in this part will be selected based on available data and discussion with the clinical investigators, the medical monitor, and the sponsor. Total enrollment was targeted to approximately 80-100 patients per histology with up to three histologies included; however, the study was terminated prior to any patients enrolling in Part B.

Being tested
Ulixertinib, Physician's Choice
Keywords
atypical BRAF, non-V600

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UlixertinibDrug

    Also called BVD-523, BVD523

    Oral, 600 mg, twice daily, for 28-days in each treatment cycle

  • Physician's ChoiceDrug

    Physician's choice will be restricted to two approved (not off-label) treatments for each tumor histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician choice)).

Study groups in NCT04488003
Study groupRoleWhat they receive
Part A: UlixertinibExperimentalOral, 600 mg, twice daily, for 28-days in each treatment cycle
Receives: Drug: Ulixertinib
Part B: UlixertinibExperimentalOral, 600 mg, twice daily, for 28-days in each treatment cycle
Receives: Drug: Ulixertinib
Part B: Physician's choice of treatmentExperimentalPhysician's choice will be restricted to two approved (not off-label) treatments for each tumor histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician choice). If a patient progresses on physician's choice of treatment, crossover to the ulixertinib arm is permitted.
Receives: Drug: Physician's Choice

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Overall Response Rate (ORR) According to RECIST 1.1

    ORR will be defined as the percentage of patients achieving a Best Overall Response (BOR) of confirmed Complete Response (CR) and/or Partial Response (PR). Patients will be evaluated at baseline \& at periodic follow-up visits through the time their participation in the study is complete.The best responses will occur at different time points for each patient.

    Measured: Up to 25 months

Secondary outcomes (3)

  1. Part A: Progression Free Survival (PFS) According to RECIST 1.1

    PFS will be defined as time from first day of study drug to disease progression or death. Patients with no event will be censored at the last available tumor assessment. This analysis will be based on investigator assessment.

    Measured: 18 months

  2. Part A: Overall Survival (OS) According to RECIST 1.1

    OS will be defined as time from first day of study drug to death. Patients with no event will be censored at the last date the patient is known to be alive.

    Measured: 18 months

  3. Part A: Pharmacokinetic Concentration of BVD-523 at Steady State

    Single time point taken prior to taking study drug (trough) at steady state. Steady state is defined as patients who have received at least 5 days, or 10 consecutive doses, of study drug.

    Measured: Single time point drawn at Visit 4/approximately day 15 (or whenever the patient reaches steady state).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2020
  2. Study start7 Jan 2021
  3. Primary completion15 Feb 2023
  4. Study completion23 May 2023

Why it stopped: Enrollment challenges

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04488003
Sponsor's protocol ID
BVD-523-ABC
Status last verified
May 2024
First submitted
17 Jul 2020
Last updated
4 Jun 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22.

    PubMed 28939558

  • Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discov. 2018 Feb;8(2):184-195. doi: 10.1158/2159-8290.CD-17-1119. Epub 2017 Dec 15.

    PubMed 29247021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ulixertinib and Physician's Choice in people with Advanced Solid Tumor and BRAF Gene Mutation, run by BioMed Valley Discoveries, Inc at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Overall Response Rate (ORR) According to RECIST 1.1 (time frame: Up to 25 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04488003, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2024.

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