Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies

NCT05221320 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: BVD-523-HCQ
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 9

Brief Summary

This is an open-label, prospective phase two basket trial assessing the efficacy of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies. All patients enrolled must have a mitogen-activated protein kinase (MAPK) activating mutation to be deemed eligible for trial participation. Each disease-based basket will open to enrollment in two-stages. The opening of stage two will be dependent on the observed responses in the patients enrolled in the first stage.

Conditions

Tumor, Solid; Gastrointestinal Cancer

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate as Defined by the Proportion of Patients Achieving a Confirmed Partial Response (PR) and Complete Response (CR) (Defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Evaluated by the Local Treating Investigator.

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.

  from cycle 1 day 1 until safety follow-up visit (up to 24 months)

• The Incidence and Frequency of Serious Adverse Events (SAEs) Characterized by Type, Severity (as Defined by the NCI CTCAE, Version 5.0), Seriousness, Duration, and Relationship to Study Treatment.

  Reporting of any SAEs, all SAEs were collected/assessed at each study visit.

  Baseline until safety follow-up visit (up to 24 months)

• The Incidence and Frequency of Adverse Events (AEs), Characterized by Type, Severity (as Defined by the NCI CTCAE, Version 5.0), Seriousness, Duration, and Relationship to Study Treatment.

  Reporting of any AEs, all AEs were collected/assessed at each study visit.

  Baseline until safety follow-up visit (up to 24 months)

Secondary Outcomes (1)

• Progression-free Survival (PFS) as Defined as the Time From Study Drug Initiation to the Time of Documented Disease Progression (as Assessed by RECIST 1.1) or Death From Any Cause.

  18 months

Study Arms (2)

Stage 1 - 5 baskets included, based on primary disease

EXPERIMENTAL

Ulixertinib: 450mg twice daily (BID), orally, days 1-28 Hydroxychloroquine: 600mg BID, orally, days 1-28 Cycles repeat every 28 days in absence of disease progression or unacceptable toxicity

Drug: Ulixertinib; Drug: Hydroxychloroquine

Stage 2 - basket expansion based on Stage 1

EXPERIMENTAL

Ulixertinib: 450mg BID, orally, days 1-28 Hydroxychloroquine: 600mg BID, orally, days 1-28 Cycles repeat every 28 days in absence of disease progression or unacceptable toxicity

Drug: Ulixertinib; Drug: Hydroxychloroquine

Interventions

Ulixertinib DRUG

small molecule ERK 1/2 inhibitor

Also known as: BVD-523, BVD523

Stage 1 - 5 baskets included, based on primary disease; Stage 2 - basket expansion based on Stage 1

Hydroxychloroquine DRUG

Autophagy inhibitor

Stage 1 - 5 baskets included, based on primary disease; Stage 2 - basket expansion based on Stage 1

Eligibility Criteria

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

You may qualify if:

• Male or female patient aged ≥ 18 years.
• Histologically confirmed esophageal adenocarcinoma, esophageal squamous cell carcinoma, GEJ adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, extrahepatic cholangiocarcinoma, or colorectal adenocarcinoma harboring a MAPK-mutated GI malignancy: KRAS, NRAS, HRAS, BRAF non-V600, MEK 1/2 (MAP2K1/2), or ERK 1/2 (MAPK3/1).
• Progression on or during standard lines of therapy:
• Patients with intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, or extrahepatic cholangiocarcinoma must have progressed during or after receiving a first-line regimen of gemcitabine/cisplatin unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
• Patients with pancreatic adenocarcinoma must have progressed during or after first-line therapy of FOLFIRINOX/ mFOLFIRINOX, gemcitabine/nab-paclitaxel unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
• Patients with colorectal adenocarcinoma must have progressed during or after their first two lines of therapy, including FOLFOX ± Avastin and FOLFIRI ± Avastin, unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
• Patients with esophageal adenocarcinoma, esophageal squamous cell carcinoma, GEJ adenocarcinoma, or gastric adenocarcinoma must have progressed during or after their first two lines of therapy.
• Acceptable first-line regimens: FOLFOX, 5-FU/Cisplatin, FOLFIRI, Paclitaxel/Cisplatin or Carboplatin, Docetaxel/Cisplatin, DCF (or modifications thereof), or ECF (or modifications thereof) unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
• Acceptable second-line regimens: Ramucirumab/Paclitaxel, Docetaxel, Paclitaxel, Irinotecan, Trifluridine/Tipiracil, or FOLFIRI, unless deemed ineligible by the treating investigator to receive chemotherapy-based regimens due to prior comorbidities.
• Patients with deficient MisMatch Repair/High levels of MicroSatellite Instability (dMMR/MSI-H) tumors must have progressed during or after pembrolizumab.
• Measurable disease by RECIST 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI).
• Willing to provide a biopsy at the time points indicated on the Schedule of Activities.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Adequate organ function as defined as:
• Hematologic:

You may not qualify if:

• Received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter.
• Received radiotherapy ≤ 14 days prior to the first dose of study treatment.
• Note: Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe.
• Undergone major surgery ≤ 3 weeks prior to starting study drug or who have not fully recovered from major surgery.
• The diagnosis of another malignancy within ≤ 3 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6).
• Known uncontrolled brain metastases or cranial epidural disease.
• Note: Patients with stable brain metastases either treated or being treated with a stable dose of steroids (\<20 mg of prednisone daily or equivalent) or anticonvulsants, with no dose change within 4 weeks before the first study drug dose, and no anticipated dose change, are eligible. In the event of steroid taper post-radiation therapy, taper must be complete within 2 weeks before Baseline.
• History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity).
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
• Duration of QT interval (QTc prolongation) defined as a QTcF \> 500 ms.
• Known congenital long QT.
• Left ventricular ejection fraction \< 50%.

Sponsors & Collaborators

• BioMed Valley Discoveries, Inc: lead

Study Sites (9)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Rogel Cancer Center, University of Michigan Health

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Massey Cancer Center, Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Neoplasms; Gastrointestinal Neoplasms

Interventions

ulixertinib; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Baskets 2 and 3 did not proceed past stage 1 due to futility. No definite conclusions can be drawn from baskets 1, 4 and 5 due to slow enrollment and early closure of the study. Early termination leading to small numbers of patients analyzed.

Results Point of Contact

• Title: Deborah Knoerzer, Director Translational Sciences
• Organization: Biomed Valley Discoveries

dknoerzer@biomed-valley.com

6368876429

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: February 2, 2022
• Study Start: May 26, 2022
• Primary Completion: May 8, 2024
• Study Completion: July 14, 2024
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)