NCT05221320

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

Terminated Phase 2 Results posted Last updated 25 September 2025

What this trial tests

Phase 2 trial testing Ulixertinib in Tumor, Solid in 47 participants. Terminated before completion.

Timeline

26 May 2022

Primary endpoint
8 May 2024

14 July 2024

Quick facts

Lead sponsor	BioMed Valley Discoveries, Inc
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	26 May 2022
Primary completion	8 May 2024
Estimated completion	14 July 2024
Sites	9 locations across United States

Drugs / interventions tested

• Ulixertinib (ulixertinib) — full drug profile →
• Hydroxychloroquine (HYDROXYCHLOROQUINE) — full drug profile →

Conditions studied

• Tumor, Solid — all drugs for Tumor, Solid →
• Gastrointestinal Cancer — all drugs for Gastrointestinal Cancer →

Sponsor

BioMed Valley Discoveries, Inc — full company profile →

Who can join

18 and older, any sex, with Tumor, Solid or Gastrointestinal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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.

Group	Value	95% CI
Basket 1: Cholangiocarcinoma Including Intrahepatic, Perihilar, Extrahepatic Cholangiocarcinoma	0
Basket 2 - Pancreatic Adenocarcinoma	0
Basket 3 - Colorectal Adenocarcinoma	0
Basket 4 - Esophageal Adenocarcinoma, Esophageal Squamous, Gastroesophageal Junction	0
Basket 5 - Gastric Adenocarcinoma	0
Stage 2 - Basket Expansion Based on Stage 1	0

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

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

Group	Value	95% CI
Basket 1: Cholangiocarcinoma Including Intrahepatic, Perihilar, Extrahepatic Cholangiocarcinoma	3
Basket 2 - Pancreatic Adenocarcinoma	10
Basket 3 - Colorectal Adenocarcinoma	12
Basket 4 - Esophageal Adenocarcinoma, Esophageal Squamous Cell, Gastroesophageal Junction	0
Basket 5 - Gastric Adenocarcinoma	1

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

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

Group	Value	95% CI
Basket 1: Cholangiocarcinoma Including Intrahepatic, Perihilar, Extrahepatic Cholangiocarcinoma	4
Basket 2 - Pancreatic Adenocarcinoma	18
Basket 3 - Colorectal Adenocarcinoma	22
Basket 4 - Esophageal Adenocarcinoma, Esophageal Squamous Cell, Gastroesophageal Junction	2
Basket 5 - Gastric Adenocarcinoma	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. Secondary · 18 months

To assess the duration of efficacy of ulixertinib and hydroxychloroquine in patients with advanced, RAS, non-V600 BRAF, ERK, or MEK mutated gastrointestinal malignancies.

Group	Value	95% CI
Stage 1 - Cholangiocarcinoma	5.5	0.7 – 5.5
Stage 1 - Pancreas	1.9	1.7 – 2.1
Stage 1 - Colorectal	1.8	1.4 – 1.8
Stage 1 - Esophageal	2.8	1.7 – 3.9
Stage 1 - Gastric	0.7	0.7 – 0.7

Adverse events — posted to ClinicalTrials.gov

Time frame: All reportable events were recorded with start dates occurring any time after informed consent obtained through and including 30 calendar days after the last administration of ulixertinib and hydroxychloroquine. The median (min; max) number of cycles received was 2 (1; 6). The median (min; max) duration of exposure was 1.74 (0.0; 5.5) months. All patients fell well within the estimated 24 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Stage 1 - Cholangiocarcinoma

Serious: 3/4 (75%)

Deaths: 1/4

Stage 1 - Pancreas

Serious: 10/18 (56%)

Deaths: 12/18

Stage 1 - Colorectal

Serious: 12/22 (55%)

Deaths: 15/22

Stage 1 - Esophageal

Serious: 0/2 (0%)

Deaths: 2/2

Stage 1 - Gastric

Serious: 1/1 (100%)

Deaths: 1/1

Stage 2 - Basket Expansion Based on Stage 1

Serious: 0

Deaths: 0

Serious adverse events (26 terms)

Reaction	System	Stage 1 - Cholangiocarcinoma	Stage 1 - Pancreas	Stage 1 - Colorectal	Stage 1 - Esophageal	Stage 1 - Gastric	Stage 2 - Basket Expansion…
Disease progression	General disorders	—	—	—	—	—	—
Obstruction gastric	Gastrointestinal disorders	—	—	—	—	—	—
Electrocardiogram QT prolonged	Investigations	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Oesophageal varices haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Biliary obstruction	Blood and lymphatic system disorders	—	—	—	—	—	—
Cholangitis	Hepatobiliary disorders	—	—	—	—	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Spontaneous bacterial peritonitis	Infections and infestations	—	—	—	—	—	—
Peritonitis bacterial	Infections and infestations	—	—	—	—	—	—
Failure to thrive	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Metabolic encephalopathy	Nervous system disorders	—	—	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—	—	—
Device occlusion	Product Issues	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—

Other adverse events (52 terms — click to expand)

Reaction	System	Stage 1 - Cholangiocarcinoma	Stage 1 - Pancreas	Stage 1 - Colorectal	Stage 1 - Esophageal	Stage 1 - Gastric	Stage 2 - Basket Expansion…
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Disease Progression	General disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Dyspepsis	Gastrointestinal disorders	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—	—	—	—	—
Electrocardiogram QT prolonged	Investigations	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypocalcaemia	Investigations	—	—	—	—	—	—
Hypophosphataemia	Investigations	—	—	—	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—
Protein total decreased	Investigations	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—

Most-reported serious reactions: Disease progression, Obstruction gastric, Electrocardiogram QT prolonged, Anaemia, Abdominal pain, Lower gastrointestinal haemorrhage, Oesophageal varices haemorrhage, Vomiting.

Data from ClinicalTrials.gov NCT05221320 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.
   Yin G, Huang J, Petela J, Jiang H, et al · · 2023 · cited 50× · PMID 37221195 · DOI 10.1038/s41392-023-01441-4
2. Natural products targeting the MAPK-signaling pathway in cancer: overview.
   Shi A, Liu L, Li S, Qi B. · · 2024 · cited 40× · PMID 38193944 · DOI 10.1007/s00432-023-05572-7
3. Enhancing Anti-Cancer Therapy with Selective Autophagy Inhibitors by Targeting Protective Autophagy.
   Lee MJ, Park JS, Jo SB, Joe YA. · · 2023 · cited 28× · PMID 36579459 · DOI 10.4062/biomolther.2022.153
4. The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.
   Shan C, Wang Y, Wang Y. · · 2024 · cited 27× · PMID 39664581 · DOI 10.7150/ijbs.103187
5. Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.
   Hassan AMIA, Zhao Y, Chen X, He C. · · 2024 · cited 26× · PMID 39000565 · DOI 10.3390/ijms25137459
6. Inhibition of autophagy; an opportunity for the treatment of cancer resistance.
   Tonkin-Reeves A, Giuliani CM, Price JT. · · 2023 · cited 15× · PMID 37363731 · DOI 10.3389/fcell.2023.1177440
7. KRAS inhibition in metastatic colorectal cancer: An update.
   Nusrat M, Yaeger R. · · 2023 · cited 14× · PMID 36638742 · DOI 10.1016/j.coph.2022.102343
8. Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review.
   Zhang Y, Song J, Zhang Y, Li T, et al · · 2022 · cited 12× · PMID 36613779 · DOI 10.3390/ijms24010334