Metastatic Colorectal AdenocarcinomaPhase 1NCT06696768

Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer

A Phase 1 study testing Bevacizumab, Biopsy Procedure and Biospecimen Collection in people with Metastatic Colorectal Adenocarcinoma and Stage III Colorectal Cancer AJCC v8, run by National Cancer Institute (NCI) at 13 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Colorectal Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8
What is being tested?: Bevacizumab, Biopsy Procedure and Biospecimen Collection
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 13 sitesUnited States
Study dates: 23 Jun 2025to 31 Dec 2026
Phase: Phase 1
Are there results?: Not yet: the study is under way

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 must have histologically or cytologically confirmed colorectal adenocarcinoma
Patients must have unresectable or metastatic measurable disease on imaging for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determination within 28 days of registration
For patients enrolling to the expansion cohort, lesions must be amenable to research biopsy
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CA-4948 (emavusertib) and FOLFOX in combination with bevacizumab in patients < 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)
Absolute neutrophil count ≥ 1,500/mcL (within 28 days of registration)

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Platelets ≥ 75,000/mcL (within 28 days of registration)
Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (within 28 days of registration)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × institutional ULN; for those with liver metastases, 5 × institutional ULN (within 28 days of registration)
Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m^2 (within 28 days of registration)
Creatine phosphokinase (CPK) elevation at screening < grade 2 (CPK ≤ 2.5 x ULN) (within 28 days of registration)
Patients on a cholesterol lowering statin must be on a stable dose with no dose changes within 3 weeks prior to study start
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible, after discussion with the principal investigator (PI) or National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Investigational Drug Branch (IDB) Monitor, if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of therapy
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 regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
Patients must be able to take oral medications
The effects of CA-4948 (emavusertib) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of childbearing potential must continue contraception for 9 months following the last dose of study drugs. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol and involved with women of childbearing potential must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months following the last dose of study drugs
Patients must have the ability to understand and the willingness to sign a written informed consent document

Who cannot join

Patients with high-frequency microsatellite instability (MSI-H) or deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) colorectal cancer at pre-enrollment screening
Patients with prolonged QT interval by Fridericia's correction formula (QTcF) (> 450ms) on screening electrocardiogram (ECG)
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia
Patients who are receiving any other investigational agents
Patients who have received prior treatment with any chemotherapy (either in the adjuvant or metastatic setting), including FOLFOX, fluorouracil/leucovorin/irinotecan (FOLFIRI), folinic acid/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI), or antiangiogenic agents such as bevacizumab and similar agents, are not eligible for this study
Patients with a known dihydropyrimidine dehydrogenase deficiency

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Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 (emavusertib) or other agents used in the study
Patients with a gastrointestinal (GI) condition that could impair absorption of CA-4948 (emavusertib) or cause an inability to ingest CA-4948 (emavusertib)
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant women are excluded from this study because CA-4948 (emavusertib) is a blood-brain barrier penetrant with the potential for 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 CA-4948 (emavusertib), breastfeeding should be discontinued if the mother is treated with CA-4948 (emavusertib). These potential risks may also apply to other agents used in this study. Women of childbearing potential must have a negative pregnancy test within 7 days of study registration
Patients with a history of allogeneic organ or stem cell transplantation
Patients with significant active bleeding or those in whom the treating physician believes bevacizumab would not be safe or appropriate
Patients who have had palliative radiation to bone metastases within 2 weeks prior to day 1 of the study treatment
Patients who have had a major surgical procedure within 4 weeks prior to day 1 of the study treatment
Patients with hypertension not controlled by antihypertensive medication
Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to treatment; however,
Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of ≤ 10 mg/day methylprednisolone equivalent) may be enrolled
The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
Severe infections within 28 days prior to treatment, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. This includes receipt of oral or IV antibiotics within 14 days prior to registration. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

City, postcode or hospital

Sites recruiting now only

13 sites in 1 country

United States13 sites, 13 recruiting

Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Moh'd Khushman
Recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Moh'd Khushman
Recruiting
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Raed Al-Rajabi
Recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Site Public Contact, 352-273-8010, cancer-center@ufl.edu
Thomas J. George
Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Raed Al-Rajabi
Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Kristen K. Ciombor
Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Susanna V. Ulahannan
Recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Raed Al-Rajabi
Recruiting
Memorial Hospital East
Shiloh, Illinois, 62269
Site Public Contact, 314-747-9912, dschwab@wustl.edu
Moh'd Khushman
Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Moh'd Khushman
Recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Moh'd Khushman
Recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Site Public Contact, 800-600-3606, info@siteman.wustl.edu
Moh'd Khushman
Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Raed Al-Rajabi
Recruiting

Other trials in United States

About this study

Official title: Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer

This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLFOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

To assess dose-limiting toxicities (DLTs) and determine the recommended phase 2 dose (RP2D) of CA-4948 (emavusertib) in combination with leucovorin (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab in first-line treatment for patients with advanced or metastatic non-operable colorectal cancer (mCRC).

II. To evaluate the safety and tolerability of the combination of CA-4948 (emavusertib) and FOLFOX plus bevacizumab.

SECONDARY OBJECTIVES:

To observe and record anti-tumor activity. II. To evaluate ribonucleic acid sequencing (RNAseq) data to examine the impact of interleukin 1 receptor associated kinase 4 (IRAK4) inhibition on downstream signaling in tumor samples.

EXPLORATORY OBJECTIVES:

To evaluate pharmacodynamic (PD) effect of CA-4948 (emavusertib) in combination with chemotherapy.

II. To evaluate pharmacokinetics (PKs) of CA-4948 (emavusertib) in combination with chemotherapy.

III. To explore biomarkers and genomic alterations associated with treatment response.

IV. To evaluate if certain gene mutations alone or in combination are associated with response, progression free survival (PFS), and/or overall survival (OS).

OUTLINE: This is a dose-escalation study of CA-4948 in combination with FOLFOX plus bevacizumab followed by a dose-expansion study. Patients are assigned to 1 of 2 groups.

GROUP A: Patients receive CA-4948 orally (PO) twice daily (BID) on days 1-14 of each cycle, bevacizumab intravenously (IV) over 30-90 minutes on day 1 of each cycle beginning in cycle 1, and oxaliplatin IV over 120 minutes, leucovorin calcium (leucovorin) IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT throughout the trial. Patients may also undergo tumor biopsy throughout the trial.

GROUP B: Patients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 2, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients also undergo tumor biopsy throughout the trial.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months after end of treatment.

Conditions: Metastatic Colorectal Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Adenocarcinoma
Being tested: Bevacizumab, Biopsy Procedure, Biospecimen Collection, Computed Tomography, Emavusertib
Medical subject headings: Colorectal Neoplasms

What participants receive

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

BevacizumabBiological
Also called ABP 215, ABP-215, ABP215, Alymsys
Given IV
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT or PET/CT
EmavusertibBiological
Also called AU 4948, AU-4948, CA 4948, CA-4948
Given PO
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Given IV
Leucovorin CalciumDrug
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
OxaliplatinDrug
Also called 1-OHP, Ai Heng, Aiheng, Dacotin
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT

Study groups in NCT06696768
Study group	Role	What they receive
Group A (CA-4948, bevacizumab, FOLFOX)	Experimental	Patients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 1, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients may also undergo tumor biopsy throughout the trial. Receives: Biological: Bevacizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Emavusertib; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography
Group B (CA-4948, bevacizumab, FOLFOX)	Experimental	Patients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 2, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients also undergo tumor biopsy throughout the trial. Receives: Biological: Bevacizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Emavusertib; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography

What is being measured

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

Dose limiting toxicities (DLT)
DLT will be based on the first 2 cycles (28 days) of emavusertib.
Measured: Up to 2 cycles (Cycle length = 14 days)
Incidence of treatment-emergent adverse events
The adverse events will be recorded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Measured: Up to 2 cycles (Cycle length = 14 days)

Secondary outcomes (6)

Incidence of adverse events
Adverse events, graded according to the National Cancer Institute CTCAE v5 for each cohort, will be analyzed using descriptive statistics.
Measured: Baseline to 30 days after last dose of study drug
Overall response rate
Defined as the percentage of patients who achieve complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
Measured: From the start of treatment until disease progression/recurrence, assessed up to 12 months after end of treatment
Progression free survival
Will be assessed using RECIST v1.1.
Measured: From first dose to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 12 months after end of treatment
Overall survival
Measured: From the date of first dose to the date of death by any cause, assessed up to 12 months after end of treatment
Disease control rate
Defined as the percentage of patients who achieve a best response of CR, PR, or stable disease (SD) per RECIST v1.1 at any time during their treatment. A determination of SD requires that the first restaging imaging scan be performed after 4 cycles of treatment (8 weeks from start of treatment +/- 7 days).
Measured: Up to 12 months after end of treatment
Molecular profiling
Molecular profiling by next generation sequencing will be done to assess the impact of IRAK4 inhibition on downstream signaling in tumor samples.
Measured: At baseline, between cycle (C) 1 day (D) 10 and C1D14, and disease progression

Timeline

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

23 Jun 202531 Dec 2026

First posted20 Nov 2024
Study start23 Jun 2025
Primary completion31 Dec 2026 (estimated)
Study completion31 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Metastatic Colorectal AdenocarcinomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 24 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06696768
Sponsor's protocol ID: NCI-2024-09416
Other IDs: NCI-2024-09416, 10655, 10655, UM1CA186689
Status last verified: Sep 2026
First submitted: 19 Nov 2024
Last updated: 9 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
RecruitingPhase 1
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Advanced Breast Cancer, Metastatic Breast Cancer (HR+/ HER2-)

All Metastatic Colorectal Adenocarcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT06696768
Acronym / sponsor ID: NCI-2024-09416
Conditions: Metastatic Colorectal Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Adenocarcinoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 24 participants (estimated)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 23 Jun 2025 (actual)
Primary completion: 31 Dec 2026 (estimated)
Study completion: 31 Dec 2026 (estimated)
First posted: 20 Nov 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To assess dose-limiting toxicities (DLTs) and determine the recommended phase 2 dose (RP2D) of CA-4948 (emavusertib) in combination with leucovorin (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab in first-line treatment for patients with advanced or metastatic non-operable colorectal cancer (mCRC).

II. To evaluate the safety and tolerability of the combination of CA-4948 (emavusertib) and FOLFOX plus bevacizumab.

SECONDARY OBJECTIVES:

To observe and record anti-tumor activity. II. To evaluate ribonucleic acid sequencing (RNAseq) data to examine the impact of interleukin 1 receptor associated kinase 4 (IRAK4) inhibition on downstream signaling in tumor samples.

EXPLORATORY OBJECTIVES:

To evaluate pharmacodynamic (PD) effect of CA-4948 (emavusertib) in combination with chemotherapy.

II. To evaluate pharmacokinetics (PKs) of CA-4948 (emavusertib) in combination with chemotherapy.

III. To explore biomarkers and genomic alterations associated with treatment response.

IV. To evaluate if certain gene mutations alone or in combination are associated with response, progression free survival (PFS), and/or overall survival (OS).

OUTLINE: This is a dose-escalation study of CA-4948 in combination with FOLFOX plus bevacizumab followed by a dose-expansion study. Patients are assigned to 1 of 2 groups.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months after end of treatment.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Group A (CA-4948, bevacizumab, FOLFOX)	Experimental	Biological: Bevacizumab, Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Emavusertib, Drug: Fluorouracil, Drug: Leucovorin Calcium, Procedure: Magnetic Resonance Imaging, Drug: Oxaliplatin, Procedure: Positron Emission TomographyPatients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 1, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients may also undergo tumor biopsy throughout the trial.
Group B (CA-4948, bevacizumab, FOLFOX)	Experimental	Biological: Bevacizumab, Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Emavusertib, Drug: Fluorouracil, Drug: Leucovorin Calcium, Procedure: Magnetic Resonance Imaging, Drug: Oxaliplatin, Procedure: Positron Emission TomographyPatients receive CA-4948 PO BID on days 1-14 of each cycle, bevacizumab IV over 30-90 minutes on day 1 of each cycle beginning in cycle 2, and oxaliplatin IV over 120 minutes, leucovorin IV over 2 hours, and fluorouracil IV bolus (optional) followed by continuous IV infusion over 46 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After treatment for 2 years, patients may continue treatment after discussion with the study chair. Patients also undergo blood sample collection and CT, MRI, or PET/CT throughout the trial. Patients also undergo tumor biopsy throughout the trial.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Patients must have histologically or cytologically confirmed colorectal adenocarcinoma
Patients must have unresectable or metastatic measurable disease on imaging for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determination within 28 days of registration
For patients enrolling to the expansion cohort, lesions must be amenable to research biopsy
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CA-4948 (emavusertib) and FOLFOX in combination with bevacizumab in patients < 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥ 60%)

Key exclusion criteria (19 listed)

Patients with high-frequency microsatellite instability (MSI-H) or deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) colorectal cancer at pre-enrollment screening
Patients with prolonged QT interval by Fridericia's correction formula (QTcF) (> 450ms) on screening electrocardiogram (ECG)
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia
Patients who are receiving any other investigational agents
Patients who have received prior treatment with any chemotherapy (either in the adjuvant or metastatic setting), including FOLFOX, fluorouracil/leucovorin/irinotecan (FOLFIRI), folinic acid/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI), or antiangiogenic agents such as bevacizumab and similar agents, are not eligible for this study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BevacizumabAlso: ABP 215, ABP-215, ABP215, AlymsysGiven IV	Biological	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo tumor biopsy	Procedure or surgery	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection	Procedure or surgery	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT or PET/CT	Procedure or surgery	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
EmavusertibAlso: AU 4948, AU-4948, CA 4948, CA-4948Given PO	Biological	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
FluorouracilAlso: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedioneGiven IV	Drug	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven IV	Drug	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI	Procedure or surgery	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
OxaliplatinAlso: 1-OHP, Ai Heng, Aiheng, DacotinGiven IV	Drug	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)
Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET/CT	Procedure or surgery	Group A (CA-4948, bevacizumab, FOLFOX), Group B (CA-4948, bevacizumab, FOLFOX)

Primary outcome

Dose limiting toxicities (DLT)
Time frame: Up to 2 cycles (Cycle length = 14 days)
DLT will be based on the first 2 cycles (28 days) of emavusertib.
Incidence of treatment-emergent adverse events
Time frame: Up to 2 cycles (Cycle length = 14 days)
The adverse events will be recorded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

6 secondary outcomes

Incidence of adverse events
Time frame: Baseline to 30 days after last dose of study drug
Overall response rate
Time frame: From the start of treatment until disease progression/recurrence, assessed up to 12 months after end of treatment
Progression free survival
Time frame: From first dose to the earlier date of assessment of progression or death by any cause in the absence of progression, assessed up to 12 months after end of treatment
Overall survival
Time frame: From the date of first dose to the date of death by any cause, assessed up to 12 months after end of treatment
Disease control rate
Time frame: Up to 12 months after end of treatment
Molecular profiling
Time frame: At baseline, between cycle (C) 1 day (D) 10 and C1D14, and disease progression

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

UF Health Cancer Institute - Gainesville

Gainesville, United States

352-273-8010

cancer-center@ufl.edu

Memorial Hospital East

Shiloh, United States

314-747-9912

dschwab@wustl.edu

University of Kansas Clinical Research Center

Fairway, United States

913-588-3671

KUCC_Navigation@kumc.edu

Susanna V Ulahannan principal investigator

Yale University Cancer Center LAO

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 22 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLT) (time frame: Up to 2 cycles (Cycle length = 14 days)). The study lists 2 primary outcomes in all. 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 NCT06696768.

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 9 Sep 2026.