New drug combo aims to stall advanced cancers
NCT ID NCT05691491
First seen Jun 27, 2026 · Last updated Jul 31, 2026 · Updated 3 times
Summary
This early-phase trial tests a combination of two drugs—temozolomide and M1774—in people with advanced solid tumors that have spread. Temozolomide damages cancer cell DNA, while M1774 blocks enzymes that help cancer grow. The goal is to find the best dose and see if the combo can shrink or stabilize tumors longer than temozolomide alone. About 42 participants are being recruited.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- temozolomide and M1774
- What this could lead to
- If it works, this could offer a new treatment option for people with advanced solid tumors that have spread, potentially shrinking or stabilizing their cancer for longer.
- What could go wrong
- This is an early-phase trial with only 42 participants, so the benefits are unproven. The drug combo may cause side effects or fail to control the cancer.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 42 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Sep 2023
- Expected to finish
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Mar 2027
An estimate. End dates often move.
- Lead sponsor
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A government research agency
The lead sponsor is the US National Institutes of Health.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of metastatic advanced cancer. * In dose escalation, any solid tumor patients with either O6-methylguanine DNA methyltransferase (MGMT) promoter hypermethylation positivity on testing / pre-screening of archival tissue OR an extracranial solid tumor where TMZ is considered a standard of care per National Comprehensive Cancer Network (NCCN) guidelines (neuroendocrine tumor, small cell lung cancer, melanoma or soft tissue sarcoma). The tumor lesion must be safely accessible to a mandatory biopsy. Patients with MGMT promoter hypermethylated colorectal cancer must be mismatch repair proficient / microsatellite stable. * In phase 2, only patients with mismatch repair proficient / microsatellite stable colorectal cancer that have MGMT promoter hypermethylation positivity on pre-screening of archival tissue will be eligible. * In dose escalation, patients must have progressed after treatment with all available therapies including immunotherapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Patients may not have previously received temozolomide or an ataxia telangiectasia and rad3-related (ATR) inhibitor. * For patients with mismatch repair proficient / microsatellite stable colorectal cancer in the phase 2 portion, patients must have received prior therapy with 1 or more systemic therapies in the metastatic setting that includes 5-fluorouracil, irinotecan, and oxaliplatin. Patients with microsatellite stable colorectal cancer (mCRC) need to have had exposure, unless contraindicated, to all 3 of oxaliplatin, irinotecan, and fluoropyrimidine (FP). The use of 5-fluorouracil and oxaliplatin in the adjuvant setting is acceptable, provided the development of metastatic disease was less than 6 months after the completion of adjuvant therapy. Patients with a prior hypersensitivity reaction to oxaliplatin in the adjuvant setting do not require retreatment in the metastatic setting. * Age \>=18 years. Because no dosing or adverse event data are currently available on the use of M1774 in combination with temozolomide in patients \< 18 years of age, children are excluded from this study. * Measurable disease on CT and/or MRI per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%). * Hemoglobin \>=10 g/dL (No blood transfusions are allowed within 14 days of cycle 1 day 1 \[C1D1\]). * White blood cells (WBC) \> 3 x 10\^9/L. * Absolute neutrophil count \>= 1,500/mcL. * Platelets \>= 100,000/mcL. * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN). * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine-aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN except for when liver metastases are present, in which case they must be =\< 5 x institutional ULN. * Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2. * 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 for 4 weeks. * 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 2B or better. * The effects of M1774 on the developing human fetus are unknown. For this reason and because ATR inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of M1774 administration. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of M1774 administration. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * 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 and neuropathy, which may be =\< grade 2. * History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to M1774 or temozolomide, including dacarbazine. * Patients with uncontrolled intercurrent illness. * Pregnant women are excluded from this study because M1774 is an ATR inhibiting agent 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 M1774 breastfeeding should be discontinued if the mother is treated with M1774. These potential risks also apply to temozolomide. * Patients with a prior history of ataxia telangiectasia. * Patients who are not able to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication. * Patients who cannot discontinue proton-pump inhibitors (PPIs) while taking M1774. H-2 receptor antagonists are allowed but should not be taken within 12 hours before or 2 hours after M1774. Antacids are also allowed, but should not be taken 2 hours before 2 hours after M1774. * Extensive RT involving greater than 30% of the bone marrow is not permitted during the study. * A Fridericia's correction formula (QTcF) \> 480 ms is exclusionary given the potential for QT.
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Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The study's own enquiry address
This study publishes an address for enquiries. See it below .
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The places running it
16 sites. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Show contact details
Enter your email to view the contact information for this study.
Genom att skicka in godkänner du våra Användarvillkor
Locations
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Memorial Hospital East
ACTIVE_NOT_RECRUITINGShiloh, Illinois, 62269, United States
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National Cancer Institute Developmental Therapeutics Clinic
RECRUITINGBethesda, Maryland, 20892, United States
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Siteman Cancer Center at Christian Hospital
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63136, United States
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Siteman Cancer Center at Saint Peters Hospital
ACTIVE_NOT_RECRUITINGCity of Saint Peters, Missouri, 63376, United States
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Siteman Cancer Center at West County Hospital
ACTIVE_NOT_RECRUITINGCreve Coeur, Missouri, 63141, United States
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Siteman Cancer Center-South County
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63129, United States
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Smilow Cancer Hospital Care Center-Trumbull
RECRUITINGTrumbull, Connecticut, 06611, United States
Contact Email: •••••@•••••
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UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITINGOrange, California, 92868, United States
Contact Email: •••••@•••••
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UC San Diego Moores Cancer Center
ACTIVE_NOT_RECRUITINGLa Jolla, California, 92093, United States
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UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITINGIrvine, California, 92612, United States
Contact Email: •••••@•••••
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UPMC Hillman Cancer Center
RECRUITINGPittsburgh, Pennsylvania, 15232, United States
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University of Kansas Cancer Center
RECRUITINGKansas City, Kansas, 66160, United States
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University of Kansas Cancer Center - Lee's Summit
RECRUITINGLee's Summit, Missouri, 64064, United States
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University of Kansas Cancer Center - North
RECRUITINGKansas City, Missouri, 64154, United States
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University of Kansas Cancer Center at North Kansas City Hospital
SUSPENDEDNorth Kansas City, Missouri, 64116, United States
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University of Kansas Cancer Center-Overland Park
RECRUITINGOverland Park, Kansas, 66210, United States
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University of Kansas Clinical Research Center
RECRUITINGFairway, Kansas, 66205, United States
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University of Kansas Hospital-Indian Creek Campus
RECRUITINGOverland Park, Kansas, 66211, United States
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University of Kansas Hospital-Westwood Cancer Center
RECRUITINGWestwood, Kansas, 66205, United States
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University of Oklahoma Health Sciences Center
RECRUITINGOklahoma City, Oklahoma, 73104, United States
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Vanderbilt University/Ingram Cancer Center
RECRUITINGNashville, Tennessee, 37232, United States
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Washington University School of Medicine
ACTIVE_NOT_RECRUITINGSt Louis, Missouri, 63110, United States
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Yale University
RECRUITINGNew Haven, Connecticut, 06520, United States
Contact Email: •••••@•••••
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