Testing the Addition of an Anticancer Drug, BAY 1895344, to the Usual Chemotherapy With FOLFIRI in Advanced or Metastatic Cancers of the Stomach and Intestines

Running, not enrolling · Phase 1

Conditions studied: Advanced Colorectal Carcinoma, Advanced Digestive System Carcinoma, Advanced Gastric Carcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Colorectal Carcinoma, Metastatic Digestive System Carcinoma, Metastatic Gastric Carcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8

In brief

This phase I trial investigates the best dose, possible benefits and/or side effects of BAY 1895344 in combination with FOLFIRI in treating patients with stomach or intestinal cancer that that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as irinotecan, fluorouracil, and leucovorin, (called FOLFIRI in short) 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. Giving BAY 1895344 in combination with FOLFIRI may help shrink advanced or metastatic stomach and/or intestinal cancer.

Key facts

Study ID: NCT04535401
Run by: National Cancer Institute (NCI)
People needed: 10
Starts: 2021-08-13
Expected to finish: 2026-07-01
Last updated by the study team: 2026-07-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

For Dose Escalation: Patients must have histologically or cytologically confirmed advanced or metastatic gastrointestinal (GI) cancers with Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1) measurable disease who have progressed on at least one prior treatment for metastatic disease and for whom FOLFIRI is considered a reasonable treatment option. Patients with mismatch repair deficiency should have progressed on immunotherapy
For Dose Expansion: Patients must have either:
Colorectal cancer who have previously progressed on irinotecan and tolerated an irinotecan dose equal to or greater than the recommended phase 2 dose (RP2D). If they have mismatch repair deficiency they should have progressed on immunotherapy OR
Gastroesophageal cancer who have progressed on at least one first-line therapy for metastatic disease. If they have mismatch repair deficiency they should have progressed on immunotherapy
For Dose Expansion: Patients be willing to undergo biopsies for research purposes only. The accessible tumor can be the primary or metastatic tumor site. Both research biopsies should be taken from the same tumor site
Patients must have progressive disease on at least first-line therapy for metastatic disease. Previous treatment with irinotecan is allowed
Age >= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 1895344 in combination with FOLFIRI in patients <18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status =< 1
Leukocytes >= 3,000/mcL
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 glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m\^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
International normalization ratio (INR) =< 1.5 × ULN unless participant is receiving anticoagulant therapy, in which case prothrombin time (PT) or activated partial thromboplastin time (aPTT) should be within expected therapeutic range of anticoagulants. If patient has a new diagnosis of venous thromboembolism (VTE), then patient should be appropriately anticoagulated with low molecular weight heparin (LMWH) or direct acting oral anticoagulants (DOACs) and be clinically stable for at least 1 week post treatment onset
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy, that does not interact with study 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 that does not interact with study 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 and HCV therapy does not interact with study therapy
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 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 BAY 1895344 on the developing human fetus are unknown. For this reason and because DNA-damage response inhibitors agents as well as other therapeutic agents used in this trial, 5-FU and irinotecan, are known to be teratogenic, 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 and for 6 months after completion of BAY 1895344 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 6 months after completion of study treatment administration
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

You may not qualify if…

Patients with a history of prior treatment with an ATR inhibitor
Patients with a history of other malignancy that could affect compliance with the protocol or interpretation of the results
Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
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
History of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 1895344, 5-FU, leucovorin, or irinotecan. Patient eligibility can be discussed with the primary investigator (PI) if prior reactions do not seem to warrant excluding the patient
Patients receiving any medications that are substrates of CYP3A4 with a narrow therapeutic window or strong inhibitors/inducers of CYP3A4 are ineligible, if they cannot be transferred to alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Patients with uncontrolled intercurrent illness
Patients with psychiatric illness/social situations that would limit compliance with study requirements
Gastrointestinal pathology or history that adversely impact the ability to take or absorb oral medication
Pregnant women are excluded from this study because BAY 1895344 as a DNA-damage response inhibitor may have 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 BAY 1895344 breastfeeding should be discontinued if the mother is treated with BAY 1895344 and for 4 months after end of treatment. These potential risks may also apply to other agents used in this study
Patients who were unable to tolerate prior irinotecan treatment are excluded from this study
Patients with a corrected QT (QTc) interval >= 470 msec are excluded from this study

Where it is running

City of Hope Comprehensive Cancer Center — Duarte, California, United States
National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States
National Institutes of Health Clinical Center — Bethesda, Maryland, United States
Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
Washington University School of Medicine — St Louis, Missouri, United States
Siteman Cancer Center-South County — St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital — St Louis, Missouri, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States

Full record on ClinicalTrials.gov

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