What side effects are associated with this type of intervention?

Common treatments for lung cancer, including chemotherapy drugs like irinotecan and topotecan, often cause side effects such as nausea, vomiting, diarrhea, fatigue, and myelosuppression. Enzyme inhibitors, which target specific enzymes necessary for cancer cell growth, can lead to side effects like fatigue, nausea, increased liver function tests, and other toxicities specific to the targeted enzyme pathways.

What prior FDA approvals exist?

Several FDA-approved drugs target specific enzymes in the treatment of lung cancer. Sotorasib and adagrasib are approved for KRAS G12C-mutated non-small cell lung cancer (NSCLC), inhibiting the KRAS G12C enzyme. Additionally, selpercatinib and pralsetinib are approved for RET fusion-positive NSCLC, targeting the RET kinase. These drugs exemplify the enzyme inhibition approach in lung cancer treatment, similar to the investigational drug BAY 1895344, which is being studied for its potential to inhibit enzymes necessary for tumor cell growth.

What other types of research exist?

Promising novel alternatives to BAY 1895344 for lung cancer patients include: 1) LY01008, a bevacizumab biosimilar, combined with paclitaxel/carboplatin, which has shown similar efficacy and safety to Avastin in advanced non-squamous NSCLC. 2) Alectinib and ceritinib for ALK-positive NSCLC, which have demonstrated clinical benefits in phase III trials. 3) Immune checkpoint inhibitors like pembrolizumab, which have shown durable responses in advanced NSCLC with PD-L1 expression.

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Topoisomerase I inhibitor

BAY 1895344 + Chemotherapy for Lung Cancer

Phase 1

Waitlist Available

Led By Satya Das

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a solid tumor for which irinotecan or topotecan is considered standard of care

Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2

Must not have

Patients with uncontrolled intercurrent illness

Patients with an uncontrolled infection requiring IV antibiotics

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 months post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of a new drug combined with chemotherapy in patients with advanced solid tumors. The goal is to see if this combination can slow tumor growth more effectively than chemotherapy alone. The new drug blocks enzymes needed for tumor growth, while the chemotherapy drugs kill or stop the tumor cells from dividing. The chemotherapy drugs used in this trial are known to be effective in treating various cancers.

Who is the study for?

Adults with advanced solid tumors, specifically small cell lung cancer, neuroendocrine carcinoma, or pancreatic cancer that have worsened after standard treatment. Must be able to swallow pills and not have severe heart disease. Eligible even if HIV-positive or with treated hepatitis B/C as long as it's under control. Cannot join if pregnant/breastfeeding or on certain drugs affecting liver enzymes.

What is being tested?

The trial is testing the effectiveness of adding a new anti-cancer drug called BAY 1895344 to usual chemotherapy (irinotecan or topotecan). The goal is to see if this combination can better halt tumor growth compared to standard chemotherapy alone in patients with specific advanced cancers.

What are the potential side effects?

Possible side effects include reactions related to the immune system, fatigue, digestive issues like nausea and diarrhea from chemotherapy, potential liver enzyme changes due to BAY 1895344, and other common chemo-related symptoms such as hair loss.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer treatment includes irinotecan or topotecan.

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My kidney function, measured by GFR, is normal or above 60.

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My cancer has spread, can't be surgically removed, and has worsened after treatment.

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I have at least one tumor that can be measured, not including the one to be biopsied.

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I am 18 years old or older.

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My hepatitis B virus load is undetectable with treatment.

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My brain scans show no worsening after treatment for brain metastases and I have no symptoms.

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I have advanced lung, neuroendocrine, or pancreatic cancer that has worsened after treatment.

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I had hepatitis C but have been treated and cured.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any unmanaged ongoing illnesses.

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I have an infection that needs IV antibiotics.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 months post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 months post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 months post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) (Dose Escalation Phase)

Occurrence of grade 4 hematologic AEs (Dose Expansion Phase)

Secondary study objectives

Area under the concentration-time curve (AUC)

Changes in tumor expression patterns of gamma-H2AX

Changes in tumor expression patterns of pS343-NBS1

+5 more

Other study objectives

Tumor ATM expression loss

Tumor deoxyribonucleic acid damage response (DDR) gene mutations present

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort III (elimusertib, topotecan)Experimental Treatment6 Interventions

Patients receive elimusertib PO QD on days 2 and 5 and topotecan IV over 30 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

Group II: Cohort II (elimusertib, irinotecan)Experimental Treatment6 Interventions

Patients receive elimusertib PO QD on days 2, 3, 9, 10, 16, and 17 of cycle 1 and 2, and on days 2, 3, 9, and 10 of each cycle thereafter. Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 of cycle 1 and 2, and on days 1 and 8 of each cycle thereafter. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

Group III: Cohort I (elimusertib, irinotecan)Experimental Treatment6 Interventions

Patients receive elimusertib PO BID on days 1 and 2 and irinotecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Irinotecan Hydrochloride

2010

Completed Phase 3

~2050

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Topotecan Hydrochloride

2013

Completed Phase 3

~6270

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for lung cancer include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs like irinotecan and topotecan work by interfering with DNA replication, thereby killing rapidly dividing cancer cells. Targeted therapies, such as tyrosine kinase inhibitors (e.g., osimertinib for EGFR mutations), block specific enzymes involved in cancer cell growth and survival. Immunotherapies, like PD-1/PD-L1 inhibitors, enhance the immune system's ability to recognize and destroy cancer cells. Enzyme inhibition, as studied with BAY 1895344, is crucial because it can halt tumor growth by blocking essential enzymes needed for cancer cell proliferation. This targeted approach can potentially lead to more effective treatments with fewer side effects, improving outcomes for lung cancer patients.