BAY 1895344 + Chemotherapy for Lung Cancer

Not currently recruiting at 27 trial locations

Overseen By Thorvardur R. Halfdanarson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Uncontrolled illness, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 14-21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to determine their safety and effectiveness for individuals with certain advanced cancers, including small cell lung cancer, poorly differentiated neuroendocrine cancer, and pancreatic cancer. It combines a new drug, BAY 1895344 (an experimental treatment), with standard chemotherapy drugs, irinotecan or topotecan, to assess their ability to better halt cancer growth. The trial includes different groups that test these combinations in various ways. Suitable candidates for this trial have a solid tumor that has spread, has not responded to other treatments, and can take pills. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new experimental drug.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must stop taking strong CYP3A4 inhibitors at least 1 week before starting irinotecan therapy. It's important to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that adding BAY 1895344, also known as elimusertib, to standard chemotherapy drugs like irinotecan and topotecan may be safe and manageable for patients with advanced solid tumors. In earlier studies, patients who received this combination did not experience severe side effects, although the exact dosage is still being refined.

Elimusertib inhibits certain enzymes that cancer cells need to grow. It is being tested with irinotecan and topotecan, which are chemotherapy drugs that help prevent cancer cells from dividing and spreading. The aim is for elimusertib to enhance the effectiveness of these drugs.

This study is in its early stages, with researchers primarily focused on assessing the treatment's safety. Previous studies have shown that patients can tolerate the combination, but like any treatment, there might be some side effects. These could include common chemotherapy reactions like tiredness or nausea, but the specific effects vary from person to person.

Overall, current data supports the potential safety of BAY 1895344 when used with chemotherapy, but ongoing studies are needed to confirm these findings and determine the best, safest dose for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they offer a unique approach compared to the current standard of care, which often includes platinum-based chemotherapy and immunotherapy. Elimusertib, combined with either irinotecan or topotecan, introduces a novel mechanism by targeting the DNA damage response pathway, potentially enhancing the effectiveness of chemotherapy. The study treatment's varied dosing schedules across different cohorts allow flexibility and precision in managing the disease, aiming to maximize effectiveness while minimizing side effects. These innovative combinations and mechanisms could provide new hope for better outcomes in lung cancer treatment.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that elimusertib, an ATR inhibitor, may help fight small cell lung cancer and gastrointestinal cancers. In this trial, participants in different cohorts will receive elimusertib combined with either irinotecan or topotecan. When paired with irinotecan, elimusertib has demonstrated potential to kill cancer cells in these cancers. Irinotecan is already known to improve survival rates in small cell lung cancer when used with other drugs. Similarly, elimusertib with topotecan shows promise in treating these cancers. Elimusertib works by blocking certain enzymes that cancer cells need to grow, potentially enhancing the effectiveness of chemotherapy drugs in stopping cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Thatcher Heumann

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My cancer treatment includes irinotecan or topotecan.

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

I can swallow pills.

Exclusion Criteria

Breastfeeding women

You have had allergic reactions to drugs like BAY 1895344 or other drugs being used in the study.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive elimusertib and irinotecan or topotecan in cycles, with regular imaging and blood sample collection

14-21 days per cycle

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• BAY 1895344
• Irinotecan Hydrochloride
• Topotecan Hydrochloride

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort III (elimusertib, topotecan) Experimental Treatment 6 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 Treatment 6 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 Treatment 6 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.

Irinotecan Hydrochloride is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Camptosar for:

• Colorectal cancer
• Pancreatic cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer
• Pancreatic cancer

Approved in Canada as Camptosar for:

• Colorectal cancer
• Pancreatic cancer

Approved in Japan as Irinotecan for:

• Colorectal cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Irinotecan, a semisynthetic version of camptothecin, has shown promising activity in treating lung cancer, which has seen stagnant survival rates over the past 20 years.

The article reviews the mechanism of action and development history of irinotecan, highlighting its potential as a new treatment option for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of irinotecan in lung cancer. Fukuoka, M.[2018]

Irinotecan, when combined with cisplatin, significantly improves survival rates in previously untreated patients with extensive-stage small-cell lung cancer, showing a median progression-free survival of 6.9 months compared to 4.8 months with standard treatment (etoposide/cisplatin).

The combination therapy also resulted in a median overall survival of 12.8 months versus 9.4 months for the standard treatment, indicating that irinotecan could be a promising new option for enhancing treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus cisplatin in small-cell lung cancer. Sandler, A.[2018]

Irinotecan (CPT-11) has demonstrated a broad range of antitumor activity across various cancer types, including lymphoma, leukemia, and several solid tumors, although most studies have focused on colorectal and gastrointestinal cancers.

Preliminary results indicate that irinotecan shows modest but reproducible activity in multiple cancers, suggesting the need for further well-designed clinical trials to better understand its efficacy and optimal use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. Rosen, LS.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3076

A phase I study of ATR inhibitor BAY1895344 (elimusertib) ... The ATR inhibitor BAY 1895344 (elimusertib) has demonstrated cytotoxic potential in small cell lung cancer and gastrointestinal cancer ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04514497

Testing the Addition of an Anti-cancer Drug, BAY 1895344, ... This phase I trial tests the safety, side effects and best dose of BAY 1895344 when given together with usual chemotherapy (irinotecan or topotecan) in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9731518/

Quantitation of the ATR inhibitor elimusertib (BAY-1895344 ... Elimusertib (BAY-1895344) is an orally available small molecule ATR inhibitor currently in preclinical and clinical development for cancer treatment.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3077

A phase I study of irinotecan combined with BAY1895344 ... The ATR inhibitor BAY1895344 (elimusertib) has demonstrated cytotoxic potential in SCLC and GI cancer xenografts when combined with Top1 ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-1-2021-913cd

BAY 1895344 + Chemotherapy for Lung Cancer Irinotecan, a component of the treatment, has shown promising results in improving survival rates for small-cell lung cancer when combined with other drugs like ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8048383/

Therapeutic targeting of ATR yields durable regressions in ... Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.