Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors

NCT04616534 | Active Not Recruiting Phase 1 Results FDA Drug

• 3 other identifiers: NCI-2020-0837010403UM1CA186709
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344) in treating patients with pancreatic, ovarian, and other solid tumors that have spread to other places in the body (advanced). Gemcitabine is a chemotherapy drug that blocks the cell from making DNA and may kill tumor cells. elimusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and elimusertib in combination may shrink or stabilize cancer.

Conditions

Advanced Fallopian Tube Carcinoma; Advanced Malignant Solid Neoplasm; Advanced Pancreatic Adenocarcinoma; Advanced Primary Peritoneal Carcinoma; Fallopian Tube High Grade Serous Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Ovarian High Grade Serous Adenocarcinoma; Platinum-Resistant Fallopian Tube Carcinoma; Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Fallopian Tube Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Fallopian Tube Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage III Primary Peritoneal Cancer AJCC v8; Stage IV Primary Peritoneal Cancer AJCC v8; Unresectable Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8; Advanced Ovarian Carcinoma

Outcome Measures

Primary Outcomes (6)

• Number of Patients on Treatment With Related Adverse Events

  The toxicity of the combination of gemcitabine plus elimusertib will be assessed with Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 criteria. The safety and tolerability were evaluated using the number of treatment-related adverse events.

  Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024) (3 years and 4 months). Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days.

• Maximum Tolerated Dose (MTD)

  A conventional algorithm (3+3 design) will be used to identify the MTD, escalating on zero of three or one of six dose-limiting toxicities (DLTs), and de-escalating if two DLTs are encountered. The MTD will be the highest dose level at which zero of three or one of six subjects experience a DLT. The MTD was not reached due to toxicity experienced during cycle 1.

  The MTD was evaluated during the dose-escalation phase, occurring from the first patient on treatment (Jun '21) through the last patient's last dose (Sep '24) (3 years and 3 months). MTD was evaluated for a median of 58.5 days, ranging 28 - 285 days.

• Overall Response Rate (ORR)

  Radiological response will be assessed with Response Evaluation Criteria in Solid Tumors 1.1 criteria and will be portrayed as the percentage of subjects with a complete response (CR) and partial response (PR).

  ORR was assessed from the time of the first patient on study (June 2021) through the last patient off study (October 2024). ORR was calculated for a median of 103 days, ranging from 30 - 312 days.

• Duration of Response

  Duration of response was assessed from the time of the first patient on treatment (June 2021) through the last patient off study (October 2024). Duration of response was calculated for a median of 103 days, ranging from 30 - 312 days.

• Progression Free Survival (PFS)

  PFS was evaluated from the first patient on study (Jun '21) through the last patient's death or date of progressive disease (Sep '24) (3 years and 3 months). PFS was calculated for a median of 90 days, ranging 25 - 286 days.

• Overall Survival

  Overall survival (OS) was evaluated from the first patient on study (June 2021) through the last patient's death or off study date (October 2024).

  OS was calculated for a median of 103 days, ranging from 30 - 312 days.

Secondary Outcomes (9)

• Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine

  Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant.

• Gemcitabine Pharmacokinetics

  Days 1 and 8 of cycle 1 dose-escalation (first patient's day 1, June 2021, to last patient's day 8, December 2023) equaling the total collection time of 2 year and 6 months. Samples were collected on two days for each participant.

• Presence or Absence of Homologous Recombination (HR) Repair Proficiency (Dose Expansion)

  Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort

• Presence or Absence of ATR Activation (Dose Expansion)

  Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort

• Increase in Deoxyribonucleic Acid (DNA) Damage Level (Dose Expansion)

  Pre-treatment and on-treatment in the dose expansion cohort

Study Arms (1)

Treatment (gemcitabine, elimusertib)

EXPERIMENTAL

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and elimusertib QD or PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial and collection of blood samples during screening and on days 1, 2, and 9-10 of cycle 1. Patients in the dose-expansion portion of the trial also undergo biopsies during screening and on day 9 of cycle 1.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Diagnostic Imaging Testing; Drug: Elimusertib; Drug: Gemcitabine

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy (dose expansion cohort only)

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (gemcitabine, elimusertib)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (gemcitabine, elimusertib)

Diagnostic Imaging Testing PROCEDURE

Undergo medical imaging scans

Also known as: Diagnostic Imaging, Medical Imaging

Treatment (gemcitabine, elimusertib)

Elimusertib DRUG

Given PO

Also known as: ATR Inhibitor BAY1895344, ATR Kinase Inhibitor BAY1895344, BAY 1895344, BAY-1895344, BAY1895344

Treatment (gemcitabine, elimusertib)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (gemcitabine, elimusertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DOSE ESCALATION COHORT:
• Patients must have histologically confirmed solid tumor malignancy that is not curable with standard approaches. Gemcitabine must be considered a standard therapy for the participant's malignancy
• Patients must have a measurable disease, in at least one lesion, for both the dose escalation and expansion cohorts, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Patients must have received one line of treatment for their incurable cancer before enrolling in this trial. Patients with rare malignancies for which there is no accepted standard chemotherapy regimen can enroll without any prior treatments
• Patients must not have received more than two lines of cytotoxic chemotherapy
• Patients can have received prior gemcitabine
• Adjuvant chemotherapy is counted as one line of treatment if patients received it within 6 months of their cancer recurring
• There is no limit for lines of prior targeted therapies or immunotherapy
• Patients who received a prior PARP inhibitor must have had progressive disease, or intolerable toxicity, on the PARP inhibitor prior to enrolling on the study
• DOSE EXPANSION COHORT:
• Participants must have a histologically confirmed advanced pancreatic adenocarcinoma or ovarian cancer (high grade serous ovarian, primary peritoneal or fallopian tube cancer) that is not curable with standard approaches. Patients with both metastatic pancreatic cancer and unresectable pancreatic cancer are eligible
• Ovarian cancer:
• Patients with ovarian cancer must have platinum-resistant disease, defined as progression within 6 months after the last platinum regimen
• Patients with ovarian cancer cannot have received more than one prior regimen in the platinum-resistance setting
• Pancreatic cancer:

You may not qualify if:

• Patients cannot receive chemotherapy, targeted therapy or immunotherapy within 3 weeks of study entry
• Patients who have had radiotherapy within 4 weeks 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 and lymphopenia
• Participants must not have received investigational therapy administered =\< 4 weeks or within a time interval less than at least five half-lives of the investigational agent, whichever is longer, before initiation of protocol therapy
• Participants with known untreated brain metastases are excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to elimusertib (BAY 1895344) or gemcitabine
• 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 including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric illness/social situations that would limit compliance with study requirements are excluded
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because elimusertib (BAY 1895344) as a DNA-damage response inhibitor, and gemcitabine 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 elimusertib (BAY 1895344) breastfeeding should be discontinued if the mother is treated with elimusertib (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 have successfully undergone treatment for another, unrelated clinically relevant cancer, \>= 3 years post final treatment, are eligible to participate in this study
• Patients cannot have received radiation to more than 25% of their hematopoietically active bone marrow. Pelvic radiation is considered to affect 25% of the haematopoietically active bone marrow, and only one prior course of pelvic radiation is allowed (Hayman et al., 2011)
• Patients previously treated with an ATR inhibitor are excluded
• Participants who have undergone major surgery =\< 4 weeks before initiating protocol therapy must have sufficiently recovered from adverse events caused by the procedure, as judged by the treating investigator
• Subjects with a gastrointestinal disorder or malabsorption that could potentially affect the absorption of the study drug are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Biopsy; Specimen Handling; X-Rays; BAY 1895344; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Ovarian Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: James Cleary, MD
• Organization: Dana Farber Cancer Institute

james_cleary@dfci.harvard.edu

6176326073

Study Officials

• James M Cleary

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2020
• First Posted: November 5, 2020
• Study Start: June 1, 2021
• Primary Completion: April 1, 2025
• Study Completion (Estimated): May 20, 2027
• Last Updated: July 31, 2026
• Results First Posted: July 9, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)