A Study Of ART0380 For The Treatment Of Advanced Or Metastatic Solid Tumors

Study Overview

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors

This clinical trial is evaluating a drug called ART0380 in participants with advanced or metastatic solid tumors. The main goals of this study are to: * Find the recommended dose of ART0380 that can be given safely to participants alone and in combination with gemcitabine or irinotecan * Learn more about the side effects of ART0380 alone and in combination with gemcitabine or irinotecan * Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine or irinotecan

ART0380 is a new investigational medicinal product that is a potent and selective inhibitor of Ataxia telangiectasia and Rad3-related (ATR). ART0380 is being developed as an oral anti-cancer agent for the treatment of participants with cancers that harbor defects in deoxyribonucleic acid (DNA) repair and in combination with agents including those that cause DNA damage. This study is an open-label Phase I/IIa study designed to evaluate the safety, tolerability, PK and preliminary efficacy of ART0380 as monotherapy or in combination with gemcitabine or irinotecan in participants with advanced or metastatic solid tumors, advanced or solid tumors that fail to express Ataxia-Telangiectasia Mutated protein kinase (ATM) by immunohistochemistry, and high grade serous ovarian, primary peritoneal or fallopian tube carcinoma.

Advanced Cancer
Metastatic Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Fallopian Tube Cancer
Endometrial Cancer
Metastatic Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
Acinar Cell Carcinoma

DRUG: ART0380
DRUG: Gemcitabine
DRUG: Irinotecan

ART0380C001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-12-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-05
First Submitted that Met QC Criteria 2020-12-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-08
First Posted (ACTUAL) 2020-12-08	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part A1 Part A1 will evaluate intermittent and continuous dosing of ART0380 monotherapy. Treatment will be given in 21-day cycles. Up to 50 participants will participate in this dose-escalation arm.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles.
EXPERIMENTAL: Part A2 Part A2 will evaluate intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles. Up to 21 participants will participate in this dose escalation arm.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Gemcitabine Gemcitabine will be administered on Days 1 and 8 of a 21-day cycle.
EXPERIMENTAL: Part A3 Part A3 will evaluate intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles. Up to approximately 60 participants will participate in this dose escalation arm.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Irinotecan Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.
EXPERIMENTAL: Part B1 In Part B1, up to 7 cohorts making up to a total of approximately 166 participants with solid cancers with alterations in the ATM (ataxia-telangiectasia mutated) gene likely to predict for loss of ATM protein will be treated with either * ART0380 monothe	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Irinotecan Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.
EXPERIMENTAL: Part B2 In Part B2, up to 60 participants with high grade serous ovarian, primary peritoneal, or fallopian tube carcinoma will be randomized (open label) 1:1 to either ART0380 in combination with gemcitabine or gemcitabine alone.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Gemcitabine Gemcitabine will be administered on Days 1 and 8 of a 21-day cycle.
EXPERIMENTAL: Part B3 in Part B3, up to 40 participants with persistent or recurrent endometrial cancer (EC) will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle..	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles.
EXPERIMENTAL: Part B4 In Part B4, up to 40 participants with advanced or metastatic solid tumors will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles.
EXPERIMENTAL: Part B5 In Part B5, up to 80 participants with colorectal cancer (CRC) will receive ART0380 in combination with irinotecan on a 21-day cycle.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Irinotecan Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.
EXPERIMENTAL: Part B6 In Part B6, up to 80 participants with pancreatic ductal adenocarcinoma (PDAC) or acinar cell carcinoma will receive ART0380 in combination with irinotecan on a 21-day cycle.	DRUG: ART0380 Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles. DRUG: Irinotecan Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.

Primary Outcome Measures	Measure Description	Time Frame
Part A: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities (DLTs) from ART0380 monotherapy and in combination with gemcitabine or irinotecan		From Cycle 0 Day -2 to Cycle 1 Day 21. Each cycle is 21 days.
Parts B1/B3/B4/B5/B6: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan	Safety reported as incidence of adverse events	From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380. Each cycle is 21 days.
Part B2: Progression free survival by RECIST 1.1 in participants receiving ART0380 in combination with gemcitabine or gemcitabine alone	Progression free survival (PFS)	Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.

Secondary Outcome Measures	Measure Description	Time Frame
Part B2: Number of participants with adverse events following administration of ART0380 in combination with gemcitabine or gemcitabine alone		From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or gemcitabine. Each cycle is 21 days.
Pharmacokinetic Analysis (single dose): determine the plasma concentration of ART0380 when given alone and in combination		PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Pharmacokinetic Analysis (multiple dose): determine the plasma concentration of ART0380 when given alone and in combination		PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Pharmacokinetic Analysis: Renal clearance of ART0380		Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.
Parts A1, A2, A3, B1, B2, B3, B4, B5, and B6: Objective response rate based on RECIST 1.1		Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Parts A1, A2, A3, B1, B2, B3, B4, B5, and B6: Duration of response based on RECIST 1.1		Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Parts A1, A2, A3, B1, B2, B3, B4, B5, and B6: Progression free survival based on RECIST 1.1		Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Assess tumor biopsies by immunohistochemistry (IHC) for loss of Ataxia Telangiectasia Mutated (ATM) protein	Where available archival tumor samples will be obtained for analysis of loss of ATM protein by IHC. If an archival tumor sample is not available, a pre-dose tumor biopsy must be taken.	Prior to dosing on Cycle 1 Day 1
Pharmacokinetic Analysis (single and multiple dose where the data allow)	Where available, determine the plasma concentration of irinotecan and its metabolite	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Time to Maximum plasma concentration of Irinotecan and ART0380		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Estimated Renal Clearance of Irinotecan and ART0380		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-infinity)		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve from zero to 12 hours (AUC0-12)		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under the Plasma Concentration Time Curve from zero to 24 hours (AUC0-24)		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the curve concentration-time curve over the dosing interval (AUC(0-infinity))		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: The Volume of Distribution based on the terminal Phase (Vz)		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the Plasma concentration time curve from zero to the end of the dosing interval (AUCtau)		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Maximum plasma Concentration (Cmax) in a fasting and fed state.		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Time to Maximum plasma concentration (Tmax) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve from zero to the time of last plasma concentration (AUC0-t) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Terminal half-life (t1/2) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-tau)) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve over the last 12-h dosing interval (AUC012) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-infinity)) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve for Oral Clearance (CL/F) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve for Volume of Distribution (Vz/F) in a fasting and fed state		PK will be measured during Cycle 1. Cycle 1 is 21 days

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Sarah Cannon Development Innovations

Phone Number: 844-710-6157

Email: SCRI.InnovationsMedical@scri.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed informed consent
Have not received a previous treatment targeting the ATR/CHK1 pathway
Discontinued all previous treatments for cancer for at least 21 days or 5 half-lives, whichever is shorter, and recovered from the acute effects of therapy to CTCAE Grade ≤1. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
If patients have a known germline BRCA mutation or a cancer with a somatic BRCA mutations or which is HRD positive and for which there is an approved PARP inhibitor, participants should have received such treatment before participating in the study unless contra-indicated
At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 Guidelines (PCWG-3)
Acceptable hematologic, renal, hepatic, and coagulation functions independent of transfusions and granulocyte colony-stimulating factor
Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis.
Female patients of childbearing potential and male patients with female partners of childbearing potential are required to use highly effective contraception plus one barrier method during their participation in the study and for 7 months and 5 months respectively following the last dose. For male and female patients given gemcitabine or irinotecan, highly effective contraception plus one barrier method must be used from study entry until 6 months after the last dose of study treatment. Male patients are required to refrain from donating sperm and female patients are required to refrain from donating eggs, during their participation in the study and for 6 months following last dose.
Estimated life expectancy of ≥12 weeks
Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Advanced or metastatic cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study
Performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale

Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior treatment with gemcitabine is permitted.
Performance status of 0-1 on the ECOG scale

Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
Performance status of 0-1 on the ECOG scale
For food effect cohort only: Patients must be able to eat a high-fat meal within a 30 minute period, as provided by the study site.

Patients with advanced or metastatic solid tumors with alterations to the ATM gene likely to predict for loss of ATM protein
Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
Performance status of 0-1 on the ECOG scale
For France only ART0380 Monotherapy; Patient that is not eligible for curative treatment, for whom all standard of care therapies have failed and no therapies known to provide clinical benefit are available.
Combination arms; Patients for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
For Spain only ART0380 Combination therapy, Patient that is not eligible for curative treatment, for whom standard of care therapies have failed.

Patients with a known germline BRCA mutation, or a cancer with a known somatic BRCA mutation, or which is known to be HRD positive, and for which there is an approved PARP inhibitor should have received such treatment before participating in the study, unless contra-indicated.
Females with histologically-confirmed diagnosis of high grade serous carcinoma of the ovary, fallopian tube or primary peritoneum that is not amenable to curative therapy
Platinum-resistant disease, defined as disease progression within 6 months of last receipt of platinum-based chemotherapy. Patients must not have had primary platinum-refractory disease (disease that progressed during first-line platinum-based therapy).
No more than one prior regimen in the platinum-resistant setting. Hormonal therapies and antiangiogenic therapies (as single agents) and PARP inhibitors used as maintenance therapy are not considered as separate lines of therapy. Patients should have previously received bevacizumab and chemotherapy unless contra-indicated.
Have not received prior treatment with gemcitabine unless administered in combination with a platinum with no disease progression within 12 months after completion of that regimen
Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
Performance status of 0-1 on the on the ECOG scale

Persistent or recurrent endometrial cancer with biological selection.:
Patients should have received taxane/platinum chemotherapy, unless contraindicated.
Measurable disease.
Performance status of 0-1 on the ECOG scale.

Advanced or metastatic solid cancers of any histology with biological selection
If a PD-1/PDL-1 inhibitor (eg, pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study.
Radiologically evaluable disease
Performance status of 0-1 on the ECOG scale

Metastatic CRC with alterations to the ATM gene
Participants should have previously received appropriate prior lines of therapy in this setting.
Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1.
Performance status of 0-1 on the ECOG scale.

Metastatic or locally advanced PDAC or acinar cell carcinoma with alterations to the ATM gene
Participants should have previously received prior lines of therapy in this setting
Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1
Performance status of 0-1 on the ECOG scale
Serum albumin ≥3g/dL within 7 days prior to first dose.

Women who are pregnant, breast feeding, or who plan to become pregnant while in the study or within 7 months after the last administration of study treatment
Men who plan to father a child while in the study or within5 months after the last administration of study treatment
Serious concomitant systemic disorder that would compromise the participants ability to adhere to the protocol including: one or more opportunistic HIV/AIDs-related infections within the past 12 months, a known hepatitis B virus, or known hepatitis C virus; documented active or chronic tuberculosis infection; malignancy prior to the one currently being treated that is not in remission
Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
Moderate or severe cardiovascular disease
Valvulopathy that is severe, moderate, or deemed clinically significant
Documented major electrocardiogram (ECG) abnormalities which are clinically significant
Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment
Received a live vaccine within 30 days before the first dose of study treatment
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
Recent major surgery within 4 weeks prior to entry into the study or minor surgery within 1 week of entry into the study
Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
Currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

Patients who have symptoms or signs of clinically unacceptable deterioration of the primary disease at the time of screening.
Patients receiving inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment
Part B5 only: Patients who have received fruquintinib or regorafenib or trifluridine/tipiracil.
Part A3 Fed-fasted cohort only: Patients receiving acid reducing agents within 1 week before the first dose of study treatment will be excluded
Part B6 only: Neuroendocrine (carcinoid, islet cell) or adenosquamous carcinoma pancreatic cancer

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Melissa Johnson, MD, Tennessee Oncology

Publications

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