Recruiting
Phase 1
Phase 2

ART0380

Sponsor:

Artios Pharma Ltd

Code:

NCT04657068

Conditions

Advanced Cancer

Metastatic Cancer

Ovarian Cancer

Primary Peritoneal Cancer

Fallopian Tube Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ART0380

Gemcitabine

Irinotecan

Study Details

Brief summary:

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

Conditions

Advanced Cancer

Metastatic Cancer

Ovarian Cancer

Primary Peritoneal Cancer

Fallopian Tube Cancer

Study ID

NCT04657068

Start date

Jan 27, 2021

Status verified date

Jul, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Jan, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

General Inclusion Criteria:

  • Signed informed consent
  • 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
  • Performance status of 0-1 on the ECOG Scale

Additional inclusion criteria for participants in dose escalation (Part A1):

  • 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

Additional inclusion criteria for participants in dose escalation (Part A2):

•Advanced or metastatic cancer for which gemcitabine is an appropriate treatment. Prior treatment with gemcitabine is permitted.

Additional inclusion criteria for participants in dose escalation (Part A3):

  • Advanced or metastatic cancer for which irinotecan is an appropriate treatment. Prior treatment with irinotecan is permitted.
  • 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.

Additional inclusion criteria for participants in dose expansion (Part B1):

  • 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
  • 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.

Additional inclusion criteria for participants in dose expansion (Part B2):

  • 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. 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

Inclusion criteria specific to Part B3

  • Persistent or recurrent endometrial cancer with biological selection.:
  • Patients should have received taxane/platinum chemotherapy, unless contraindicated.
  • Measurable disease.

Inclusion criteria specific to Part B4

  • 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

Inclusion criteria specific to Part B5

  • 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.
  • Patients have received a maximum of 2 prior chemotherapy regimens for the treatment of CRC.
  • Serum albumin ≥3g/dL within 7 days prior to first dose.
  • ECOG Performance Status must be stable for at least 2 weeks prior to enrollment.
  • Must have the clinical capacity to complete at least one 21-day treatment cycle without, in the investigator's judgment, a foreseeable need for prolonged hospitalization related to their underlying disease

Inclusion criteria specific to Part B6:

  • Metastatic or locally advanced PDAC or acinar cell carcinoma with alterations to the ATM gene
  • Participants must have received at least 1 prior chemotherapy regimen for the treatment of the advanced disease OR have received neoadjuvant/adjuvant therapy with recurring occurring <6 months following completion of this treatment.
  • Have at least 1 measurable lesion assessable using standard techniques by RECIST v1.1. Previously irradiated lesions may not be considered target lesions.
  • Serum albumin ≥3g/dL within 7 days prior to first dose.
  • ECOG Performance Status must be stable for at least 2 weeks prior to enrollment.
  • Must have the clinical capacity to complete at least one 21-day treatment cycle without, in the investigator's judgment, a foreseeable need for prolonged hospitalization related to their underlying disease.

General Exclusion Criteria:

  • 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
  • Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks before the first dose of study treatment.
  • A 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

Additional exclusion criteria for participants in dose escalation (Part A3, B1, B5, and B6 in combination with irinotecan):

  • Patients who have symptoms or signs of clinically unacceptable deterioration of the primary disease at the time of screening.
  • Patients who are known to be homozygous for both UGT1A1 \*6 and \*28 (UGT1A1 7/7 genotype), or simultaneously heterozygous for both UGT1A1 \*6 and \*28.
  • Patients receiving strong inhibitors of UGT1A1 within 2 weeks before the first dose of study treatment
  • 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: Neuroendocrine (carcinoid, islet cell) or adenosquamous carcinoma pancreatic cancer
  • Parts B5 and B6: Initiation of opioids in the previous 2 weeks.
  • Parts B5 and B6: Weight loss >10% in the previous 8 weeks.
  • Parts B5 and B6: Active intestinal obstruction, ileus, or significant malabsorption.

Study Design

Enrollment

542 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A1

Part A1 evaluated intermittent and continuous dosing of ART0380 monotherapy. Treatment was given in 21-day cycles.

experimental: Part A2

Part A2 evaluated intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles.

experimental: Part A3

Part A3 evaluated intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles.

experimental: Part B1

In Part B1, up to 8 cohorts enrolled 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 monotherapy Or
  • ART0380 in combination with irinotecan

experimental: Part B2

In Part B2, participants with high grade serous ovarian, primary peritoneal, or fallopian tube carcinoma were randomized (open label) 1:1 to either ART0380 in combination with gemcitabine or gemcitabine alone.

experimental: Part B3

in Part B3, participants with persistent or recurrent endometrial cancer (EC) received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

experimental: Part B4

In Part B4, participants with advanced or metastatic solid tumors received ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

experimental: Part B5

In Part B5, participants with colorectal cancer (CRC) will receive ART0380 in combination with irinotecan on a 21-day cycle.

experimental: Part B6

In Part B6, participants with pancreatic ductal adenocarcinoma (PDAC) or acinar cell carcinoma will receive ART0380 in combination with irinotecan on a 21-day cycle.

experimental: Part A3 Fed/Fast

Part A3 Fed/Fast will evaluate intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles in a fasting or fed state.

Interventions

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.

Gemcitabine

Gemcitabine will be administered on Days 1 and 8 of a 21-day cycle.

Irinotecan

Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.

Primary outcome measure

  • 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 [ Time Frame: From Cycle 0 Day -2 to Cycle 1 Day 21. Each cycle is 21 days. ]
  • Parts B1/B3/B4: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan at RP2Ds. [ Time Frame: 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 [ Time Frame: 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 B5/B6: Object Response Rate (ORR) based on RECIST 1.1 to access anti-tumor activity of ART0380 in combination with irinotecan in each cohort. [ Time Frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Each Cycle is 21 days. ]

Central Contacts and Locations

Central contacts

Sarah Cannon Development Innovations

844-710-6157SCRI.InnovationsMedical@scri.com

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294-3300

Mayo Clinic (Arizona)

Recruiting

Scottsdale, Arizona, United States, 85259

University of Arkansas - Winthrop P. Rockefeller Cancer Institute

Recruiting

Little Rock, Arkansas, United States, 72205

USC Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Sansum Clinic

Recruiting

Santa Barbara, California, United States, 93105

Providence Medical Foundation

Recruiting

Santa Rosa, California, United States, 95403

Rocky Mountain Cancer Center

Recruiting

Denver, Colorado, United States, 80218

Sarah Cannon Research Institute at HealthONE

Recruiting

Denver, Colorado, United States, 80218

Florida Cancer Specialists

Recruiting

Fort Myers, Florida, United States, 33901

Mayo Clinic (Florida)

Recruiting

Jacksonville, Florida, United States, 32224

Cancer Specialists of North Florida

Recruiting

Jacksonville, Florida, United States, 32256

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

Florida Cancer Specialists

Recruiting

West Palm Beach, Florida, United States, 33401

Hope and Healing Cancer Services

Recruiting

Hinsdale, Illinois, United States, 60521

Community Health Network

Recruiting

Indianapolis, Indiana, United States, 46250

Our Lady of the Lake

Recruiting

Baton Rouge, Louisiana, United States, 70808

Maryland Oncology Hematology - Primary

Recruiting

Columbia, Maryland, United States, 21044

Minnesota Oncology Hematology

Recruiting

Maple Grove, Minnesota, United States, 55369

Mayo Clinic (Minnesota)

Recruiting

Rochester, Minnesota, United States, 55905

Washington University

Recruiting

St Louis, Missouri, United States, 63110

Hematology Oncology Associates of Central New York

Recruiting

East Syracuse, New York, United States, 13057

Northwell Health Cancer Institute

Recruiting

Lake Success, New York, United States, 11042

Oncology Hematology Care Primary

Recruiting

Cincinnati, Ohio, United States, 45242

Taylor Cancer Research Center

Recruiting

Maumee, Ohio, United States, 43537

Stephenson Cancer Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Oregon Health & Science University

Recruiting

Portland, Oregon, United States, 97239

University of Pennsylvania / Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Tennessee Oncology, PLLC

Recruiting

Chattanooga, Tennessee, United States, 37404

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Texas Oncology - Central/South Texas

Recruiting

Austin, Texas, United States, 78705

Mary Crowley Cancer Research

Recruiting

Dallas, Texas, United States, 75230

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Recruiting

Dallas, Texas, United States, 75246

Texas Oncology - Northeast Texas

Recruiting

Flower Mound, Texas, United States, 75028

Texas Oncology - San Antonio

Recruiting

San Antonio, Texas, United States, 78240

Utah Cancer Specialists

Recruiting

Salt Lake City, Utah, United States, 84106

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Artios Pharma Ltd

Last update posted

Jul 30, 2026

Last verified

Jul, 2026

Keywords

  • Loss of Ataxia Telangiectasia Mutated (ATM) protein

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Artios Pharma Ltd on 2026-07-30.