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

A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients With 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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer; Ovarian Cancer; Fallopian Tube Cancer; Metastatic Cancer; Endometrial Cancer; Advanced Cancer; Primary Peritoneal Cancer; Pancreatic Ductal Adenocarcinoma; Acinar Cell Carcinoma
• Intervention / Treatment: Drug: ART0380; Drug: Irinotecan; Drug: Gemcitabine

Detailed Description

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), and high grade serous ovarian, primary peritoneal or fallopian tube carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 442
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sarah Cannon Development Innovations; Phone Number: 844-710-6157; Email: SCRI.InnovationsMedical@scri.com

Study Locations

• France
  • Bordeau, France, 33076
    • Recruiting
    • Institut Bergonié
  • Marseille, France, 13005
    • Recruiting
    • Marseille University Hospital Timone
  • Paris, France, 75010
    • Recruiting
    • Saint-Louis Hospital
  • Paris, France, 75013
    • Recruiting
    • Hospital de la Pitie-Salpetriere
  • Cedex
    • Villejuif, Cedex, France, 94805
      • Recruiting
      • Institut Gustave Roussy
      • Contact: Capucine Baldini, MD
• Spain
  • A Coruña, Spain, 15006
    • Recruiting
    • Hospital Teresa Herrera (CHUAC)
  • A Coruña, Spain, 00000
    • Recruiting
    • Hospital Clínico Universitario de Santiago (CHUS)
  • Badalona, Spain, 08916
    • Recruiting
    • Institut Català d'Oncologia Badalona - Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08903
    • Recruiting
    • ICO Hospitalet
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d'Hebron Institute of Oncology (VIHO)
    • Principal Investigator: Elena Elez
  • Córdoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofía de Córdoba
  • Girona, Spain, 17007
    • Recruiting
    • Hospital Universitari Doctor Josep Trueta- ICO de Girona
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28040
    • Recruiting
    • Start Madrid Fundacion Jimenez Diaz
  • Madrid, Spain, 28033
    • Recruiting
    • MD Anderson Cancer Center (Madrid
  • Madrid, Spain, 28050
    • Recruiting
    • START Madrid (Hospital San Chinarro)
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
  • Pamplona, Spain, 31008
    • Recruiting
    • Hospital Universitario de Navarra
  • Rioja, Spain, 26006
    • Recruiting
    • START Rioja
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Virgen del Rocío
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Virgen Macarena
  • Valencia, Spain, 46010
    • Recruiting
    • Incliva Biomedical Research Institute, University of Valencia
  • Valencia, Spain, 00000
    • Recruiting
    • Instituto Valenciano de Oncología (IVO)
  • Zaragoza, Spain, 50009
    • Recruiting
    • Hospital Universitario Miguel Servet
    • Principal Investigator: Sara Perez
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Recruiting
      • Hospital General Universitario de Elche
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Recruiting
      • H. Parc Tauli
  • Catalonia
    • Barcelona, Catalonia, Spain, 08023
      • Recruiting
      • Next Oncology Barcelona, IOB
    • Lleida, Catalonia, Spain, 25198
      • Recruiting
      • Hospital Arnau de Vilanova
  • Madrid
    • Madrid, Madrid, Spain, 28046
      • Recruiting
      • Hospital Universitario La Paz
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Recruiting
      • Next - Hospital Quironsalud Madrid
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clínico Universitario Virgen de la Arrixaca
  • Planta -2
    • Madrid, Planta -2, Spain, 28027
      • Recruiting
      • Clinica Universidad de Navarra
      • Principal Investigator: Jorge Bartolome
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
    • Principal Investigator: Elisa Fontana
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: Rebecca S. Kristeleit, MD
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust - The Christie Clinic
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • Recruiting
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic (Arizona)
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas - Winthrop P. Rockefeller Cancer Institute
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC Norris Comprehensive Cancer Center
    • Santa Barbara, California, United States, 93105
      • Recruiting
      • Sansum Clinic
    • Santa Rosa, California, United States, 95403
      • Recruiting
      • Providence Medical Foundation
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute at HealthONE
      • Principal Investigator: Gerald Falchook, MD
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Rocky Mountain Cancer Center
      • Principal Investigator: Manojkumar Bupathi
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Fadi Kayali, MD
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Cancer Specialists of North Florida
      • Principal Investigator: Gaurav Trikha, MD
      • Contact: Gaurav Trikha; Phone Number: 904-825-4500; Email: Gaurav.Trikha@CSNF.us
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic (Florida)
    • Orlando, Florida, United States, 32827
      • Completed
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Manish Patel, MD
    • West Palm Beach, Florida, United States, 33401
      • Recruiting
      • Florida Cancer Specialists
      • Principal Investigator: Barry Scott Berman, MD
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Hope and Healing Cancer Services
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Recruiting
      • Community Health Network
      • Principal Investigator: Bert O'Neil
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Our Lady of The Lake
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Maryland Oncology Hematology - Primary
  • Minnesota
    • Maple Grove, Minnesota, United States, 55369
      • Recruiting
      • Minnesota Oncology Hematology
      • Contact: Sandeep Jain, MBBS; Phone Number: 763-712-2100; Email: Sandeep.Jain@usoncology.com
      • Principal Investigator: Sandeep Jain, MBBS
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic (Minnesota)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • New York
    • East Syracuse, New York, United States, 13057
      • Recruiting
      • Hematology Oncology Associates of Central New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Oncology Hematology Care Primary
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Taylor Cancer Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Stephenson Cancer Center
      • Principal Investigator: Kathleen Moore, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
      • Principal Investigator: Babar Bashir, MD
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania / Abramson Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Tennessee Oncology, PLLC
      • Principal Investigator: Edward Riker Arrowsmith, MD
    • Memphis, Tennessee, United States, 38120
      • Completed
      • Baptist Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
      • Principal Investigator: Melissa Johnson, MD
  • Texas
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Oncology - Central/South Texas
      • Contact: Marco Araneda, MD; Phone Number: 956-425-8845; Email: Marco.araneda@usoncology.com
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
      • Principal Investigator: Scott Paulson
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
      • Principal Investigator: Minal Barve, MD
    • Flower Mound, Texas, United States, 75028
      • Recruiting
      • Texas Oncology - Northeast Texas
    • Houston, Texas, United States, 77030
      • Completed
      • Oncology Consultants
    • San Antonio, Texas, United States, 78240
      • Recruiting
      • Texas Oncology - San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Recruiting
      • Utah Cancer Specialists
      • Principal Investigator: Stephan Kendall
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 and have demonstrated progressive disease or intolerance to their last regimen.

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 a maximum of 1 prior chemotherapy regimen for the treatment of the advanced disease and have demonstrated progressive disease or intolerance to this regimen 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A1; Part A1 evaluated intermittent and continuous dosing of ART0380 monotherapy. Treatment was given in 21-day cycles.	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 evaluated intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles.	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.; Other Names: Gemzar
Experimental: Part A3; Part A3 evaluated intermittent dosing of ART0380 in combination with irinotecan in 21-day cycles.	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.; Other Names: Camptosar; Camptothecin-11
Experimental: Part B1; In Part B1, up to 7 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	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.; Other Names: Camptosar; Camptothecin-11
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.	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.; Other Names: Gemzar
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.	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, 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.	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, 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.; Other Names: Camptosar; Camptothecin-11
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.	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.; Other Names: Camptosar; Camptothecin-11
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.	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.; Other Names: Camptosar; Camptothecin-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.
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.
Parts B1/B3/B4: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan at RP2Ds.	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.
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.	Objective Response Rate (ORR)	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.

Secondary Outcome Measures

Outcome Measure	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.
Parts A1, A2, A3, B1, B3, B4: 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.
Part B5/B6: Number of participants with adverse events following administration of ART0380 at the RP2D in combination with irinotecan.	From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or irinotecan. Each cycle is 21 days.
Pharmacokinetic Analysis (single and multiple dose): Renal clearance of ART0380	Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.
Pharmacokinetic Analysis (single dose): Maximum plasma Concentration (Cmax) in a fasting and fed state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (single dose): 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 (single dose): 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 (single dose): Area Under the Curve Plasma Concentration Time Curve from zero to 24 hours (AUC0-24) in a fasting and fed state	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (single dose): 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 (single dose): Area Under The Curve Plasma Concentration Time Curve from zero to 12 hours (AUC0-12) in a fasting and fed state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (single dose): 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 (single dose): 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 (single dose): 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
Pharmacokinetic Analysis (multiple dose): Maximum plasma Concentration (Cmax ss) once steady sate has been reached.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Time to Maximum plasma concentration (Tmax ss) at steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Time to lowest plasma concentration (Cmin ss) at steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Terminal half-life (t1/2 ss) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Area Under The Curve Plasma Concentration Time Curve from zero to the time of last plasma concentration (AUC0-t ss) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Area Under The Curve Plasma Concentration Time Curve from zero to 12 hours (AUC0-12 ss) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Area Under the Curve Plasma Concentration Time Curve from zero to 24 hours (AUC0-24 ss) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Area Under the Curve Plasma Concentration Time (AUC ss) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis (multiple dose): Area under the concentration-time curve for Oral Clearance (CL ss/F) in a steady state.	PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: The geometric mean ratio (GMR) and associated 90% confidence interval (Cl) for 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: The geometric mean ratio (GMR) and associated 90% confidence interval (Cl) for the maximum plasma concentration (Cmax) in a fasting and fed state.	PK will be measured during Cycle 1. Cycle 1 is 21 days.
Pharmacokinetic Parameters: Accumulation Rate (Rac) of increase in drug concentration in the body after repeated dosing compared to a single dose.	PK will be measured during Cycle 1. Cycle 1 is 21 days.
Pharmacokinetic Analysis: Urine concentration data following single and multiple oral dosing in monotherapy.	Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.
Pharmacokinetic Analysis: Hodges-Lehmann estimate of median difference in tmax and associated 90% CI in a fasted and fed state.	PK will be measured during Cycle 1. Cycle 1 is 21 days.
Parts B1/B3/B4/B5/B6: Response and disease progression by Serological tumor markers (CA-19-9, CAE, CA-125, and Prostate Specific Antigen (PSA)).	Tumor markers will be measured for 18 weeks, then every 9 weeks thereafter.
Parts A1, A2, A3, B1, 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, 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.
Parts B1/B3/B4/B5/B6: Overall Survival	After first dose through PFS/OS follow-up.

Collaborators and Investigators

• Sponsor: Artios Pharma Ltd
• Investigators: Study Chair: Melissa Johnson, MD, Tennessee Oncology; Study Chair: Antonio Gonzalez, MD, PHD, Clínica Universidad de Navarra, Madrid; Principal Investigator: Susanna Ulahannan, MD, Oklahoma University; Principal Investigator: Kim Reiss Binder, MD, University of Pennsylvania / Abramson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Loss of Ataxia Telangiectasia Mutated (ATM) protein
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Nervous System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neuromuscular Diseases; Genetic Diseases, Inborn; Intestinal Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neurodegenerative Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Neoplastic Processes; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Uterine Neoplasms; Nervous System Malformations; Fallopian Tube Diseases; Polyneuropathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Ovarian Neoplasms; Neoplasm Metastasis; Endometrial Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Acinar Cell; Hereditary Sensory and Autonomic Neuropathies; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Irinotecan; Gemcitabine
• Other Study ID Numbers: ART0380C001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No