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

NCT04657068 · Artios Pharma Ltd
In plain English

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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 442 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2021-01-27
Estimated completion: 2027-12
Last updated: 2026-03-18
Interventions
Drug: ART0380Drug: GemcitabineDrug: Irinotecan
Primary outcomes
  • 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: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan at RP2Ds. (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 (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.)
Sponsor
Artios Pharma Ltd · industry
Contacts & investigators
ContactSarah Cannon Development Innovations · contact · SCRI.InnovationsMedical@scri.com · 844-710-6157
InvestigatorMelissa Johnson, MD · study_chair, Tennessee Oncology
InvestigatorAntonio Gonzalez, MD, PHD · study_chair, Clinica Universidad de Navarra, Madrid
InvestigatorSusanna Ulahannan, MD · principal_investigator, Oklahoma University
All locations (79)
University of Alabama at BirminghamRecruiting
Birmingham, Alabama, United States
Mayo Clinic (Arizona)Recruiting
Scottsdale, Arizona, United States
University of Arkansas - Winthrop P. Rockefeller Cancer InstituteRecruiting
Little Rock, Arkansas, United States
USC Norris Comprehensive Cancer CenterRecruiting
Los Angeles, California, United States
Sansum ClinicRecruiting
Santa Barbara, California, United States
Providence Medical FoundationRecruiting
Santa Rosa, California, United States
Rocky Mountain Cancer CenterRecruiting
Denver, Colorado, United States
Sarah Cannon Research Institute at HealthONERecruiting
Denver, Colorado, United States
Florida Cancer SpecialistsRecruiting
Fort Myers, Florida, United States
Mayo Clinic (Florida)Recruiting
Jacksonville, Florida, United States
Cancer Specialists of North FloridaRecruiting
Jacksonville, Florida, United States
Florida Cancer SpecialistsCompleted
Orlando, Florida, United States
Florida Cancer SpecialistsRecruiting
Sarasota, Florida, United States
Florida Cancer SpecialistsRecruiting
West Palm Beach, Florida, United States
Hope and Healing Cancer ServicesRecruiting
Hinsdale, Illinois, United States
Community Health NetworkRecruiting
Indianapolis, Indiana, United States
Our Lady of the LakeRecruiting
Baton Rouge, Louisiana, United States
Maryland Oncology Hematology - PrimaryRecruiting
Columbia, Maryland, United States
Minnesota Oncology HematologyRecruiting
Maple Grove, Minnesota, United States
Mayo Clinic (Minnesota)Recruiting
Rochester, Minnesota, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
Hematology Oncology Associates of Central New YorkRecruiting
East Syracuse, New York, United States
Northwell Health Cancer InstituteRecruiting
Lake Success, New York, United States
Oncology Hematology Care PrimaryRecruiting
Cincinnati, Ohio, United States
Taylor Cancer Research CenterRecruiting
Maumee, Ohio, United States
Stephenson Cancer CenterRecruiting
Oklahoma City, Oklahoma, United States
Oregon Health & Science UniversityRecruiting
Portland, Oregon, United States
University of Pennsylvania / Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research OrganizationRecruiting
Philadelphia, Pennsylvania, United States
Tennessee Oncology, PLLCRecruiting
Chattanooga, Tennessee, United States
Baptist Cancer CenterCompleted
Memphis, Tennessee, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
Texas Oncology - Central/South TexasRecruiting
Austin, Texas, United States
Mary Crowley Cancer ResearchRecruiting
Dallas, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer CenterRecruiting
Dallas, Texas, United States
Texas Oncology - Northeast TexasRecruiting
Flower Mound, Texas, United States
Oncology ConsultantsCompleted
Houston, Texas, United States
Texas Oncology - San AntonioRecruiting
San Antonio, Texas, United States
Utah Cancer SpecialistsRecruiting
Salt Lake City, Utah, United States
Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States
Institut Gustave RoussyRecruiting
Villejuif, Cedex, France
Institut BergonieRecruiting
Bordeau, France
Marseille University Hospital TimoneRecruiting
Marseille, France
Saint-Louis HospitalRecruiting
Paris, France
Hospital de la Pitié-SalpêtrièreRecruiting
Paris, France
Hospital General Universitario de ElcheRecruiting
Elche, Alicante, Spain
H. Parc TauliRecruiting
Sabadell, Barcelona, Spain
Next Oncology Barcelona, IOBRecruiting
Barcelona, Catalonia, Spain
Hospital Arnau de VilanovaRecruiting
Lleida, Catalonia, Spain
Hospital Universitario La PazRecruiting
Madrid, Madrid, Spain
Next - Hospital Quironsalud MadridRecruiting
Pozuelo de Alarcón, Madrid, Spain
Hospital Clínico Universitario Virgen de la ArrixacaRecruiting
El Palmar, Murcia, Spain
Clínica Universidad de NavarraRecruiting
Madrid, Planta -2, Spain
Hospital Clínico Universitario de Santiago (CHUS)Recruiting
A Coruña, Spain
Hospital Teresa Herrera (CHUAC)Recruiting
A Coruña, Spain
Institut Català d'Oncologia Badalona - Hospital Germans Trias i PujolRecruiting
Badalona, Spain
Vall d'Hebron Institute of Oncology (VIHO)Recruiting
Barcelona, Spain
Hospital Clinic de BarcelonaRecruiting
Barcelona, Spain
ICO HospitaletRecruiting
Barcelona, Spain
Hospital Universitario Reina Sofia de CórdobaRecruiting
Córdoba, Spain
Hospital Universitari Doctor Josep Trueta- ICO de GironaRecruiting
Girona, Spain
Hospital General Universitario Gregorio MarañónRecruiting
Madrid, Spain
MD Anderson Cancer Center (MadridRecruiting
Madrid, Spain
Hospital Clinico San CarlosRecruiting
Madrid, Spain
START Madrid Fundacion Jimenez DiazRecruiting
Madrid, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
START Madrid (Hospital San Chinarro)Recruiting
Madrid, Spain
Hospital Universitario Virgen de la VictoriaRecruiting
Málaga, Spain
Hospital Universitario De NavarraRecruiting
Pamplona, Spain
START RiojaRecruiting
Rioja, Spain
Hospital Virgen MacarenaRecruiting
Seville, Spain
Hospital Virgen del RocíoRecruiting
Seville, Spain
Instituto Valenciano de Oncología (IVO)Recruiting
Valencia, Spain
Incliva Biomedical Research Institute, University of ValenciaRecruiting
Valencia, Spain
Hospital Universitario Miguel ServetRecruiting
Zaragoza, Spain
Beatson West of Scotland Cancer CentreRecruiting
Glasgow, United Kingdom
Guy's and St Thomas' NHS Foundation TrustRecruiting
London, United Kingdom
Sarah Cannon Research Institute UKRecruiting
London, United Kingdom
The Christie NHS Foundation Trust - The Christie ClinicRecruiting
Manchester, United Kingdom
A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors · TrialPath