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NCT04657068PHASE1, PHASE2Recruiting

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

Artios Pharma Ltd

Start Date

1/27/2021

Completion Date

6/1/2028

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

ART0380

DRUG

Gemcitabine

DRUG

Irinotecan

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Conditions

Advanced CancerMetastatic CancerOvarian CancerPrimary Peritoneal CancerFallopian Tube CancerEndometrial CancerMetastatic Colorectal CancerPancreatic Ductal AdenocarcinomaAcinar Cell Carcinoma

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35294-3300

United States

Mayo Clinic (Arizona)

Scottsdale, Arizona 85259

United States

University of Arkansas - Winthrop P. Rockefeller Cancer Institute

Little Rock, Arkansas 72205

United States

USC Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Sansum Clinic

Santa Barbara, California 93105

United States

Providence Medical Foundation

Santa Rosa, California 95403

United States

Rocky Mountain Cancer Center

Denver, Colorado 80218

United States

Sarah Cannon Research Institute at HealthONE

Denver, Colorado 80218

United States

Florida Cancer Specialists

Fort Myers, Florida 33901

United States

Mayo Clinic (Florida)

Jacksonville, Florida 32224

United States

Cancer Specialists of North Florida

Jacksonville, Florida 32256

United States

Florida Cancer Specialists

Orlando, Florida 32827

United States

Florida Cancer Specialists

Sarasota, Florida 34232

United States

Florida Cancer Specialists

West Palm Beach, Florida 33401

United States

Hope and Healing Cancer Services

Hinsdale, Illinois 60521

United States

Community Health Network

Indianapolis, Indiana 46250

United States

Our Lady of the Lake

Baton Rouge, Louisiana 70808

United States

Maryland Oncology Hematology - Primary

Columbia, Maryland 21044

United States

Minnesota Oncology Hematology

Maple Grove, Minnesota 55369

United States

Mayo Clinic (Minnesota)

Rochester, Minnesota 55905

United States

Washington University

St Louis, Missouri 63110

United States

Hematology Oncology Associates of Central New York

East Syracuse, New York 13057

United States

Northwell Health Cancer Institute

Lake Success, New York 11042

United States

Oncology Hematology Care Primary

Cincinnati, Ohio 45242

United States

Taylor Cancer Research Center

Maumee, Ohio 43537

United States

Stephenson Cancer Center

Oklahoma City, Oklahoma 73104

United States

Oregon Health & Science University

Portland, Oregon 97239

United States

University of Pennsylvania / Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

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

Philadelphia, Pennsylvania 19107

United States

Tennessee Oncology, PLLC

Chattanooga, Tennessee 37404

United States

Baptist Cancer Center

Memphis, Tennessee 38120

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Vanderbilt Medical Center

Nashville, Tennessee 37232

United States

Texas Oncology - Central/South Texas

Austin, Texas 78705

United States

Mary Crowley Cancer Research

Dallas, Texas 75230

United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas 75246

United States

Texas Oncology - Northeast Texas

Flower Mound, Texas 75028

United States

Oncology Consultants

Houston, Texas 77030

United States

Texas Oncology - San Antonio

San Antonio, Texas 78240

United States

Utah Cancer Specialists

Salt Lake City, Utah 84106

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Institut Gustave Roussy

Villejuif, Cedex 94805

France

Institut Bergonie

Bordeau, 33076

France

Marseille University Hospital Timone

Marseille, 13005

France

Saint-Louis Hospital

Paris, 75010

France

Hospital Saint-Antoine

Paris, 75012

France

Hospital de la Pitié-Salpêtrière

Paris, 75013

France

Hospital General Universitario de Elche

Elche, Alicante 03203

Spain

H. Parc Tauli

Sabadell, Barcelona 08208

Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria 39008

Spain

Next Oncology Barcelona, IOB

Barcelona, Catalonia 08023

Spain

Hospital Arnau de Vilanova

Lleida, Catalonia 25198

Spain

Hospital Universitario La Paz

Madrid, Madrid 28046

Spain

Next - Hospital Quironsalud Madrid

Pozuelo de Alarcón, Madrid 28223

Spain

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia 30120

Spain

Clínica Universidad de Navarra

Madrid, Planta -2 28027

Spain

Hospital Clínico Universitario de Santiago (CHUS)

A Coruña, 00000

Spain

Hospital Teresa Herrera (CHUAC)

A Coruña, 15006

Spain

Institut Català d'Oncologia Badalona - Hospital Germans Trias i Pujol

Badalona, 08916

Spain

Vall d'Hebron Institute of Oncology (VIHO)

Barcelona, 08035

Spain

Hospital Clinic de Barcelona

Barcelona, 08036

Spain

ICO Hospitalet

Barcelona, 08903

Spain

Hospital Universitario Reina Sofia de Córdoba

Córdoba, 14004

Spain

Hospital Universitari Doctor Josep Trueta- ICO de Girona

Girona, 17007

Spain

Hospital General Universitario Gregorio Marañón

Madrid, 28007

Spain

MD Anderson Cancer Center (Madrid

Madrid, 28033

Spain

Hospital Clinico San Carlos

Madrid, 28040

Spain

START Madrid Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

START Madrid (Hospital San Chinarro)

Madrid, 28050

Spain

Hospital Universitario Virgen de la Victoria

Málaga, 29010

Spain

Hospital Universitario De Navarra

Pamplona, 31008

Spain

START Rioja

Rioja, 26006

Spain

Hospital Virgen Macarena

Seville, 41009

Spain

Hospital Virgen del Rocío

Seville, 41013

Spain

Instituto Valenciano de Oncología (IVO)

Valencia, 00000

Spain

Incliva Biomedical Research Institute, University of Valencia

Valencia, 46010

Spain

Hospital Universitario Miguel Servet

Zaragoza, 50009

Spain

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN

United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT

United Kingdom

Sarah Cannon Research Institute UK

London, W1G 6AD

United Kingdom

The Christie NHS Foundation Trust - The Christie Clinic

Manchester, M20 4BX

United Kingdom